JAMA | Review
Medications for Obesity A Review
JAMA | 評論肥胖藥物的回顧

Kimberly A. Gudzune, MD, MPH; Robert F. Kushner, MD, MS
金伯莉·A·古茲恩，醫學博士，公共衛生碩士；羅伯特·F·庫什納，醫學博士，碩士

Abstract 摘要

IMPORTANCE Obesity affects approximately 19% of women and 14% of men worldwide and is associated with increased morbidity. Antiobesity medications (AOMs) modify biological processes that affect appetite and significantly improve outcomes, such as type 2 diabetes, hypertension, and dyslipidemia
重要性肥胖影響全球約 19%的女性和 14%的男性，並與增加的發病率相關。抗肥胖藥物（AOMs）改變影響食慾的生物過程，並顯著改善結果，如 2 型糖尿病、高血壓和血脂異常。

OBSERVATIONS AOMs should be administered in combination with lifestyle interventions and can be classified according to their mechanisms of action. Orlistat modifies digestive tract absorption and causes gastrointestinal adverse effects, such as oily fecal spotting and urgency, in more than $25 %$ of patients. Centrally acting drugs, such as phentermine-topiramate and naltrexone-bupropion, regulate appetite in the brain and are associated with constipation in approximately $20 %$ of patients, although the incidence of other adverse effects (eg, paresthesia, nausea) varies by medication. Nutrient-stimulated hormone-based medications, such as liraglutide, semaglutide, and tirzepatide, mimic the actions of enteropancreatic hormones that modify central appetite regulation and provide multiple cardiometabolic weight-loss benefits. Adverse effects of these drugs include nausea (28%-44%), diarrhea (21%-30%), and constipation (11%-24%). The relative potency of adult obesity medications has been studied in meta-analyses. Compared with placebo, orlistat was associated with 3.1% greater weight loss (52 randomized clinical trials [RCTs]; 16964 participants), phentermine-topiramate was associated with $8.0 %$ greater weight loss ( 5 RCTs; 3407 participants), naltrexone-bupropion was associated with $4.1 %$ greater weight loss (6 RCTs; 9949 participants), liraglutide was associated with 4.7% greater weight loss (18 RCTs; 6321 participants), semaglutide was associated with $11.4 %$ greater weight loss ( 5 RCTs; 4421 participants), and tirzepatide 15 mg was associated with $12.4 %$ greater weight loss (6 RCTs; 1972 participants).
觀察結果 AOMs 應與生活方式干預結合使用，並可根據其作用機制進行分類。奧利司他改變消化道的吸收，並在超過 $25 %$ 的患者中引起腸胃不良反應，如油性糞便斑點和急迫感。中樞作用藥物，如芬特明-托吡酯和納曲酮-布普洛尼，調節大腦中的食慾，並在約 $20 %$ 的患者中與便秘相關，儘管其他不良反應（例如，感覺異常、噁心）的發生率因藥物而異。基於營養刺激激素的藥物，如利拉魯肽、塞馬魯肽和替戈肽，模仿改變中樞食慾調節的腸胰激素的作用，並提供多種心代謝減重益處。這些藥物的不良反應包括噁心（28%-44%）、腹瀉（21%-30%）和便秘（11%-24%）。成人肥胖藥物的相對效力已在綜合分析中進行研究。與安慰劑相比，奧利司他與 3.1%的體重減輕相關（52 項隨機臨床試驗[RCTs]；16964 名參與者），芬特明-托吡酯與 $8.0 %$ 的體重減輕相關（5 項 RCTs；3407 名參與者），納曲酮-布普洛尼與 $4.1 %$ 的體重減輕相關（6 項 RCTs；9949 名參與者），利拉魯肽與 4.7%的體重減輕相關（18 項 RCTs；6321 名參與者），塞馬魯肽與 $11.4 %$ 的體重減輕相關（5 項 RCTs；4421 名參與者），而提澤帕肽 15 毫克與 $12.4 %$ 的體重減輕相關（6 項 RCTs；1972 名參與者）。

CONCLUSION AND RELEVANCE Obesity is associated with increased morbidity. Antiobesity medications are effective adjunctive therapy to lifestyle changes for improved weight loss and health outcomes.
結論與相關性肥胖與增加的發病率有關。抗肥胖藥物是改善體重減輕和健康結果的有效輔助療法，與生活方式改變相結合。

JAMA. doi:10.1001/jama.2024.10816
Published online July 22, 2024.
於 2024 年 7 月 22 日在線發佈。

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Author Affiliations: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland (Gudzune); Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Gudzune); Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois (Kushner); Department of Medical Education, Northwestern University Feinberg School of Medicine, Chicago, Illinois (Kushner).
作者隸屬機構：馬里蘭州巴爾的摩約翰霍普金斯大學醫學院內科系（Gudzune）；馬里蘭州巴爾的摩約翰霍普金斯布隆伯格公共衛生學院健康政策與管理系（Gudzune）；伊利諾伊州芝加哥西北大學芬伯格醫學院內科系（Kushner）；伊利諾伊州芝加哥西北大學芬伯格醫學院醫學教育系（Kushner）。
Corresponding Author: Robert F. Kushner, MD, MS, 645 N Michigan Ave, Ste 530, Chicago, IL 60611 (rkushner@northwestern.edu).
通訊作者：羅伯特·F·庫什納，醫學博士，碩士，645 N 密歇根大道，530 室，芝加哥，IL 60611（rkushner@northwestern.edu）。
Section Editor: Kristin Walter, MD, Deputy Editor.
編輯部主任：克里斯汀·沃爾特醫生，副編輯。

Obesity is a global public health problem associated with an increased prevalence of multiple chronic conditions compared with individuals without obesity.

^{1}

Since 1999, the prevalence of obesity among adults, defined as a body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 30 or greater, has risen from

30 %

42 %

in the US and is projected to affect nearly 1 in 2 adults by

2030 .^{2}

Worldwide, obesity now affects

19 %

of women and

14 %

of men.

^{3}

Lifestyle management is important for obesity treatment, but is often associated with weight regain due to counterregulatory physiologic changes that impair metabolism and increase appetite.

^{4}

Antiobesity medications (AOMs) affect appetite dysregulation associated with obesity, thereby achieving and sustaining greater weight loss.

^{5}

Multiple obesity treatment guidelines recommend pharmacotherapy in conjunction with lifestyle modification.

^{6 - 10}

The US Food and Drug Administration (FDA) has approved multiple AOMs,
肥胖是一個全球公共健康問題，與多種慢性疾病的發病率增加有關，與沒有肥胖的個體相比。自 1999 年以來，在美國，肥胖的盛行率（定義為體重指數（BMI，計算方式為體重（公斤）除以身高（米）的平方）為 30 或更高）已從

30 %

上升至

42 %

，並預計到

2030 .^{2}

將影響近一半的成年人。全球範圍內，肥胖現在影響

19 %

的女性和

14 %

的男性。生活方式管理對於肥胖治療至關重要，但通常與體重反彈有關，這是由於反調節生理變化影響新陳代謝並增加食慾。抗肥胖藥物（AOMs）影響與肥胖相關的食慾失調，從而實現並維持更大的體重減輕。多項肥胖治療指南建議將藥物治療與生活方式改變結合使用。美國食品和藥物管理局（FDA）已批准多種 AOMs，
which are indicated for adults with a BMI of 30 or greater or for adults with a BMI of 27 or greater with weight-related comorbidities, such as type 2 diabetes, hypertension, or dyslipidemia.

^{6 - 9}

AOMs are also indicated for adolescents (aged

\geq 12

years) with BMI at or above the 95th percentile for age and sex.

^{10}

Insufficient evidence exists for AOM use in children younger than 12 years.

^{10}

Because adults of Asian and Southeast Asian ancestry experience obesity-related complications at lower BMIs, lower thresholds may be considered for AOM initiation in this population (BMI

\geq 27

or BMI

\geq 25

with weight-related comorbidities).

^{11}

This review summarizes the efficacy and safety of AOMs. Currently available AOMs are presented in 3 groups based on their mechanisms of action: intragastrointestinal medications (orlistat), centrally acting medications (phentermine, phentermine-topiramate, naltrexone-bupropion), and nutrient-stimulated hormone-based medications (liraglutide, semaglutide, tirzepatide) (Figure 1).
適用於 BMI 為 30 或更高的成年人，或 BMI 為 27 或更高且有與體重相關的合併症（如 2 型糖尿病、高血壓或血脂異常）的成年人。

^{6 - 9}

AOM 也適用於 BMI 達到或超過年齡和性別的第 95 百分位數的青少年（年齡

\geq 12

歲）。

^{10}

對於 12 歲以下的兒童，AOM 的使用證據不足。

^{10}

由於亞洲和東南亞血統的成年人在較低的 BMI 下會出現與肥胖相關的併發症，因此在這一人群中，AOM 啟動的 BMI 閾值可以考慮降低（BMI

\geq 27

或 BMI

\geq 25

且有與體重相關的合併症）。

^{11}

本評估總結了 AOM 的療效和安全性。目前可用的 AOM 根據其作用機制分為三組：腸內藥物（奧利司他）、中樞作用藥物（芬特明、芬特明-托吡酯、納曲酮-布普品）和營養刺激激素基藥物（利拉魯肽、塞馬魯肽、提澤帕肽）（圖 1）。

Figure 1. Mechanisms of Action and Common Adverse Effects of 3 Classes of Antiobesity Medication
圖 1. 三類抗肥胖藥物的作用機制及常見不良反應

AMPA indicates a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; GABA,

γ

-aminobutyric acid; GIP, glucose-dependent insulinotropic polypeptide GLP-1, glucagon-like peptide 1.
AMPA 表示 α-氨基-3-羥基-5-甲基-4-異噁唑丙酸；GABA，

γ

-氨基丁酸；GIP，葡萄糖依賴性胰島素促進多肽 GLP-1，胰高血糖素樣肽 1。

Methods 方法

A literature search of PubMed was conducted between January 1, 2015, and February 27, 2024, using the following search terms: antiobesity agents, obesity drug therapy, and obesity pharmacotherapy. The search was limited to randomized clinical trials (RCTs), systematic reviews, and practice guidelines. A total of 744 articles were identified and 88 were included, consisting of 6 clinical practice guidelines, 5 systematic reviews, 4 meta-analyses, 43 RCTs, 9
在 2015 年 1 月 1 日至 2024 年 2 月 27 日之間，對 PubMed 進行了文獻搜索，使用的搜索詞包括：抗肥胖劑、肥胖藥物治療和肥胖藥物療法。搜索限制於隨機對照試驗（RCTs）、系統評價和實踐指導。共識別出 744 篇文章，並納入 88 篇，其中包括 6 項臨床實踐指導、5 項系統評價、4 項荟萃分析、43 項 RCT 和 9 項
observational studies, 17 reviews, 2 study designs/baseline trial data, 2 secondary analyses of trial data, 1 consensus statement, and 3 perspectives (the systematic reviews and meta-analyses were not mutually exclusive).
觀察性研究、17 篇評論、2 種研究設計/基線試驗數據、2 項試驗數據的次級分析、1 份共識聲明，以及 3 個觀點（系統評價和統合分析並不互相排斥）。

Intragastrointestinal Medications
腸胃內用藥物

Currently, only 1FDA-approved AOM, orlistat, works by blocking fat absorption in the gastrointestinal (GI) tract. In the lumen of the stomach and small intestine, orlistat forms a covalent bond with the active site of intestinal lipases, blocking digestion and absorption of
目前，唯一獲得 FDA 批准的 AOM，奧利司他，通過阻止脂肪在胃腸道（GI）中的吸收來發揮作用。在胃和小腸的腔內，奧利司他與腸道脂肪酶的活性位點形成共價鍵，阻止消化和吸收。

Figure 2. Percentage of Adults With Obesity Without Diabetes Achieving Specific Weight-Loss Targets by Antiobesity Medication
圖 2. 無糖尿病的成人中，使用抗肥胖藥物達成特定減重目標的比例

Observed percentages of adult participants with overweight/obesity and without diabetes from randomized clinical trials who achieved categorical body weight reductions of at least

5 %, 10 %, 15 %, 20 %

, and

25 %

from baseline while taking the study drug. Results from 1 trial for the following antiobesity medications are presented: orlistat 120 mg 3 times daily ( 52 weeks),

^{16}

phentermine-topiramate

15 / 92 mg

daily ( 56 weeks),

^{17}

naltrexone-bupropion
觀察到的成年參與者中，超重/肥胖且無糖尿病的百分比來自隨機臨床試驗，這些參與者在服用研究藥物期間實現了至少

5 %, 10 %, 15 %, 20 %

和

25 %

的體重減少。以下抗肥胖藥物的 1 項試驗結果如下：奧利司他 120 毫克每日 3 次（52 週），

^{16}

苯丁胺-托吡酯

15 / 92 mg

每日（56 週），

^{17}

納曲酮-布普洛尼。

32/360 mg total daily dose ( 56 weeks).,

^{18}

liraglutide 3.0 mg daily ( 56 weeks),

^{19}

semaglutide 2.4 mg weekly ( 68 weeks),

^{20}

and tirzepatide 15 mg weekly ( 72 weeks).

^{21}

No long-term clinical trials are available for phentermine. No data were reported for

\geq 15 %

\geq 25 %

weight reduction for orlistat;

\geq 20 %

\geq 25 %

weight reduction for phentermine-topiramate, naltrexone-bupropion, and liraglutide; or

\geq 25 %

weight reduction for semaglutide.
32/360 毫克每日總劑量（56 週）。

^{18}

利拉魯肽 3.0 毫克每日（56 週），

^{19}

塞馬魯肽 2.4 毫克每週（68 週），

^{20}

以及替爾帕肽 15 毫克每週（72 週）。

^{21}

目前沒有關於芬特明的長期臨床試驗。對於

\geq 15 %

或

\geq 25 %

奧利司他減重的數據未報告；

\geq 20 %

或

\geq 25 %

芬特明-托吡酯、納曲酮-布普利昂和利拉魯肽的減重；或

\geq 25 %

塞馬魯肽的減重數據。
approximately

30 %

of dietary fat, leading to a caloric deficit.

^{12}

A separate treatment, cellulose-citric acid hydrogel, is administered like an oral medication and after ingestion, expands to occupy

25 %

of the stomach’s volume, promoting a sensation of fullness and increased satiety.

^{13}

This hydrogel was FDA-cleared as a device (manufacturers pursue clearance if the device is similar to other legally marketed devices, which differs from approval).

^{14}

大約

30 %

的膳食脂肪，導致熱量赤字。

^{12}

另一種治療，纖維素-檸檬酸水凝膠，像口服藥物一樣給予，並在攝入後膨脹以佔據

25 %

的胃部容量，促進飽腹感和增加飽足感。

^{13}

此水凝膠已獲得 FDA 批准作為一種設備（製造商在設備與其他合法銷售的設備相似時會追求批准，這與認可不同）。

^{14}

Orlistat 奧利司他

Orlistat has been approved for adults since 1999 and for adolescents since 2003. Although most guidelines support its use in treating obesity in adults or adolescents,

^{6 - 8, 10}

the American Gastroenterological Association (AGA) guidelines recommended against orlistat due to its small effect on weight loss and adverse Gl effects.

^{9}

A meta-analysis of 52 RCTs that included 16964 participants reported that orlistat was associated with

3.1 %

greater weight reduction than placebo (

95 % Cl, 2.7 % - 3.5 %

) among adults with obesity.

^{15}

Nearly 70% of orlistat participants achieved 5% or greater weight loss (Figure 2),

^{16 - 21}

and adolescents had significant decreases in BMI (eTable 1 in the Supplement).

^{22}

奧利司他自 1999 年起已獲得成人使用的批准，並自 2003 年起獲得青少年使用的批准。雖然大多數指導方針支持其用於治療成人或青少年的肥胖，

^{6 - 8, 10}

美國胃腸病學會（AGA）指導方針卻建議不使用奧利司他，因為其對減重的效果微小且有不良的腸胃道影響。

^{9}

一項包含 16964 名參與者的 52 項隨機對照試驗的綜合分析報告顯示，奧利司他與

3.1 %

安慰劑相比，在肥胖成人中與體重減輕有關（

95 % Cl, 2.7 % - 3.5 %

）。

^{15}

近 70%的奧利司他參與者達到了 5%或更高的體重減輕（圖 2），

^{16 - 21}

而青少年則在 BMI 上有顯著下降（補充資料中的 eTable 1）。

^{22}

Orlistat reduced waist circumference by approximately 10 cm , systolic blood pressure (SBP) by approximately 6 mm Hg , and lowdensity lipoprotein cholesterol (LDL-C) by approximately 9% among adults with obesity (Table 1).

^{16, 23 - 29}

Among patients with hypertension, a meta-analysis of 4 RCTs that included 2058 participants reported that orlistat was associated with 2.6 mm Hg greater decrease in SBP compared with placebo (

95 % Cl, 1.4 - 3.8

^{30}

In a 4 -year RCT, orlistat was associated with a

37.3 %

lower risk of incident type 2 diabetes compared with placebo (absolute 4 -year incidence of type 2 diabetes: orlistat,

6.2 %

; placebo,

9.0 %

^{23}

In a meta-analysis of 7 RCTs that included 1363 patients with type 2 diabetes, orlistat was associated with 2.0 kg greater weight loss (

95 %

Cl, 1.3 - 2.8

) and

0.5 %

greater hemoglobin

A_{1 c}

reduction (

95 % Cl

,
奧利司他在肥胖成人中使腰圍減少約 10 厘米，收縮壓（SBP）減少約 6 毫米汞柱，低密度脂蛋白膽固醇（LDL-C）減少約 9%（表 1）。在高血壓患者中，一項包含 2058 名參與者的 4 項隨機對照試驗（RCT）荟萃分析報告顯示，奧利司他與安慰劑相比，SBP 的減少量大約多了 2.6 毫米汞柱。在一項為期 4 年的隨機對照試驗中，奧利司他與安慰劑相比，發生 2 型糖尿病的風險降低（4 年內 2 型糖尿病的絕對發生率：奧利司他，；安慰劑，）。在一項包含 1363 名 2 型糖尿病患者的 7 項隨機對照試驗的荟萃分析中，奧利司他與安慰劑相比，體重減輕多了 2.0 公斤，且血紅蛋白減少更多。

0.3 % - 0.6 %

) than placebo.

^{31} An RCT

to test the effects of orlistat on cardiovascular events has not been completed.

0.3 % - 0.6 %

) 比安慰劑更好。

^{31} An RCT

測試奧利司他對心血管事件的影響尚未完成。

Despite its modest effects on weight loss, orlistat typically has cardiometabolic benefits, including lowering SBP, hemoglobin

A_{1 c}

, and LDL-C. Orlistat is also associated with prevention of type 2 diabetes. Orlistat may be most appropriate for patients who would benefit from the cardiometabolic effects of orlistat but do not tolerate or have contraindications to other AOMs (Table 2).

^{12, 25 - 29, 32 - 38}

However, adherence to orlistat has been poor. In a large US health system, no patients prescribed orlistat continued to take the drug after 12 months.

^{39}

Reasons for orlistat discontinuation were not reported.

^{39}

儘管奧利司他對減重的效果有限，但通常具有心代謝益處，包括降低收縮壓、血紅蛋白

A_{1 c}

和低密度脂蛋白膽固醇。奧利司他還與預防 2 型糖尿病相關。奧利司他可能最適合那些能從奧利司他的心代謝效益中受益，但無法耐受或對其他抗肥胖藥物有禁忌的患者（表 2）。

^{12, 25 - 29, 32 - 38}

然而，對奧利司他的依從性一直很差。在美國一個大型健康系統中，沒有患者在 12 個月後繼續服用奧利司他。

^{39}

奧利司他停藥的原因未被報告。

^{39}

Gl adverse effects, including oily fecal spotting (27%), fecal urgency (

22 %

), and steatorrhea (

20 %

), are common in the first year of orlistat use, but typically resolve within 4 weeks

^{12}

and can be reduced by adhering to a low-calorie diet with less than

30 %

of calories from fat (Table 3).

^{12, 40}

Because of its mechanism of action, orlistat should be administered with meals containing some fat (10%

30 %

of calories) to be effective and limit adverse effects.
胃腸道不良反應，包括油性糞便斑點（27%）、糞便急迫感（

22 %

）和脂肪瀉（

20 %

），在使用奧利司他的一年內很常見，但通常在 4 週內會解決

^{12}

，並且可以通過遵循低熱量飲食來減少，該飲食中來自脂肪的熱量少於

30 %

（表 3）。

^{12, 40}

由於其作用機制，奧利司他應與含有一定脂肪的餐食（10%

30 %

的熱量）一起服用，以達到效果並限制不良反應。

Cellulose-Citric Acid Hydrogel
纖維素-檸檬酸水凝膠

Cellulose-citric acid hydrogel was FDA-cleared for adults in 2019.

^{13}

AGA guidelines stated that there was insufficient evidence to recommend its use.

^{9}

In a 24 -week RCT, compared with placebo, the hydrogel achieved

2.1 %

greater mean weight loss and GI adverse effects were common (43%).

^{41}

Product availability is unclear because the manufacturer filed for bankruptcy in October 2023.
纖維素-檸檬酸水凝膠於 2019 年獲得 FDA 批准用於成人。

^{13}

AGA 指導方針指出，沒有足夠的證據來推薦其使用。

^{9}

在一項為期 24 週的隨機對照試驗中，與安慰劑相比，該水凝膠實現了

2.1 %

更大的平均體重減輕，且腸胃不良反應很常見（43%）。

^{41}

產品的可用性不明，因為製造商於 2023 年 10 月申請破產。

Centrally Acting Medications
中樞作用藥物

FDA-approved AOMs that act on the central nervous system include phentermine, phentermine-topiramate, and naltrexonebupropion. These medications have various mechanisms of action in the brain. Combination regimens, such as phenterminetopiramate and naltrexone-bupropion, were developed to provide
FDA 批准的作用於中樞神經系統的 AOM 包括芬特明、芬特明-托吡酯和納曲酮-布普洛尼。這些藥物在大腦中具有不同的作用機制。組合療法，如芬特明-托吡酯和納曲酮-布普洛尼，旨在提供

Table 1. Weight and Cardiovascular Risk Factor Outcomes

^{a}

of Antiobesity Medications in Adults With Obesity and Without Diabetes by Mechanism of Action
表 1. 抗肥胖藥物在有肥胖且無糖尿病的成年人中按作用機制的體重和心血管風險因素結果

^{a}

complementary effects to enhance weight loss. Phentermine is a sympathomimetic amine that primarily increases norepinephrine in the hypothalamus with lesser effects on dopamine and serotonin.

^{42}

Although other sympathomimetic adrenergic agents are available
輔助效果以增強減重。苯丁胺是一種交感神經興奮劑胺，主要在下視丘中增加去甲腎上腺素，對多巴胺和血清素的影響較小。

^{42}

雖然還有其他交感神經興奮劑可用
(eg, diethylpropion), this review focuses only on phentermine because it is the most commonly used AOM in this category of drugs.

^{43, 44}

Information about phentermine may not apply to other sympathomimetics, such as diethylpropion or benzphetamine.

^{45}

（例如，二乙基丙酮），本評論僅專注於芬特明，因為它是這類藥物中最常用的 AOM。

^{43, 44}

有關芬特明的信息可能不適用於其他交感神經興奮劑，如二乙基丙酮或苯氟胺。

^{45}

Table 2. Individualizing Selection of Antiobesity Medications Among Specific Populations With Obesity Common in Primary Care Settings

^{a}

表 2. 在初級護理環境中針對特定肥胖人群個性化選擇抗肥胖藥物

Abbreviations: BP, blood pressure; CAD, coronary artery disease; eGFR, estimated glomerular filtration rate; FDA, US Food and Drug Administration; HR, heart rate; HTN, hypertension.
縮寫：BP，血壓；CAD，冠狀動脈疾病；eGFR，估計腎小球過濾率；FDA，美國食品藥品監督管理局；HR，心率；HTN，高血壓。

^{a}

Guidelines from the American Association of Clinical Endocrinologists/ American College of Endocrinology and Obesity Canada suggest preferred antiobesity medications to use in certain patient populations,

^{7, 8}

which have been adapted for use in this table, along with information from package inserts and recent clinical trials. Specific medications are suggested for use in certain patient populations based on mechanisms of action, organ clearance, weight loss efficacy, adverse effects, warnings and contraindications, and available data for use of the medication within each population. Suggested use should not be interpreted to indicate FDA approval to treat the condition (eg, orlistat is not approved to treat HTN).

^{a}

美國內分泌學會/美國內分泌學與肥胖學會的指導方針建議在某些患者群體中使用首選的抗肥胖藥物，

^{7, 8}

這些建議已被調整以用於本表格，並附有包裝插頁和最近臨床試驗的信息。根據作用機制、器官清除、減重效果、不良反應、警告和禁忌症，以及在每個群體中使用該藥物的可用數據，建議在某些患者群體中使用特定藥物。建議的使用不應被解釋為 FDA 批准治療該病症（例如，奧利司他並未獲得批准用於治療高血壓）。

^{b}

Suggestions applicable to patients with moderate kidney impairment (eGFR

^{b}

適用於中度腎功能不全患者的建議 (eGFR

30 - 49 mL / \min

). For patients with severe kidney impairment (eGFR

< 30 mL / \min

), caution and close monitoring should occur if orlistat, liraglutide, semaglutide, or tirzepatide is used. Phentermine-topiramate and naltrexone-bupropion should be avoided in patients with severe kidney impairment.

^{7}

30 - 49 mL / \min

). 對於重度腎功能不全的患者（eGFR

< 30 mL / \min

），如果使用奧利司他、利拉魯肽、塞馬魯肽或替卡格雷，應謹慎並密切監測。重度腎功能不全的患者應避免使用芬特明-托吡酯和納曲酮-布普品。

^{7}

^{c S Suggestions applicable to patients with mild to moderate hepatic impairment}

(Child-Pugh score of 5-9). For patients with severe hepatic impairment (Child-Pugh score of >9), antiobesity medications should generally be avoided in the primary care setting.

^{7}

^{c S Suggestions applicable to patients with mild to moderate hepatic impairment}

（Child-Pugh 分數為 5-9）。對於重度肝功能不全的患者（Child-Pugh 分數 >9），在初級護理環境中通常應避免使用抗肥胖藥物。

^{7}

^{d}

Only a small percentage of participants in randomized controlled trials of listed medications were older adults and subgroup analyses with this population have not been published. Therefore, there are limited data within this population. Guidelines recommend that antiobesity medications be used with extra caution in older adults.

^{7}

^{d}

在列出藥物的隨機對照試驗中，只有一小部分參與者是老年人，且針對這一人群的亞組分析尚未發表。因此，該人群內的數據有限。指導方針建議在老年人中使用抗肥胖藥物時要格外謹慎。

^{7}

Phentermine has relatively low potential for abuse (Schedule IV), and signs of phentermine misuse or physical dependence have not been reported.

^{42}

Topiramate augments

γ

-aminobutyrate activity and inhibits a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/ kainite excitatory glutamate receptors

^{6}

; therefore, phenterminetopiramate works through several central mechanisms to reduce appetite and increase satiety. Naltrexone and bupropion reduce appetite and food cravings through different mechanisms that stimulate proopiomelanocortin neurons.

^{6}

苯特明的濫用潛力相對較低（第四類藥物），並且尚未報告苯特明的濫用或身體依賴的跡象。

^{42}

托吡酯增強

γ

-氨基丁酸活性並抑制α-氨基-3-羥基-5-甲基-4-異噁唑丙酸/凱那酸興奮性谷氨酸受體

^{6}

；因此，苯特明-托吡酯通過幾種中樞機制來減少食慾並增加飽腹感。納曲酮和布普洛尼通過不同的機制刺激前腦啡肽神經元來減少食慾和食物渴望。

^{6}

Phentermine 芬特明

Phentermine was approved in the US for short-term use (3 months or fewer) in 1959, and therefore, its long-term use is considered off-label.

^{32, 33, 42}

The EndocrineSociety and AGA guidelines recommend long-term phentermine use to treat obesity in adults without cardiovascular disease.

^{6, 9}

Few RCTs have tested the efficacy and safety of phentermine for more than 3 months

^{45}

and long-term trials are needed for the FDA to consider extending the approved duration of use. One 6 -month RCT reported that phentermine 7.5 mg was associated with

5.5 %

weight loss and phentermine 15 mg was associated with

6.1 %

weight loss, which were significantly greater than

2.3 %

weight loss with placebo.

^{24}

More than

40 %

of participants achieved

5 %

or greater
苯丁胺於 1959 年在美國獲准短期使用（3 個月或更少），因此其長期使用被視為非標籤使用。內分泌學會和 AGA 指導方針建議在沒有心血管疾病的成年人中長期使用苯丁胺來治療肥胖。很少有隨機對照試驗測試苯丁胺超過 3 個月的療效和安全性，並且需要長期試驗以便 FDA 考慮延長批准的使用期限。一項為期 6 個月的隨機對照試驗報告指出，苯丁胺 7.5 毫克與體重減輕相關，苯丁胺 15 毫克與體重減輕相關，這些減輕的體重顯著大於安慰劑的體重減輕。超過參與者達到或超過。
weight loss with either dose of phentermine at 6 months.

^{24}

Another RCT reported that phentermine 15 mg reduced weight by

4.1 %

compared with

0.6 %

for placebo at 6-month follow-up.

^{46}

在 6 個月內，使用任一劑量的苯特明減重。

^{24}

另一項隨機對照試驗報告指出，15 毫克的苯特明在 6 個月的隨訪中相比於安慰劑減少了

4.1 %

的體重。

0.6 %

There is little evidence regarding cardiometabolic outcomes with phentermine. A large observational study reported that phentermine use for more than 3 months was associated with greater weight reduction without increased risk of adverse cardiovascular events at 3 -year follow-up.

^{47}

No elevations in blood pressure were reported with phentermine use for 6 months and SBP decreased with its use (Table 1).

^{24, 46, 47}

關於芬特明對心臟代謝結果的證據很少。一項大型觀察性研究報告指出，使用芬特明超過 3 個月與更大的體重減輕相關，且在 3 年隨訪中未增加不良心血管事件的風險。

^{47}

使用芬特明 6 個月未報告血壓升高，且使用後收縮壓下降（表 1）。

^{24, 46, 47}

Phentermine is the most inexpensive AOM for patients without insurance coverage for AOMs (Table 3). Clinicians should check that local regulations permit long-term prescribing of phentermine (eg, state medical and pharmacy boards) and should counsel patients about the off-label use, limited clinical trial data supporting long-term use, and unknown cardiovascular risks.
芬特明是對於沒有 AOM 保險覆蓋的患者來說最便宜的 AOM（表 3）。臨床醫生應檢查當地法規是否允許長期開處方芬特明（例如，州醫療和藥房委員會），並應向患者諮詢關於非標籤使用、支持長期使用的臨床試驗數據有限以及未知的心血管風險。

Few or no serious adverse events occurred in studies with a duration of 6 months or longer.

^{24, 46, 47}

Common adverse effects are xerostomia (

7 % - 12 %

), insomnia (

6 % - 11 %

), headache (

10 % - 12 %

), and constipation (4%-8%),

^{24, 32, 33, 46}

which may improve with dose reduction (Table 3). Phentermine may be unavailable in some countries outside the US where regulators have concerns about an
在持續 6 個月或更長時間的研究中，幾乎沒有或沒有嚴重的不良事件發生。

^{24, 46, 47}

常見的不良反應包括口乾（

7 % - 12 %

）、失眠（

6 % - 11 %

）、頭痛（

10 % - 12 %

）和便秘（4%-8%），

^{24, 32, 33, 46}

這些情況可能會隨著劑量減少而改善（表 3）。在一些對於藥物安全性有顧慮的美國以外的國家，芬特明可能無法獲得。

Medication, US approved population, and cost $^{a}$
藥物、美國批准的人口和成本 $^{a}$ Administration and titration
管理和滴定 Drug interactions 藥物相互作用 Patient populations with obesity
肥胖患者群體 Strategies to improve safety and tolerability related to common adverse effects
改善與常見不良反應相關的安全性和耐受性的策略

Consider use 考慮使用 Use with caution 小心使用 Avoid use $^{b}$ 避免使用 $^{b}$

Orlistat \({ }^{12}\) \(\geq 12\) y \$675/mo Discounts/coupons available online to reduce to approximately \$200/mo; generic formulations may be available in some countries

口服片劑與含脂肪的餐食一起服用，每天三次（120 毫克）製造商建議的劑量調整：無

Oral tablet taken with fat-containing meals 3 times a day ( 120 mg )

Manufacturerrecommended titration: none

Levothyroxine Warfarin Amiodarone Cyclosporine AEDs Antiretroviral drugs
左甲狀腺素華法林氨碘酮環孢素抗癲癇藥逆轉錄病毒藥物

成人：2 型糖尿病以降低 A

A_{c}

高血壓以降低血壓高脂血症以降低低密度脂蛋白 2 型糖尿病預防體重維持青少年

Adults with:

type 2 diabetes to lower A

A_{c}

HTN to lower BP

HLD to lower LDL

type 2 diabetes

prevention

Weight-loss

maintenance

Adolescents

歷史：頻繁腹瀉草酸鈣腎結石在高脂飲食（例如，低碳水化合物，生酮飲食）後出現的腸胃道副作用增加

History of:

Frequent diarrhea

Oxalate nephrolithiasis

Following a high-fat diet (eg, low-CHO, ketogenic) as increased GI side effects

吸收不良膽汁淤積的歷史

History of:

Malabsorption

Cholestasis

建議：均衡、低熱量飲食，脂肪熱量佔比低於 30%，以減少腸胃不良反應。腸胃不良反應通常在 4 週內減輕。睡前服用含有多種維生素的脂溶性維生素（A、E、D、K、β-胡蘿蔔素），以避免缺乏

Counsel on:

Balanced, low-calorie diet with < 30% of calories from fat to reduce GI adverse effects

GI adverse effects typically subside within 4 weeks

Take MVI-containing fat-soluble vitamins (A, E, D, K, beta-carotene) at bedtime to avoid deficiencies

\begin{aligned} Phentermine^{32, 33} \\ \geq 16 y \\ $ 40 - $ 95 / mo \\ Discounts/coupons \\ available online to \\ reduce to approximately \\ $ 8 / m o; generic \\ formulations may be \\ available in some \\ countries \end{aligned}

每日早上服用口服片或膠囊（

15 mg, 30 mg

，或 37.5 毫克

)^{c}

口服片每日最多服用 3 次

(8 mg)^{c}

製造商建議的劑量調整：無

Oral tablet or capsule taken daily in the morning (

15 mg, 30 mg

, or 37.5 mg

)^{c}

Oral tablet taken up to 3 times a day

(8 mg)^{c}

Manufacturerrecommended titration: none

Alcohol MAOIs 酒精單胺氧化酶抑制劑

成人：最低自付費用無 AOM 保障

Adults with:

No AOM coverage for lowest out-of-pocket costs

失眠的歷史不足的睡眠經常性便秘

History of:

Insomnia

Insufficient sleep

Frequent constipation

CVD 物質使用障礙激動狀態青光眼甲狀腺功能亢進失控高血壓

History of:

CVD

Substance use disorder

Agitated states

Glaucoma

Hyperthyroidism

Uncontrolled HTN

建議：攝取水分和膳食纖維以減少口乾和便秘監測和調整：

H R

和血壓以隨著開始和劑量調整而增加；降低劑量從低劑量開始（每日 8 毫克或 15 毫克）；緩慢調整以平衡體重減輕和不良反應；並非所有患者都需要最大劑量

Counsel on:

Water and dietary fiber intake to reduce dry mouth and constipation

Monitor and adjust:

H R

and BP for increasing with initiation and titration; lower dose

Begin on low dose ( 8 mg or 15 mg daily); titrate slowly to balance weight loss and adverse effects; not all patients need maximum dose

Phentermine- topiramate \({ }^{25}\) \(\geq 12\) y \$250/mo Discounts/coupons available online to reduce to approximately \$100/mo

每日早上服用口服膠囊

^{c}

製造商建議的劑量調整：第 1-2 週：

3.75 / 23 mg

第 3-13 週：

7.5 / 46 mg

第 14 週（3 個月）：如果達到

3 %

體重（成人）或 BMI（青少年）減少：第 14 週及以後：

7.5 / 46 mg

如果未達到

3 %

減少：第 14-15 週：

11.25 / 69 mg

第 16 週及以後：

15 / 92 mg

Oral capsule taken daily in the morning

^{c}

Manufacturerrecommended titration:

Week 1-2:

3.75 / 23 mg

Week 3-13:

7.5 / 46 mg

Week 14 (3 mo):

3 %

reduction

in weight (adult)

or BMI

(adolescent)

met:

Week 14 and beyond:

7.5 / 46 mg

3 %

reduction not achieved:

Week 14-15:

11.25 / 69 mg

Week 16 and beyond:

15 / 92 mg

酒精口服避孕藥阿米替林非鉀保留利尿劑抗癲癇藥碳酸酐酶抑制劑單胺氧化酶抑制劑

Alcohol

OCPs

Amitriptyline

Nonpotassium-

sparing

diuretics

AEDs

Carbonic

anhydrase

inhibitors

MAOIS

成年人：2 型糖尿病以降低

A_{1 c}

高血壓以降低血壓中心肥胖以降低腰圍缺乏 AOM 覆蓋以降低自付費用

Adults with: type 2 diabetes to lower

A_{1 c}

HTN to lower BP Central adiposity to lower WC

Lack AOM coverage as lower out-of-pocket costs

失眠的歷史睡眠不足頻繁便秘腎結石重度憂鬱症需要精神敏銳的職業

History of:

Insomnia

Insufficient sleep

Frequent constipation

Nephrolithiasis

MDD

Occupation requiring mental acuity

狹角型青光眼的歷史甲狀腺功能亢進潛在懷孕的人未使用有效避孕措施作為出生缺陷（口腔裂隙）的風險

History of:

Narrow-angle glaucoma

Hyperthyroidism

People with pregnancy potential who do not use effective contraception as risk of birth defects (oral clefts)

建議：攝取水分和膳食纖維以減少口乾和便秘服用口服避孕藥的患者可能會出現不規則出血；懷孕風險無變化監測和調整：減慢劑量增加可能減少不良反應並提高耐受性如果感覺異常、情緒或認知困難（“腦霧”）影響日常活動，則降低劑量治療前和治療期間檢查電解質以增加肌酐並降低

{HCO}_{3}

；如有需要則降低劑量

Counsel on:

Water and dietary fiber intake to reduce dry mouth and constipation

Irregular bleeding may occur for patients taking OCPs; no change in risk of pregnancy

Monitor and adjust:

Slowing titration may reduce adverse effects and increase tolerability

Lower dose if paresthesia, mood, or cognitive difficulties ("brain fog") impair daily activities

Electrolytes before and during treatment to increase Cr and lower

{HCO}_{3}

; lower dose if needed

Naltrexone-bupropion

^{26}

每月 740 美元在線有折扣/優惠券可減少至約每月 100 美元

Naltrexone-bupropion

^{26}

\geq 18 y

$740/mo

Discounts/coupons available online to reduce to approximately $100/mo

口服片每日最多服用兩次（

8 / 90 mg

）製造商建議的劑量調整：第 1 週：每日 1 片第 2 週：每日 2 次，每次 1 片第 3 週：每天早上 2 片，晚上 1 片第 4 週及以後：每日 2 次，每次 2 片

Oral tablet taken up to twice a day (

8 / 90 mg

)

Manufacturerrecommended titration:

Week 1: 1 tablet daily

Week 2: 1 tablet twice a day

Week 3: 2 tablets every morning and 1 tablet every evening

Week 4 and beyond: 2 tablets twice a day

鴉片類藥物 SSRIs 或 TCAs 抗精神病藥物

β

-阻滯劑 1C 類抗心律不整藥物地高辛氯吡格雷或氯吡格雷左旋多巴或阿曼他丁 AEDs 抗逆轉錄病毒藥物 MAOIS

Opioids

SSRIs or TCAs

Antipsychotics

β

-Blockers

Type 1C

antiar-

rhythmics

Digoxin

Ticlopidine or clopidogrel

Levodopa or amantadine

AEDs

Antiretroviral drugs

MAOIS

成年人：2 型糖尿病以降低

A_{1 c}

中央脂肪堆積以降低腰圍缺乏 AOM 覆蓋以降低自付費用和折扣

Adults with:

Type 2 diabetes to lower

A_{1 c}

Central adiposity to lower WC

Lack AOM coverage as lower out-of-pocket costs with discounts

MDD SMI 肝病的歷史在高脂飲食（例如，低碳水化合物、酮飲食）下作為增加的不良影響

History of:

MDD

SMI

Liver disease

Following a high-fat diet (eg, low-CHO, ketogenic) as increased adverse effects

物質使用障礙狹角型青光眼癲癇障礙食慾不振或暴食症無法控制的高血壓慢性鴉片類藥物使用

History of:

Substance use disorder

Narrow-angle glaucoma

Seizure disorder

Anorexia or bulimia

Uncontrolled HTN

Chronic opioid use

建議：在睡前服用晚間劑量

\geq 3 h

以減少睡眠干擾；攝取水分和膳食纖維以減少口乾和便秘；減少食物份量以控制噁心；與鴉片類藥物的相互作用；如果需要短期鴉片類藥物，提供藥物管理策略；監測和調整：減慢劑量增加可能減少不良反應並提高耐受性；並非所有患者都需要最大劑量；心率和血壓在開始和劑量增加時上升；降低劑量；頭痛；降低劑量；情緒和自殺意念；降低劑量或在有自殺意念時停用

Counsel on:

Administering evening dose

\geq 3 h

before bedtime to reduce sleep disturbance

Water and dietary fiber intake to reduce dry mouth and constipation

Lower portion size to manage nausea

Interaction with opioids; provide medication management strategy if short-term opioids needed

Monitor and adjust:

Slowing titration may reduce adverse effects and increase tolerability; not all patients need maximum dose

HR and BP increased with initiation and titration; lower dose

Headache; lower dose

Mood and SI; lower dose or discontinue with SI

Medication, US approved population, and cost ^("a ") Administration and titration Drug interactions Patient populations with obesity Strategies to improve safety and tolerability related to common adverse effects Consider use Use with caution Avoid use ^("b ") Orlistat ${ }^{12}$ $\geq 12$ y \$675/mo Discounts/coupons available online to reduce to approximately \$200/mo; generic formulations may be available in some countries "Oral tablet taken with fat-containing meals 3 times a day ( 120 mg ) Manufacturerrecommended titration: none" Levothyroxine Warfarin Amiodarone Cyclosporine AEDs Antiretroviral drugs "Adults with: type 2 diabetes to lower A A_(c) HTN to lower BP HLD to lower LDL type 2 diabetes prevention Weight-loss maintenance Adolescents" "History of: Frequent diarrhea Oxalate nephrolithiasis Following a high-fat diet (eg, low-CHO, ketogenic) as increased GI side effects" "History of: Malabsorption Cholestasis" "Counsel on: Balanced, low-calorie diet with < 30% of calories from fat to reduce GI adverse effects GI adverse effects typically subside within 4 weeks Take MVI-containing fat-soluble vitamins (A, E, D, K, beta-carotene) at bedtime to avoid deficiencies" " Phentermine ^(32,33) >= 16 y $40 - $95// mo Discounts/coupons available online to reduce to approximately $8//mo; generic formulations may be available in some countries " "Oral tablet or capsule taken daily in the morning ( 15mg,30mg, or 37.5 mg)^("c ") Oral tablet taken up to 3 times a day (8mg)^("c ") Manufacturerrecommended titration: none" Alcohol MAOIs "Adults with: No AOM coverage for lowest out-of-pocket costs" "History of: Insomnia Insufficient sleep Frequent constipation" "History of: CVD Substance use disorder Agitated states Glaucoma Hyperthyroidism Uncontrolled HTN" "Counsel on: Water and dietary fiber intake to reduce dry mouth and constipation Monitor and adjust: HR and BP for increasing with initiation and titration; lower dose Begin on low dose ( 8 mg or 15 mg daily); titrate slowly to balance weight loss and adverse effects; not all patients need maximum dose" Phentermine- topiramate ${ }^{25}$ $\geq 12$ y \$250/mo Discounts/coupons available online to reduce to approximately \$100/mo "Oral capsule taken daily in the morning ^("c ") Manufacturerrecommended titration: Week 1-2: 3.75//23mg Week 3-13: 7.5//46mg Week 14 (3 mo): if 3% reduction in weight (adult) or BMI (adolescent) met: Week 14 and beyond: 7.5//46mg If 3% reduction not achieved: Week 14-15: 11.25//69mg Week 16 and beyond: 15//92mg" "Alcohol OCPs Amitriptyline Nonpotassium- sparing diuretics AEDs Carbonic anhydrase inhibitors MAOIS" "Adults with: type 2 diabetes to lower A_(1c) HTN to lower BP Central adiposity to lower WC Lack AOM coverage as lower out-of-pocket costs" "History of: Insomnia Insufficient sleep Frequent constipation Nephrolithiasis MDD Occupation requiring mental acuity" "History of: Narrow-angle glaucoma Hyperthyroidism People with pregnancy potential who do not use effective contraception as risk of birth defects (oral clefts)" "Counsel on: Water and dietary fiber intake to reduce dry mouth and constipation Irregular bleeding may occur for patients taking OCPs; no change in risk of pregnancy Monitor and adjust: Slowing titration may reduce adverse effects and increase tolerability Lower dose if paresthesia, mood, or cognitive difficulties ("brain fog") impair daily activities Electrolytes before and during treatment to increase Cr and lower HCO_(3); lower dose if needed" "Naltrexone-bupropion ^(26) >= 18y $740/mo Discounts/coupons available online to reduce to approximately $100/mo" "Oral tablet taken up to twice a day ( 8//90mg ) Manufacturerrecommended titration: Week 1: 1 tablet daily Week 2: 1 tablet twice a day Week 3: 2 tablets every morning and 1 tablet every evening Week 4 and beyond: 2 tablets twice a day" "Opioids SSRIs or TCAs Antipsychotics beta-Blockers Type 1C antiar- rhythmics Digoxin Ticlopidine or clopidogrel Levodopa or amantadine AEDs Antiretroviral drugs MAOIS" "Adults with: Type 2 diabetes to lower A_(1c) Central adiposity to lower WC Lack AOM coverage as lower out-of-pocket costs with discounts" "History of: MDD SMI Liver disease Following a high-fat diet (eg, low-CHO, ketogenic) as increased adverse effects" "History of: Substance use disorder Narrow-angle glaucoma Seizure disorder Anorexia or bulimia Uncontrolled HTN Chronic opioid use" "Counsel on: Administering evening dose >= 3h before bedtime to reduce sleep disturbance Water and dietary fiber intake to reduce dry mouth and constipation Lower portion size to manage nausea Interaction with opioids; provide medication management strategy if short-term opioids needed Monitor and adjust: Slowing titration may reduce adverse effects and increase tolerability; not all patients need maximum dose HR and BP increased with initiation and titration; lower dose Headache; lower dose Mood and SI; lower dose or discontinue with SI"

| Medication, US approved population, and cost ${ }^{\text {a }}$ | Administration and titration | Drug interactions | Patient populations with obesity | | | Strategies to improve safety and tolerability related to common adverse effects | | :---: | :---: | :---: | :---: | :---: | :---: | :---: | | | | | Consider use | Use with caution | Avoid use ${ }^{\text {b }}$ | | | ```Orlistat ${ }^{12}$ $\geq 12$ y \$675/mo Discounts/coupons available online to reduce to approximately \$200/mo; generic formulations may be available in some countries``` | Oral tablet taken with fat-containing meals 3 times a day ( 120 mg ) Manufacturerrecommended titration: none | Levothyroxine Warfarin Amiodarone Cyclosporine AEDs Antiretroviral drugs | Adults with: type 2 diabetes to lower A $\mathrm{A}_{\mathrm{c}}$ HTN to lower BP HLD to lower LDL type 2 diabetes prevention Weight-loss maintenance Adolescents | History of: Frequent diarrhea Oxalate nephrolithiasis Following a high-fat diet (eg, low-CHO, ketogenic) as increased GI side effects | History of: Malabsorption Cholestasis | Counsel on: Balanced, low-calorie diet with < 30% of calories from fat to reduce GI adverse effects GI adverse effects typically subside within 4 weeks Take MVI-containing fat-soluble vitamins (A, E, D, K, beta-carotene) at bedtime to avoid deficiencies | | $\begin{aligned} & \text { Phentermine }{ }^{32,33} \\ & \geq 16 \text { y } \\ & \$ 40 \text { - } \$ 95 / \text { mo } \\ & \text { Discounts/coupons } \\ & \text { available online to } \\ & \text { reduce to approximately } \\ & \$ 8 / m o ; \text { generic } \\ & \text { formulations may be } \\ & \text { available in some } \\ & \text { countries } \end{aligned}$ | Oral tablet or capsule taken daily in the morning ( $15 \mathrm{mg}, 30 \mathrm{mg}$, or 37.5 mg$)^{\text {c }}$ Oral tablet taken up to 3 times a day $(8 \mathrm{mg})^{\text {c }}$ Manufacturerrecommended titration: none | Alcohol MAOIs | Adults with: No AOM coverage for lowest out-of-pocket costs | History of: Insomnia Insufficient sleep Frequent constipation | History of: CVD Substance use disorder Agitated states Glaucoma Hyperthyroidism Uncontrolled HTN | Counsel on: Water and dietary fiber intake to reduce dry mouth and constipation Monitor and adjust: $H R$ and BP for increasing with initiation and titration; lower dose Begin on low dose ( 8 mg or 15 mg daily); titrate slowly to balance weight loss and adverse effects; not all patients need maximum dose | | ```Phentermine- topiramate ${ }^{25}$ $\geq 12$ y \$250/mo Discounts/coupons available online to reduce to approximately \$100/mo``` | Oral capsule taken daily in the morning ${ }^{\text {c }}$ Manufacturerrecommended titration: Week 1-2: $3.75 / 23 \mathrm{mg}$ Week 3-13: $7.5 / 46 \mathrm{mg}$ Week 14 (3 mo): if $3 \%$ reduction in weight (adult) or BMI (adolescent) met: Week 14 and beyond: $7.5 / 46 \mathrm{mg}$ If $3 \%$ reduction not achieved: Week 14-15: $11.25 / 69 \mathrm{mg}$ Week 16 and beyond: $15 / 92 \mathrm{mg}$ | Alcohol OCPs Amitriptyline Nonpotassium- sparing diuretics AEDs Carbonic anhydrase inhibitors MAOIS | Adults with: type 2 diabetes to lower $\mathrm{A}_{1 \mathrm{c}}$ HTN to lower BP Central adiposity to lower WC Lack AOM coverage as lower out-of-pocket costs | History of: Insomnia Insufficient sleep Frequent constipation Nephrolithiasis MDD Occupation requiring mental acuity | History of: Narrow-angle glaucoma Hyperthyroidism People with pregnancy potential who do not use effective contraception as risk of birth defects (oral clefts) | Counsel on: Water and dietary fiber intake to reduce dry mouth and constipation Irregular bleeding may occur for patients taking OCPs; no change in risk of pregnancy Monitor and adjust: Slowing titration may reduce adverse effects and increase tolerability Lower dose if paresthesia, mood, or cognitive difficulties ("brain fog") impair daily activities Electrolytes before and during treatment to increase Cr and lower $\mathrm{HCO}_{3}$; lower dose if needed | | Naltrexone-bupropion ${ }^{26}$ $\geq 18 \mathrm{y}$ $740/mo Discounts/coupons available online to reduce to approximately $100/mo | Oral tablet taken up to twice a day ( $8 / 90 \mathrm{mg}$ ) Manufacturerrecommended titration: Week 1: 1 tablet daily Week 2: 1 tablet twice a day Week 3: 2 tablets every morning and 1 tablet every evening Week 4 and beyond: 2 tablets twice a day | Opioids SSRIs or TCAs Antipsychotics $\beta$-Blockers Type 1C antiar- rhythmics Digoxin Ticlopidine or clopidogrel Levodopa or amantadine AEDs Antiretroviral drugs MAOIS | Adults with: Type 2 diabetes to lower $\mathrm{A}_{1 \mathrm{c}}$ Central adiposity to lower WC Lack AOM coverage as lower out-of-pocket costs with discounts | History of: MDD SMI Liver disease Following a high-fat diet (eg, low-CHO, ketogenic) as increased adverse effects | History of: Substance use disorder Narrow-angle glaucoma Seizure disorder Anorexia or bulimia Uncontrolled HTN Chronic opioid use | Counsel on: Administering evening dose $\geq 3 \mathrm{~h}$ before bedtime to reduce sleep disturbance Water and dietary fiber intake to reduce dry mouth and constipation Lower portion size to manage nausea Interaction with opioids; provide medication management strategy if short-term opioids needed Monitor and adjust: Slowing titration may reduce adverse effects and increase tolerability; not all patients need maximum dose HR and BP increased with initiation and titration; lower dose Headache; lower dose Mood and SI; lower dose or discontinue with SI |

Consider use 考慮使用 Use with caution 小心使用 Avoid use $^{b}$ 避免使用 $^{b}$

Liraglutide }\mp@subsup{}{}{27 212 y $1600/mo
Discounts/coupons  折扣/優惠券
available online to  可在線獲得
reduce to approximately  約減至
$1300/mo  $1300/月

Subcutaneous injection administered daily with multidose pen
每日使用多劑量筆進行皮下注射

GLP-1 receptor agonists Insulin Sulfonylureas Meglitinides
GLP-1 受體激動劑胰島素磺酰脲類溴苯脲類

成人：2 型糖尿病以降低

A_{1 c}

高血壓以降低血壓中心肥胖以降低腰圍青少年

Adults with:

Type 2 diabetes to lower

A_{1 c}

HTN to lower BP

Central adiposity to lower WC

Adolescents

病史：頻繁噁心頻繁便秘頻繁腹瀉膽結石胰腺炎

History of:

Frequent nausea

Frequent constipation

Frequent diarrhea

Cholelithiasis

Pancreatitis

嚴重胃腸疾病的歷史

History of:

Severe gastrointestinal disease

建議：輪換注射部位以減少疼痛；可使用大腿、上臂或腹部

Counsel on:

Rotating injection site location to reduce pain; may use thigh, upper arm, or abdomen

Manufacturerrecommended titration:
製造商建議的滴定： Suicide attempts $^{d}$ 自殺嘗試 $^{d}$ Water and dietary fiber intake to reduce constipation
攝取水分和膳食纖維以減少便秘

Personal or family history of medullary thyroid carcinoma
甲狀腺髓樣癌的個人或家族病史 Lower portion size to manage nausea
減少份量以控制噁心

第 1 週：0.6 毫克第 2 週：1.2 毫克第 3 週：1.8 毫克第 4 週：2.4 毫克

Week 1: 0.6 mg

Week 2: 1.2 mg

Week 3: 1.8 mg

Week 4: 2.4 mg

Last meal

\geq 2 h

before bedtime to reduce heartburn
睡前最後一餐

\geq 2 h

以減少胃灼熱

Refrigerate multi-dose pens (may be kept at room temperature for 30 d )
冷藏多劑量筆（可在室溫下保存 30 天）

Monitor and adjust: 監控和調整：

Week 5 and beyond: 3.0 mg
第 5 週及以後：3.0 毫克 Slowing titration may reduce side effects and increase tolerability; not all patients need maximum dose
減緩滴定可能減少副作用並增加耐受性；並非所有患者都需要最大劑量

Of note, prescription for pen needles must be provided (dispensed medication does not include needles for administration)
值得注意的是，處方必須提供針頭（配藥不包括用於給藥的針頭）

所有患者需要最大劑量。使用胰島素或磺脲類藥物的患者可能會出現低血糖；考慮在開始使用利拉魯肽時降低這些藥物的劑量以降低風險

all patients need maximum dose

Hypoglycemia in patients on insulin or sulfonylureas; consider lowering doses of these medications with liraglutide initiation to reduce risk

HR increase, particularly among patients with CVD; lower dose or discontinue if needed
HR 增加，特別是在心血管疾病患者中；如有需要，降低劑量或停止使用

Mood and SI

^{d}

; lower dose or discontinue with SI
情緒和自殺意念

^{d}

; 降低劑量或停止使用自殺意念

\begin{aligned} Semaglutide^{28} \\ \geq 12 y \\ $ 1600 / mo \\ Discounts/coupons \\ available online to \\ reduce to approximately \\ $ 1100 / mo \end{aligned}

Subcutaneous injection administered weekly with single-dose pen
每週使用單劑量筆進行皮下注射

GLP-1 受體激動劑胰島素磺酰脲類溴苯脲類

GLP-1

receptor

agonists

Insulin

Sulfonylureas

Meglitinides

成人患有：2 型糖尿病以降低 A

_{1 c}

高血壓以降低血壓中心肥胖以降低腰圍心血管疾病以降低重大不良心臟事件 HFpEF 以降低心衰症狀

Adults with:

Type 2 diabetes to lower A

_{1 c}

HTN to lower BP

Central adiposity to lower WC

CVD to lower major adverse cardiac events

HFpEF to lower heart failure symptoms

病史：頻繁噁心頻繁便秘頻繁腹瀉膽結石胰腺炎糖尿病相關眼病

History of:

Frequent nausea

Frequent constipation

Frequent diarrhea

Cholelithiasis

Pancreatitis

Diabetes-related eye disease

嚴重胃腸疾病的歷史

History of:

Severe gastrointestinal disease

建議：輪換注射部位以減少疼痛；可使用大腿、上臂或腹部

Counsel on:

Rotating injection site location to reduce pain; may use thigh, upper arm, or abdomen

Personal or family history of medullary thyroid carcinoma
甲狀腺髓樣癌的個人或家族病史 Lower dietary fat and portion size to manage nausea
降低飲食中的脂肪和份量以管理噁心

Week 1-4: 0.25 mg
第 1-4 週：0.25 毫克 Last meal $\geq 2 h$ before bedtime to reduce heartburn
睡前最後一餐 $\geq 2 h$ 以減少胃灼熱

第 5-8 週：0.5 毫克

Week 5-8:

0.5 mg

Take MVI daily to avoid micronutrient deficiencies
每天服用 MVI 以避免微量營養素缺乏

Week 9-12: 1.0 mg
第 9-12 週：1.0 毫克 Refrigerate single-dose pens (may be kept at room temperature for 28 d)
將單劑量筆冷藏（可在室溫下保存 28 天）

$\begin{aligned} Week 13-16: \\ 1.7 mg \end{aligned}$ Monitor and adjust: 監控和調整：

Week 17 and beyond: 2.4 mg Of note, 1.7 mg may be a maintenance dose for adults
第 17 週及以後：2.4 毫克值得注意的是，1.7 毫克可能是成人的維持劑量 Slowing titration may reduce adverse effects and increase tolerability; not all patients need to reach maintenance dose(s)
減緩滴定可能減少不良反應並增加耐受性；並非所有患者都需要達到維持劑量

Hypoglycemia in patients on insulin or sulfonylureas; consider lowering doses of these medications with semaglutide initiation to reduce risk
使用胰島素或磺脲類藥物的患者低血糖；考慮在開始使用塞馬魯肽時降低這些藥物的劑量以降低風險

HR increase, particularly among patients with known CVD; lower dose or discontinue if needed
HR 增加，特別是在已知心血管疾病的患者中；如有需要，降低劑量或停止使用

Mood and SI

^{d}

; lower dose or discontinue with SI
情緒和自殺意念

^{d}

; 降低劑量或停止使用自殺意念

Medication, US approved population, and cost ^("a ") Administration and titration Drug interactions Patient populations with obesity Strategies to improve safety and tolerability related to common adverse effects Consider use Use with caution Avoid use ^("b ") Liraglutide }\mp@subsup{}{}{27 212 y $1600/moDiscounts/couponsavailable online toreduce to approximately$1300/mo Subcutaneous injection administered daily with multidose pen GLP-1 receptor agonists Insulin Sulfonylureas Meglitinides "Adults with: Type 2 diabetes to lower A_(1c) HTN to lower BP Central adiposity to lower WC Adolescents" "History of: Frequent nausea Frequent constipation Frequent diarrhea Cholelithiasis Pancreatitis" "History of: Severe gastrointestinal disease" "Counsel on: Rotating injection site location to reduce pain; may use thigh, upper arm, or abdomen" Manufacturerrecommended titration: Suicide attempts ^("d ") Water and dietary fiber intake to reduce constipation Personal or family history of medullary thyroid carcinoma Lower portion size to manage nausea "Week 1: 0.6 mg Week 2: 1.2 mg Week 3: 1.8 mg Week 4: 2.4 mg" Last meal >= 2h before bedtime to reduce heartburn Refrigerate multi-dose pens (may be kept at room temperature for 30 d ) Monitor and adjust: Week 5 and beyond: 3.0 mg Slowing titration may reduce side effects and increase tolerability; not all patients need maximum dose Of note, prescription for pen needles must be provided (dispensed medication does not include needles for administration) "all patients need maximum dose Hypoglycemia in patients on insulin or sulfonylureas; consider lowering doses of these medications with liraglutide initiation to reduce risk" HR increase, particularly among patients with CVD; lower dose or discontinue if needed Mood and SI ^("d "); lower dose or discontinue with SI " Semaglutide ^(28) >= 12y $1600//mo Discounts/coupons available online to reduce to approximately $1100//mo" Subcutaneous injection administered weekly with single-dose pen "GLP-1 receptor agonists Insulin Sulfonylureas Meglitinides" "Adults with: Type 2 diabetes to lower A _(1c) HTN to lower BP Central adiposity to lower WC CVD to lower major adverse cardiac events HFpEF to lower heart failure symptoms" "History of: Frequent nausea Frequent constipation Frequent diarrhea Cholelithiasis Pancreatitis Diabetes-related eye disease" "History of: Severe gastrointestinal disease" "Counsel on: Rotating injection site location to reduce pain; may use thigh, upper arm, or abdomen" Manufacturerrecommended titration: Suicide attempts ^("d ") Water and dietary fiber intake to reduce constipation Personal or family history of medullary thyroid carcinoma Lower dietary fat and portion size to manage nausea Week 1-4: 0.25 mg Last meal >= 2h before bedtime to reduce heartburn "Week 5-8: 0.5 mg" Take MVI daily to avoid micronutrient deficiencies Week 9-12: 1.0 mg Refrigerate single-dose pens (may be kept at room temperature for 28 d) " Week 13-16: 1.7mg" Monitor and adjust: Week 17 and beyond: 2.4 mg Of note, 1.7 mg may be a maintenance dose for adults Slowing titration may reduce adverse effects and increase tolerability; not all patients need to reach maintenance dose(s) Hypoglycemia in patients on insulin or sulfonylureas; consider lowering doses of these medications with semaglutide initiation to reduce risk HR increase, particularly among patients with known CVD; lower dose or discontinue if needed Mood and SI ^("d "); lower dose or discontinue with SI

| Medication, US approved population, and cost ${ }^{\text {a }}$ | Administration and titration | Drug interactions | Patient populations with obesity | | | Strategies to improve safety and tolerability related to common adverse effects | | :---: | :---: | :---: | :---: | :---: | :---: | :---: | | | | | Consider use | Use with caution | Avoid use ${ }^{\text {b }}$ | | | ```Liraglutide }\mp@subsup{}{}{27 212 y $1600/mo```Discounts/couponsavailable online toreduce to approximately$1300/mo | Subcutaneous injection administered daily with multidose pen | GLP-1 receptor agonists Insulin Sulfonylureas Meglitinides | Adults with: Type 2 diabetes to lower $\mathrm{A}_{1 \mathrm{c}}$ HTN to lower BP Central adiposity to lower WC Adolescents | History of: Frequent nausea Frequent constipation Frequent diarrhea Cholelithiasis Pancreatitis | History of: Severe gastrointestinal disease | Counsel on: Rotating injection site location to reduce pain; may use thigh, upper arm, or abdomen | | | | | | | | | | | Manufacturerrecommended titration: | | | | Suicide attempts ${ }^{\text {d }}$ | Water and dietary fiber intake to reduce constipation | | | | | | | Personal or family history of medullary thyroid carcinoma | Lower portion size to manage nausea | | | Week 1: 0.6 mg Week 2: 1.2 mg Week 3: 1.8 mg Week 4: 2.4 mg | | | | | Last meal $\geq 2 \mathrm{~h}$ before bedtime to reduce heartburn | | | | | | | | Refrigerate multi-dose pens (may be kept at room temperature for 30 d ) | | | | | | | | Monitor and adjust: | | | Week 5 and beyond: 3.0 mg | | | | | Slowing titration may reduce side effects and increase tolerability; not all patients need maximum dose | | | Of note, prescription for pen needles must be provided (dispensed medication does not include needles for administration) | | | | | all patients need maximum dose Hypoglycemia in patients on insulin or sulfonylureas; consider lowering doses of these medications with liraglutide initiation to reduce risk | | | | | | | | HR increase, particularly among patients with CVD; lower dose or discontinue if needed | | | | | | | | Mood and SI ${ }^{\text {d }}$; lower dose or discontinue with SI | | $\begin{aligned} & \text { Semaglutide }{ }^{28} \\ & \geq 12 \mathrm{y} \\ & \$ 1600 / \mathrm{mo} \\ & \text { Discounts/coupons } \\ & \text { available online to } \\ & \text { reduce to approximately } \\ & \$ 1100 / \mathrm{mo} \end{aligned}$ | Subcutaneous injection administered weekly with single-dose pen | GLP-1 receptor agonists Insulin Sulfonylureas Meglitinides | Adults with: Type 2 diabetes to lower A ${ }_{1 c}$ HTN to lower BP Central adiposity to lower WC CVD to lower major adverse cardiac events HFpEF to lower heart failure symptoms | History of: Frequent nausea Frequent constipation Frequent diarrhea Cholelithiasis Pancreatitis Diabetes-related eye disease | History of: Severe gastrointestinal disease | Counsel on: Rotating injection site location to reduce pain; may use thigh, upper arm, or abdomen | | | | | | | | | | | Manufacturerrecommended titration: | | | | Suicide attempts ${ }^{\text {d }}$ | Water and dietary fiber intake to reduce constipation | | | | | | | Personal or family history of medullary thyroid carcinoma | Lower dietary fat and portion size to manage nausea | | | Week 1-4: 0.25 mg | | | | | Last meal $\geq 2 \mathrm{~h}$ before bedtime to reduce heartburn | | | Week 5-8: 0.5 mg | | | | | Take MVI daily to avoid micronutrient deficiencies | | | Week 9-12: 1.0 mg | | | | | Refrigerate single-dose pens (may be kept at room temperature for 28 d) | | | $\begin{aligned} & \text { Week 13-16: } \\ & 1.7 \mathrm{mg} \end{aligned}$ | | | | | Monitor and adjust: | | | Week 17 and beyond: 2.4 mg Of note, 1.7 mg may be a maintenance dose for adults | | | | | Slowing titration may reduce adverse effects and increase tolerability; not all patients need to reach maintenance dose(s) | | | | | | | | | | | | | | | | Hypoglycemia in patients on insulin or sulfonylureas; consider lowering doses of these medications with semaglutide initiation to reduce risk | | | | | | | | HR increase, particularly among patients with known CVD; lower dose or discontinue if needed | | | | | | | | Mood and SI ${ }^{\text {d }}$; lower dose or discontinue with SI |

unfavorable risk-benefit profile, particularly given the lack of longterm cardiovascular outcomes.

^{42, 48}

不利的風險收益比，特別是考慮到缺乏長期心血管結果。

^{42, 48}

Phentermine-Topiramate 芬特明-托吡酯

Phentermine-topiramate has been approved for long-term use in the US for adults since 2012 and was approved for adolescents (aged

\geq 12

years) in 2022.

^{25}

A meta-analysis of 5 RCTs that included 3407 participants reported that phentermine-topiramate was associated with

8.0 %

greater weight loss than placebo (

95 % Cl, 6.7 % - 9.3 %

) among adults with obesity.

^{15}

At 12 months, mean weight loss was

7.8 %

with phentermine-topiramate

7.5 / 46 mg

and

9.8 %

with phenterminetopiramate

15 / 92 mg .^{49}

A follow-up study reported that these weight
苯丁胺-托吡酯自 2012 年起在美國獲准用於成人的長期使用，並於 2022 年獲准用於青少年（年齡

\geq 12

歲）。

^{25}

一項包含 3407 名參與者的 5 項隨機對照試驗的綜合分析報告顯示，苯丁胺-托吡酯與安慰劑相比，在肥胖成人中與

8.0 %

更大的體重減輕相關（

95 % Cl, 6.7 % - 9.3 %

）。

^{15}

在 12 個月時，使用苯丁胺-托吡酯的平均體重減輕為

7.8 %

，而使用苯丁胺-托吡酯的平均體重減輕為

7.5 / 46 mg

和

9.8 %

。一項後續研究報告顯示這些體重
reductions persisted at 2 years with continued medication use.

^{50}

More than two-thirds of phentermine-topiramate

15 / 92

mg users achieved

5 %

or greater weight loss (Figure 2).

^{17}

Adolescents had a significant

10.4 %

reduction in BMI with phentermine-topiramate

15 / 92 mg

compared with placebo. The safety profile was similar to the safety profile in adults (eTable 2 in the Supplement).

^{51}

減少在持續用藥的情況下持續了兩年。

^{50}

超過三分之二的苯丁胺-托吡酯

15 / 92

毫克使用者達到了

5 %

或更大的體重減輕（圖 2）。

^{17}

青少年在使用苯丁胺-托吡酯

15 / 92 mg

時與安慰劑相比，BMI 顯著減少。安全性概況與成人的安全性概況相似（補充資料中的 eTable 2）。

^{51}

Phentermine-topiramate reduced waist circumference by approximately 11 cm , decreased SBP by approximately 3 mm Hg , and reduced LDL-C by approximately

6 %

among adults with obesity (Table 1).

^{17}

Among 1030 patients with hypertension, phenterminetopiramate

15 / 92 mg

statistically significantly reduced SBP 4.2 mm Hg (

95 % Cl, 2.55 - 5.85

) more than placebo.

^{30}

At 2-year follow-up,
芬特明-托吡酯使肥胖成人的腰圍減少約 11 厘米，收縮壓(SBP)減少約 3 毫米汞柱，低密度脂蛋白膽固醇(LDL-C)減少約

6 %

（見表 1）。在 1030 名高血壓患者中，芬特明-托吡酯

15 / 92 mg

在統計上顯著減少了收縮壓 4.2 毫米汞柱（

95 % Cl, 2.55 - 5.85

）比安慰劑更有效。

^{30}

在 2 年隨訪中，

Medication, US approved population, and cost

^{a}

藥物、美國批准的人口和成本

^{a}

Administration and titration
管理和滴定

Drug interactions 藥物相互作用

Patient populations with obesity
肥胖患者群體

Strategies to improve safety and tolerability related to common adverse effects
改善與常見不良反應相關的安全性和耐受性的策略

Consider use 考慮使用

Use with caution 小心使用

Avoid use

^{b}

避免使用

^{b}

Tirzepatide

^{29}

\geq 18 y

$ 1275 / mo

Discounts/coupons  折扣/優惠券
available online to  可在線獲得
reduce to approximately  約減至

$ 700 / mo

Subcutaneous injection administered weekly with single-dose pen
每週使用單劑量筆進行皮下注射

GLP-1 receptor agonists Insulin Sulfonylureas Meglitinides
GLP-1 受體激動劑胰島素磺酰脲類溴苯脲類

成人患有：2 型糖尿病以降低 A

_{1 c}

高血壓以降低血壓高脂血症以降低低密度脂蛋白中心肥胖以降低腰圍

Adults with:

Type 2 diabetes to lower A

_{1 c}

HTN to lower BP HLD to lower LDL Central adiposity to lower WC

病史：頻繁噁心頻繁便秘頻繁腹瀉膽結石胰腺炎糖尿病相關眼病

History of:

Frequent nausea

Frequent constipation

Frequent diarrhea

Cholelithiasis

Pancreatitis

Diabetes-related eye disease

嚴重胃腸疾病的歷史

History of:

Severe gastrointestinal disease

建議：輪換注射部位以減少疼痛；可使用大腿、上臂或腹部

Counsel on:

Rotating injection site location to reduce pain; may use thigh, upper arm, or abdomen

Manufacturerrecommended titration:
製造商建議的滴定：

Suicide attempts

^{d}

自殺嘗試

^{d}

Water and dietary fiber intake to reduce constipation
攝取水分和膳食纖維以減少便秘

Personal or family history of medullary thyroid carcinoma
甲狀腺髓樣癌的個人或家族病史

Lower dietary fat and portion size to manage nausea
降低飲食中的脂肪和份量以管理噁心

Week 1-4: 2.5 mg
第 1-4 週：2.5 毫克

Last meal

\geq 2 h

before bedtime to reduce heartburn
睡前最後一餐

\geq 2 h

以減少胃灼熱

Week 5-8: 5.0 mg
第 5-8 週：5.0 毫克

Take MVI daily to avoid micronutrient deficiencies
每天服用 MVI 以避免微量營養素缺乏

\begin{aligned} Week 9-12: \\ 7.5 mg \end{aligned}

Refrigerate single-dose pens (may be kept at room temperature for 21 d )
將單劑量筆冷藏（可在室溫下保存 21 天）

Week 13-16: 10.0 mg
第 13-16 週：10.0 毫克

Monitor and adjust: 監控和調整：

第 17-20 週：12.5 毫克

Week 17-20:

12.5 mg

Slowing titration may reduce adverse effects and increase tolerability; 3 different maintenance doses available
減緩滴定可能減少不良反應並增加耐受性；有三種不同的維持劑量可供選擇

Week 21 and beyond: 15.0 mg
第 21 週及以後：15.0 毫克

Hypoglycemia in patients on insulin or sulfonylureas; consider lowering doses of these medications with tirzepatide initiation to reduce risk
使用胰島素或磺脲類藥物的患者低血糖；考慮在開始使用提拉帕肽時降低這些藥物的劑量以降低風險

Of note, 5 mg , 10 mg , or 15 mg may be a maintenance dose for adults
值得注意的是，5 毫克、10 毫克或 15 毫克可能是成人的維持劑量

Mood and SI

^{d}

; lower dose or discontinue with SI
情緒和自殺意念

^{d}

; 降低劑量或停止使用自殺意念

Abbreviations: AED, antiepileptic drugs; AOM, antiobesity medication; BP, blood pressure; CHO, carbohydrate; Cr, creatinine; CVD, cardiovascular disease; GI , gastrointestinal;

{HCO}_{3}

, bicarbonate; HFpEF , heart failure with preserved ejection fraction; HLD, hyperlipidemia; HR, heart rate;
縮寫：AED，抗癲癇藥物；AOM，抗肥胖藥物；BP，血壓；CHO，碳水化合物；Cr，肌酐；CVD，心血管疾病；GI，胃腸道；

{HCO}_{3}

，碳酸氫鹽；HFpEF，保留射血分數的心臟衰竭；HLD，高脂血症；HR，心率；
HTN, hypertension; LDL, low-density lipoprotein; MAOI, monoamine oxidase inhibitor; MDD, major depressive disorder; MVI, multivitamin; OCP, oral contraceptives; SI, suicidal ideation; SMI, serious mental illness; WC, waist circumference.
HTN，高血壓；LDL，低密度脂蛋白；MAOI，單胺氧化酶抑制劑；MDD，重度抑鬱症；MVI，綜合維生素；OCP，口服避孕藥；SI，自殺意念；SMI，嚴重精神疾病；WC，腰圍。

^{a}

Given that many patients lack insurance coverage for AOMs, costs provided reflect US retail prices identified in early March 2024 on GoodRx.com. Below the retail price, an estimated price is provided if online discounts or coupons are used that are available online through pharmaceutical manufacturers or websites like GoodRx. Discounts from pharmaceutical manufacturers have certain eligibility criteria and are not available to all patients (eg, Medicare beneficiaries are ineligible). Patients with insurance coverage for a medication may have lower out-of-pocket costs than those listed in this table.

^{a}

鑑於許多患者缺乏急性中耳炎藥物的保險覆蓋，所提供的成本反映了 2024 年 3 月初在 GoodRx.com 上識別的美國零售價格。在零售價格下方，提供了一個估計價格，如果使用在線折扣或優惠券，這些折扣或優惠券可以通過製藥公司或像 GoodRx 這樣的網站在線獲得。製藥公司的折扣有特定的資格標準，並非所有患者都能獲得（例如，醫療保險受益人不符合資格）。擁有藥物保險覆蓋的患者可能會有比本表中列出的更低的自付費用。

^{b}

List of patient populations where use should be avoided highlights common populations that may be encountered in the primary care setting and this list should therefore not be considered exhaustive of all contraindications. Clinicians should review all information available in the package insert for each medication prior to prescribing to be aware of all contraindications. In general, antiobesity medications are contraindicated among pregnant persons and individuals with known hypersensitivity to medication ingredients and are used cautiously in patients who are lactating.

^{b}

應避免使用的患者群體列表突顯了在初級護理環境中可能遇到的常見群體，因此此列表不應被視為所有禁忌症的詳盡清單。臨床醫生在開處方之前應查看每種藥物包裝插頁中提供的所有信息，以了解所有禁忌症。一般而言，抗肥胖藥物對孕婦和已知對藥物成分過敏的個體是禁忌的，並且在哺乳期患者中應謹慎使用。

^{c}

Medication is approved by the US Food and Drug Administration as Schedule IV controlled substance; therefore, prescribers need to adhere to federal and state regulations for prescribing and dispensing these types of medications.

^{c}

藥物已獲得美國食品藥品監督管理局的批准，為第四類受控物質；因此，開處方者需要遵守聯邦和州的處方及發藥規定。

^{d}

As of March 2024, package inserts for liraglutide, semaglutide, and tirzepatide include a warning about the risk of SI ; however, no increased risk of suicide has been identified in monitoring studies,

^{40}

which was acknowledged by the US Food and Drug Administration in January 2024.
截至 2024 年 3 月，利拉鲁肽、塞馬魯肽和替卡格肽的包裝插頁中包含有關自殺意念風險的警告；然而，在監測研究中並未發現自殺風險增加，這一點在 2024 年 1 月得到了美國食品藥品監督管理局的確認。
phentermine-topiramate

15 / 92 mg

reduced progression to type 2 diabetes compared with placebo.

^{50}

Patients with type 2 diabetes achieved mean weight loss of

9.4 %

and hemoglobin

A_{1 c}

reduction of

1.6 %

at 12 months with phentermine-topiramate

15 / 92 mg

compared with placebo.

^{34} A

cardiovascular outcomes trial has not been conducted for phentermine-topiramate. An observational study of the FDA Adverse Event Reporting System found no association between this medication and increased rates of cardiovascular events.

^{52}

苯丁胺-托吡酯

15 / 92 mg

與安慰劑相比，減少了 2 型糖尿病的進展。

^{50}

2 型糖尿病患者在 12 個月內使用苯丁胺-托吡酯

15 / 92 mg

時，平均體重減輕

9.4 %

，血紅蛋白

A_{1 c}

減少

1.6 %

，與安慰劑相比。

^{34} A

尚未對苯丁胺-托吡酯進行心血管結果試驗。對 FDA 不良事件報告系統的觀察研究未發現此藥物與心血管事件發生率增加之間的關聯。

^{52}

As long-term phentermine-topiramate can achieve and sustain a

10 %

weight reduction, this AOM may be useful for patients who need to meet this goal, particularly to reduce blood pressure or manage diabetes (Table 2). In clinical practice, medication adherence declined over time (

36 %

at 3 months;

13 %

at 12 months).

^{39}

Reasons for phentermine-topiramate discontinuation were not reported.

^{39}

Regular follow-up may be important for monitoring adherence. Phentermine-topiramate may be an affordable option for patients without insurance coverage (Table 3). Prescribing phentermine and topiramate separately may further reduce costs. However, clinicians and patients should be aware that this approach is an off-label use and limited clinical trial data support the approach.
只要長期使用芬特明-托吡酯能夠實現並維持

10 %

的體重減輕，這種藥物可能對需要達到這一目標的患者有用，特別是為了降低血壓或管理糖尿病（表 2）。在臨床實踐中，藥物依從性隨時間下降（

36 %

在 3 個月時；

13 %

在 12 個月時）。

^{39}

芬特明-托吡酯停用的原因未被報告。

^{39}

定期隨訪可能對監測依從性很重要。芬特明-托吡酯可能是沒有保險覆蓋的患者的一個經濟實惠的選擇（表 3）。分開開處方芬特明和托吡酯可能進一步降低成本。然而，臨床醫生和患者應該意識到這種方法是非標籤使用，並且有限的臨床試驗數據支持這種方法。

Common adverse events associated with phenterminetopiramate include paresthesia (14%-20%), dry mouth (14%

19 %

), constipation (

15 % - 16 %

), and dysgeusia (7%-9%),

^{25}

which may improve with dose reduction (Table3). Because of an increased risk of congenital fetal oral-cleft malformation from topiramate, individuals of childbearing age should have a negative pregnancy test result before treatment and should be monitored with monthly pregnancy testing as long as they take this drug. Individuals of childbearing age should also be counseled to use effective contraception consistently. Maximum dose is limited to phentermine-topiramate

7.5 / 46 mg

daily in patients with moderate kidney and mild-tomoderate hepatic impairment and the highest dose should be avoided in patients with depression/anxiety (Table 2). Phenterminetopiramate may be unavailable in other countries where regulators cite the need for long-term data regarding cardiovascular, psychiatric, and cognitive outcomes to consider approval.

^{48}

與芬特明-托吡酯相關的常見不良事件包括感覺異常（14%-20%）、口乾（14%

19 %

）、便秘（

15 % - 16 %

）和味覺障礙（7%-9%），

^{25}

這些情況可能會因減少劑量而改善（表 3）。由於托吡酯增加了先天性胎兒口腔裂隙畸形的風險，育齡女性在治療前應進行陰性妊娠測試，並在服用此藥物期間每月進行妊娠檢測。育齡女性還應被建議持續使用有效的避孕措施。對於中度腎功能不全和輕度至中度肝功能不全的患者，最大劑量限制為芬特明-托吡酯

7.5 / 46 mg

每日，並且在有抑鬱/焦慮的患者中應避免使用最高劑量（表 2）。芬特明-托吡酯在其他國家可能無法獲得，因為監管機構引用需要長期數據以考慮心血管、精神病和認知結果的批准。

^{48}

Naltrexone-Bupropion 納曲酮-布普洛尼

Naltrexone-bupropion was approved for long-term use in adults in

2014^{26}

; it has not been studied in adolescents. A meta-analysis of
納曲酮-布普利昂於

2014^{26}

獲准在成人中長期使用；尚未在青少年中進行研究。一項綜合分析的

6 RCTs that included 9949 adults with obesity reported that nal-trexone-bupropion was associated with

4.1 %

greater weight loss than placebo (

95 % Cl, 3.0 % - 5.2 %

^{15}

Combining naltrexone-bupropion with intensive behavioral therapy was associated with

9.3 %

weight loss at 12 months, compared with

5.1 %

weight loss for placebo combined with intensive behavioral therapy.

^{53}

Nearly half of naltrexonebupropion participants achieved

5 %

or greater weight loss in another 56-week RCT (Figure 2).

^{18}

6 項隨機對照試驗（RCT）包括 9949 名肥胖成年人，報告顯示納曲酮-布普洛尼與安慰劑相比，體重減輕

4.1 %

更顯著（

95 % Cl, 3.0 % - 5.2 %

）。

^{15}

將納曲酮-布普洛尼與強化行為療法結合，在 12 個月時的體重減輕為

9.3 %

，而安慰劑結合強化行為療法的體重減輕為

5.1 %

。

^{53}

在另一項為期 56 週的 RCT 中，近一半的納曲酮-布普洛尼參與者達到了

5 %

或更大的體重減輕（圖 2）。

^{18}

Compared with other AOMs, naltrexone-bupropion has fewer effects on cardiovascular risk factors (Table 1; eTable 3 in the Supplement).

^{18, 35, 53, 54}

Among patients with hypertension, naltrexonebupropion had no significant effect on blood pressure compared with placebo.

^{30}

Bupropion is known to increase blood pressure.

^{55}

In contrast, other AOMs, such as orlistat and phentermine-topiramate, have lowered blood pressure among patients with hypertension.

^{30}

Patients with type 2 diabetes achieved mean weight loss of

5.0 %

and hemoglobin

A_{1 c}

reduction of

0.6 %

at 12 months with naltrexonebupropion compared with placebo.

^{35} An

RCT that included 8910 people reported no significant effects of naltrexone-bupropion on major adverse cardiovascular events (MACE) compared with placebo.

^{56}

與其他抗肥胖藥物相比，納曲酮-布普洛尼對心血管風險因素的影響較小（表 1；補充資料中的 e 表 3）。在高血壓患者中，納曲酮-布普洛尼對血壓沒有顯著影響，與安慰劑相比。布普洛尼已知會增加血壓。相反，其他抗肥胖藥物，如奧利司他和芬特明-托吡酯，則在高血壓患者中降低了血壓。2 型糖尿病患者在使用納曲酮-布普洛尼後，與安慰劑相比，在 12 個月內實現了平均體重減輕和血紅蛋白的降低。包括 8910 人的隨機對照試驗報告顯示，納曲酮-布普洛尼對主要不良心血管事件（MACE）沒有顯著影響，與安慰劑相比。

Weight reduction is greater when naltrexone-bupropion is combined with intensive behavioral therapy. Therefore, it may be best suited for patients participating in intensive behavioral programs, in which monitoring of blood pressure during initiation and dose escalation can more easily occur. Naltrexone-bupropion is less expensive than other AOMs for patients who lack insurance coverage (Table 3). Prescribing naltrexone and bupropion separately may further reduce costs. However, this approach is an off-label use and limited trial data support the approach. In clinical practice, medication adherence is relatively low (

34 %

at 3 months;

10 %

at 12 months).

^{39}

Reasons for naltrexone-bupropion discontinuation were not reported.

^{39}

當納曲酮-布普洛尼與強化行為療法結合時，體重減輕的效果更顯著。因此，這可能最適合參加強化行為計劃的患者，在這些計劃中，啟動和劑量增加期間的血壓監測可以更容易進行。對於缺乏保險覆蓋的患者，納曲酮-布普洛尼的成本低於其他抗肥胖藥物（表 3）。分開開處方納曲酮和布普洛尼可能進一步降低成本。然而，這種方法屬於非標籤使用，且有限的試驗數據支持該方法。在臨床實踐中，藥物依從性相對較低（

34 %

在 3 個月時；

10 %

在 12 個月時）。

^{39}

未報告納曲酮-布普洛尼中斷的原因。

^{39}

Common adverse effects of naltrexone-bupropion include nausea (33%), constipation (19%), headache (18%), vomiting (11%), dizziness (

10 %

), insomnia (

9 %

), and xerostomia (

8 %)^{26}

and dose adjustment may be needed to address tolerability (Table 3). The maximum dose is limited to naltrexone-bupropion

8 / 90 mg

daily in patients with moderate kidney and mild to moderate hepatic impairment, and naltrexone-bupropion should be avoided in young adults with depression/anxiety (Table 2).
納曲酮-布普利昂的常見不良反應包括噁心（33%）、便秘（19%）、頭痛（18%）、嘔吐（11%）、頭暈（

10 %

）、失眠（

9 %

）和口乾（

8 %)^{26}

，可能需要調整劑量以應對耐受性（表 3）。對於中度腎功能和輕度至中度肝功能損害的患者，最大劑量限制為每日納曲酮-布普利昂

8 / 90 mg

，並且應避免在有抑鬱/焦慮的年輕成年人中使用納曲酮-布普利昂（表 2）。

Nutrient-Stimulated Hormone-Based Medications
營養刺激激素基藥物

The discovery of the role of the gut-brain axis in controlling appetite has provided new biological targets for drug development, nutrient-stimulated hormone-based medications, which simulate the metabolic effects of naturally occurring entero-pancreatic hormones,

^{57}

including glucagon-like peptide-1 (GLP-1),

^{58}

glucosedependent insulinotropic polypeptide (GIP),

^{59}

glucagon,

^{60}

and amylin.

^{61}

GLP-1 receptor agonists (RAs) have been the most studied given their incretin effect (ie, amplified insulin secretion after oral vs intravenous glucose administration) and other pleiotropic cardiometabolic actions (eg, decreased blood pressure and inflammation) that are mediated by the widespread distribution of GLP-1 receptors throughout the body.

^{62}

GLP-1 RAs were initially introduced for type 2 diabetes treatment and more recently for obesity treatment. Entero-pancreatic hormones, such as GLP-1, GIP, and glucagon, can have complementary or distinct biological activity that supports development of combination medications. For example, in addition to enhancing appetite suppression, GIP recep-
腸腦軸在控制食慾中的作用的發現為藥物開發提供了新的生物學靶點，基於營養刺激的激素藥物模擬自然存在的腸胰激素的代謝效應，包括胰高血糖素樣肽-1 (GLP-1)、葡萄糖依賴性胰島素促進多肽 (GIP)、胰高血糖素和澱粉酶。GLP-1 受體激動劑 (RAs) 由於其促胰島素效應（即口服與靜脈注射葡萄糖給藥後的胰島素分泌增強）和其他多重心血管代謝作用（例如，降低血壓和炎症）而成為最受研究的藥物，這些作用是由 GLP-1 受體在全身的廣泛分佈所介導的。GLP-1 RAs 最初是為了治療 2 型糖尿病而引入的，最近則用於治療肥胖。腸胰激素，如 GLP-1、GIP 和胰高血糖素，可能具有互補或不同的生物活性，支持組合藥物的開發。例如，除了增強食慾抑制外，GIP 受體
tors exist in adipose tissue to promote lipoprotein lipase activation.

^{63}

Glucagon enhances hepatic lipolysis and may increase energy expenditure,

^{64}

whereas amylin enhances leptin sensitization and has direct brain activation to promote meal-ending satiety.

^{61}

Nutrientstimulated hormone-based medications represent a paradigm shift in the pharmacological treatment of obesity given their weightloss efficacy, safety, and indirect beneficial effects on cardiometabolic and kidney disease risk factors.

^{65}

脂肪組織中存在轉運蛋白以促進脂蛋白脂肪酶的活化。

^{63}

胰高血糖素增強肝臟脂解並可能增加能量消耗，

^{64}

而胰淀粉酶增強瘦素敏感性並直接激活大腦以促進餐後飽足感。

^{61}

營養刺激的基於激素的藥物代表了肥胖藥物治療的範式轉變，因為它們在減重效果、安全性以及對心代謝和腎臟疾病風險因素的間接有益影響方面具有優勢。

^{65}

The FDA has approved 3 nutrient-stimulated hormone-based AOMs: liraglutide, semaglutide, and tirzepatide. As the half-life of native GLP-1 is only 2 to 3 minutes due to rapid degradation by dipeptidyl peptidase IV (DPP-4), these AOMs have modified structure to resist DPP-4 proteolysis and prolong half-life.

^{65}

Liraglutide is a GLP-1 RA with

97 %

homology to human GLP-1 with reduced susceptibility to DPP-4 that increases half-life to 11 to 15 hours with daily subcutaneous administration.

^{27, 66}

Semaglutide is another GLP-1 RA that is designed for weekly subcutaneous administration, with a 183 -hour half-life.

^{28, 67}

Tirzepatide is a dual GIP/GLP-1 RA with a 117-hour halflife with weekly subcutaneous administration.

^{29, 68} GIP

appears to act synergistically with GLP-1 in the brain to promote a greater magnitude of weight loss compared with GLP-1 alone.
FDA 已批准三種以營養刺激的激素為基礎的 AOMs：利拉魯肽、塞馬魯肽和替卡魯肽。由於內源性 GLP-1 的半衰期僅為 2 到 3 分鐘，因為它會被二肽基肽酶 IV (DPP-4) 快速降解，這些 AOMs 具有改良的結構以抵抗 DPP-4 蛋白水解並延長半衰期。利拉魯肽是一種 GLP-1 RA，與人類 GLP-1 具有同源性，對 DPP-4 的敏感性降低，半衰期延長至 11 到 15 小時，通過每日皮下注射給藥。塞馬魯肽是另一種 GLP-1 RA，設計用於每週皮下注射，半衰期為 183 小時。替卡魯肽是一種雙重 GIP/GLP-1 RA，半衰期為 117 小時，通過每週皮下注射給藥。它似乎在大腦中與 GLP-1 協同作用，促進比單獨使用 GLP-1 更大的減重效果。

Liraglutide 利拉魯肽

Liraglutide was approved for obesity treatment in 2014 for adults and in 2020 for adolescents (aged

\geq 12

years) (maximum dose, 3.0 mg daily).

^{27}

A meta-analysis of 18 RCTs that included 6321 participants reported that, compared with placebo, liraglutide was associated with a

4.7 %

weight reduction (

95 % Cl, 4.1 % - 5.3 %

) among adults with obesity. The meta-analysis included RCTs for both type 2 diabetes and obesity treatment.

^{15}

Specifically targeting obesity, liraglutide has been studied in 5 RCTs (Satiety and Clinical Adiposity - Liraglutide Evidence [SCALE] trials) involving more than 5000 adults to evaluate its efficacy and safety (eTable 4 in the Supplement).

^{19, 36, 69 - 71}

More than

60 %

of participants treated with liraglutide achieved 5% or greater weight loss (Figure 2).

^{19}

The SCALE trials’ intention-to-treat 1 -year weight loss ranged from

3.4 %

6.1 %

compared with placebo. In a trial of adolescents with obesity, liraglutide attained a mean BMI reduction of

5 %

compared with placebo.

^{72}

利拉鲁肽於 2014 年獲准用於成人的肥胖治療，並於 2020 年獲准用於青少年（年齡

\geq 12

歲）（最大劑量，3.0 毫克每日）。

^{27}

一項包含 6321 名參與者的 18 項隨機對照試驗（RCT）的綜合分析報告顯示，與安慰劑相比，利拉魯肽與成人肥胖患者的

4.7 %

體重減輕（

95 % Cl, 4.1 % - 5.3 %

）相關。該綜合分析包括針對 2 型糖尿病和肥胖治療的 RCT。

^{15}

專門針對肥胖，利拉魯肽在 5 項 RCT（飽腹感與臨床脂肪 - 利拉魯肽證據[SCALE]試驗）中進行研究，涉及超過 5000 名成人，以評估其療效和安全性（補充資料中的 eTable 4）。

^{19, 36, 69 - 71}

超過

60 %

的利拉魯肽治療參與者達到 5%或更高的體重減輕（圖 2）。

^{19}

SCALE 試驗的意向治療 1 年體重減輕範圍為

3.4 %

至

6.1 %

，與安慰劑相比。在一項針對肥胖青少年的試驗中，利拉魯肽與安慰劑相比達到了平均 BMI 減少

5 %

。

^{72}

Liraglutide reduced waist circumference by approximately 8 cm , decreased SBP by approximately 4 mm Hg , and reduced LDL-C by approximately

8 %

among adults with obesity (Table 1).

^{19}

Among patients with type 2 diabetes, a higher dose of liraglutide for obesity (ie,

3.0 mg / d

) did not attain greater reductions in hemoglobin

A_{1 c}

relative to a lower dose (ie,

1.8 mg / d

) for treatment of type 2 diabetes (eTable 4 in the Supplement).

^{36}

Liraglutide 3.0 mg resulted in mean weight loss of

6.0 %

and mean hemoglobin

A_{1 c}

decrease of

1.6 %

among adults with type 2 diabetes and obesity.

^{36}

An RCT of 9340 participants with type 2 diabetes reported liraglutide reduced MACE compared with placebo.

^{73} A

similar clinical trial has not been conducted in patients with obesity and without type 2 diabetes.

^{74}

利拉鲁肽使肥胖成人的腰圍減少約 8 厘米，收縮壓減少約 4 毫米汞柱，低密度脂蛋白膽固醇減少約

8 %

（見表 1）。

^{19}

在 2 型糖尿病患者中，為肥胖使用的較高劑量利拉魯肽（即

3.0 mg / d

）未能相對於較低劑量（即

1.8 mg / d

）在治療 2 型糖尿病方面達到更大的血紅蛋白

A_{1 c}

減少（見補充資料中的 eTable 4）。

^{36}

利拉魯肽 3.0 毫克使 2 型糖尿病和肥胖成人的平均體重減輕

6.0 %

，平均血紅蛋白

A_{1 c}

減少

1.6 %

。

^{36}

一項包含 9340 名 2 型糖尿病參與者的隨機對照試驗報告顯示，利拉魯肽相比安慰劑減少了主要不良心血管事件（MACE）。

^{73} A

在沒有 2 型糖尿病的肥胖患者中尚未進行類似的臨床試驗。

^{74}

Liraglutide may be a reasonable option for patients with coexisting type 2 diabetes (Table 2) when other nutrient-stimulated hor-mone-based AOMs are not covered by insurance or for patients who prefer to use a medication from this class, which has been on the market longest. In real-world settings, medication adherence declined over time (

52 %

at 3 months; 17% at 12 months).

^{39}

Reasons for liraglutide discontinuation were not reported.

^{39}

Regular follow-up may be important to maximize adherence long-term.
利拉鲁肽可能是合併有 2 型糖尿病的患者的合理選擇（表 2），當其他營養刺激的激素類抗肥胖藥物未被保險覆蓋或患者更願意使用這類已上市最久的藥物時。在現實世界中，藥物依從性隨時間下降（

52 %

在 3 個月時；12 個月時為 17%）。

^{39}

利拉魯肽停藥的原因未被報告。

^{39}

定期隨訪可能對於最大化長期依從性很重要。

The most common adverse effects associated with liraglutide are nausea (39%), diarrhea (21%), and constipation (19%), which are mild to moderate and occur primarily during the dose escalation phase.

^{27}

Table 3 includes additional practical considerations in prescribing and managing liraglutide.
與利拉魯肽相關的最常見不良反應是噁心（39%）、腹瀉（21%）和便秘（19%），這些反應輕微到中等，主要發生在劑量增加階段。

^{27}

表 3 包含了在開處方和管理利拉魯肽時的其他實用考量。

Semaglutide

Semaglutide was approved for chronic weight management in 2021 for adults and in 2022 for adolescents (aged

\geq 12

years) (maximum dose, 2.4 mg weekly).

^{28}

Semaglutide 2.4 mg was also approved to reduce the risk of MACE in adults with established cardiovascular disease and either obesity or overweight in 2024. A meta-analysis of 5 RCTs that included 4421 participants reported an 11.4% greater weight loss than placebo (

95 % Cl, 10.3 % - 12.5 %

) among adults treated for obesity.

^{15}

The Semaglutide Treatment Effect in People with Obesity Program (STEP) included multiple RCTs comparing semaglutide 2.4 mg and placebo on weight loss, safety, and tolerability in adults (eTable 5 in the Supplement).

^{20, 37, 75 - 80}

Compared with placebo, weight loss ranged from

6.2 %

14.8 %

at 68 -week follow-up in STEP 1-4

^{20, 37.76 .77}

and

12.6 %

at 2 years in STEP

5 .^{78}

More than

85 %

of participants taking semaglutide attained

5 %

or greater weight loss (Figure 2).

^{20}

When directly compared, weight loss was

15.8 %

for semaglutide and

6.4 %

for liraglutide.

^{80}

In an RCT of adolescents with obesity, semaglutide attained a

16.1 %

BMI reduction compared with a

0.6 % BMI

increase for placebo.

^{81}

Semaglutide 於 2021 年獲准用於成人的慢性體重管理，2022 年獲准用於青少年（年齡

\geq 12

歲）（最大劑量為每週 2.4 毫克）。

^{28}

Semaglutide 2.4 毫克於 2024 年也獲准用於降低患有既往心血管疾病且有肥胖或超重的成人的 MACE 風險。一項包含 4421 名參與者的 5 項隨機對照試驗（RCT）的綜合分析報告顯示，接受肥胖治療的成人比安慰劑的體重減輕多 11.4%（

95 % Cl, 10.3 % - 12.5 %

）。

^{15}

Semaglutide 肥胖治療效果計劃（STEP）包括多項 RCT，對比了 Semaglutide 2.4 毫克和安慰劑在成人的體重減輕、安全性和耐受性方面的效果（補充資料中的 eTable 5）。

^{20, 37, 75 - 80}

與安慰劑相比，STEP 1-4 的 68 週隨訪中體重減輕範圍為

6.2 %

至

14.8 %

，而在 STEP 的 2 年隨訪中為

^{20, 37.76 .77}

和

12.6 %

。超過

85 %

的 Semaglutide 參與者達到了

5 %

或更大的體重減輕（圖 2）。

^{20}

直接比較時，Semaglutide 的體重減輕為

15.8 %

，而 Liraglutide 為

6.4 %

。在一項針對肥胖青少年的 RCT 中，Semaglutide 實現了

16.1 %

的 BMI 減少，而安慰劑則增加了

0.6 % BMI

。

^{81}

Semaglutide reduced waist circumference by approximately 14 cm and SBP by approximately 6 mm Hg (Table 1).

^{20.76}

Semaglutide 2.4 mg resulted in mean weight loss of

9.6 %

and mean hemoglobin

A_{1 c}

decrease of

1.6 %

among adults with type 2 diabetes and obesity.

^{37}

In the Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial, semaglutide 2.4 mg reduced MACE by 20% compared with placebo (absolute rates of MACE: semaglutide, 6.5%; placebo, 8.0%) in 17604 adults with BMI of 27 or greater and preexisting cardiovascular disease without type 2 diabetes.

^{82}

In an RCT of 529 participants with obesity and heart failure with preserved ejection fraction, semaglutide 2.4 mg reduced heart failure symptoms and body weight as well as increased 6 -minute walk distance and reduced C -reactive protein levels compared with placebo.

^{83}

Semaglutide 使腰圍減少約 14 公分，收縮壓減少約 6 毫米汞柱（表 1）。

^{20.76}

Semaglutide 2.4 毫克使患有 2 型糖尿病和肥胖的成年人平均減重

9.6 %

，平均血紅蛋白

A_{1 c}

減少

1.6 %

。

^{37}

在 Semaglutide 對超重或肥胖人群心血管結果的影響（SELECT）試驗中，Semaglutide 2.4 毫克使主要心血管不良事件（MACE）較安慰劑減少 20%（MACE 的絕對比率：Semaglutide 6.5%；安慰劑 8.0%），參與者為 17604 名 BMI 大於或等於 27 且有既往心血管疾病但無 2 型糖尿病的成年人。

^{82}

在一項針對 529 名有肥胖和保留射血分數心衰竭的參與者的隨機對照試驗中，Semaglutide 2.4 毫克減少了心衰症狀和體重，並增加了 6 分鐘步行距離，同時降低了 C 反應蛋白水平，與安慰劑相比。

^{83}

Because semaglutide achieves and sustains greater than 10% weight reduction while therapy is continued, this AOM may be most appropriate for patients who need to meet this goal, particularly among patients with multiple weight-related conditions (Table 2). In contrast with other AOMs, medication adherence with semaglutide remained relatively high over time in real-world settings (

63 %

at 3 months;

40 %

at 12 months).

^{39}

因為 semaglutide 在治療期間能夠達到並維持超過 10% 的體重減輕，因此這種 AOM 可能最適合需要達成這一目標的患者，特別是在多種與體重相關的疾病患者中（表 2）。與其他 AOM 相比，semaglutide 在現實世界環境中的用藥依從性隨時間保持相對較高（

63 %

在 3 個月；

40 %

在 12 個月）。

^{39}

Common adverse effects of semaglutide include nausea (44%), diarrhea (30%), vomiting (24%), constipation (24%), and abdominal pain (20%),

^{28}

which are mild to moderate and mostly occur during dose escalation.

^{84}

Nausea, diarrhea, and vomiting typically subside within a week; however, constipation may last approximately 45 days.

^{84}

Counseling patients at initiation on key dietary modifications, such as decreased portion sizes, reduced fat, and increased dietary fiber intake, may help mitigate these Gl effects (Table 3).
Semaglutide 的常見不良反應包括噁心（44%）、腹瀉（30%）、嘔吐（24%）、便秘（24%）和腹痛（20%），

^{28}

這些反應通常是輕度到中度，並且大多發生在劑量增加期間。

^{84}

噁心、腹瀉和嘔吐通常在一週內緩解；然而，便秘可能持續約 45 天。

^{84}

在開始治療時對患者進行關於關鍵飲食調整的諮詢，例如減少食物份量、降低脂肪攝入和增加膳食纖維攝入，可能有助於減輕這些 Gl 反應（表 3）。

Tirzepatide

Tirzepatide was approved to treat obesity in adults in

2023 .^{29}

A metaanalysis of 6 RCTs that included 1972 participants reported that tirz-
Tirzepatide 獲准用於治療成人肥胖症於

2023 .^{29}

一項包含 1972 名參與者的 6 項隨機對照試驗的綜合分析報告顯示，tirz-
epatide 15 mg was associated with

12.4 %

greater weight loss than placebo (

95 % Cl, 7.5 % - 17.2 %

) among adults with obesity, which included RCTs for both type 2 diabetes and obesity treatment.

^{85}

In multiple RCTs in the SURMOUNT program,

^{86}

weight loss ranged from

11.6 %

21.4 %

with tirzepatide 15 mg , compared with placebo, among adults with obesity (eTable 6 in the Supplement).

^{21, 38, 87, 88}

More than

90 %

of participants treated with tirzepatide 15 mg achieved 5% or greater weight loss (Figure 2).

^{21}

epatide 15 mg 與安慰劑相比，在肥胖成人中與

12.4 %

的體重減輕相關（

95 % Cl, 7.5 % - 17.2 %

），這包括針對 2 型糖尿病和肥胖治療的隨機對照試驗（RCTs）。在 SURMOUNT 計劃的多項 RCT 中，

^{86}

使用 tirzepatide 15 mg 的體重減輕範圍從

11.6 %

到

21.4 %

，與安慰劑相比，針對肥胖成人（補充資料中的 eTable 6）。

^{21, 38, 87, 88}

超過

90 %

的接受 tirzepatide 15 mg 治療的參與者達到了 5%或更高的體重減輕（圖 2）。

^{21}

Dose-dependent improvements were seen with tirzepatide for multiple cardiometabolic outcomes (eTable 6 in the Supplement).

^{21, 38, 87, 88}

For example, tirzepatide 15 mg reduced waist circumference by approximately 19 cm , decreased SBP by approximately 8 mm Hg , and reduced LDL-C by

9 %

(Table 1).

^{21}

Tirzepatide 15 mg resulted in mean weight loss of

14.7 %

and mean hemoglobin

A_{1 c}

decrease of

2.1 %

among adults with type 2 diabetes and obesity.

^{38}

A randomized clinical trial testing the effects of tirzepatide on cardiovascular outcomes among adults with obesity is ongoing.

^{89}

隨著劑量的增加，使用 tirzepatide 在多個心臟代謝結果上觀察到了改善（補充資料中的 eTable 6）。例如，15 毫克的 tirzepatide 使腰圍減少約 19 公分，收縮壓減少約 8 毫米汞柱，並使 LDL-C 減少

9 %

（表 1）。15 毫克的 tirzepatide 在患有 2 型糖尿病和肥胖的成年人中導致平均體重減輕

14.7 %

，平均血紅蛋白

A_{1 c}

減少

2.1 %

。一項隨機臨床試驗正在進行中，旨在測試 tirzepatide 對肥胖成年人心血管結果的影響。

Similar to semaglutide, tirzepatide should be prescribed to adults needing to achieve greater weight reductions, particularly patients with greater weight-related morbidity (Table 2). Although there are no direct comparisons, tirzepatide 10 mg and 15 mg showed greater weight loss than semaglutide

2.4 mg .^{90}

類似於塞馬魯肽，特爾扎肽應該處方給需要達到更大體重減輕的成年人，特別是那些有較高體重相關疾病的患者（表 2）。雖然沒有直接比較，但特爾扎肽 10 毫克和 15 毫克的體重減輕效果優於塞馬魯肽

2.4 mg .^{90}

Adverse effects of tirzepatide are dose-dependent, and commonly include nausea (

25 % - 29 %

), diarrhea (

19 % - 23 %

), constipation (11%-17%), and vomiting (8%-13%).

^{29}

These adverse effects typically occur during the dose escalation period and are primarily mild to moderate in severity (Table 3).
tirzepatide 的不良反應與劑量有關，常見的包括噁心（

25 % - 29 %

）、腹瀉（

19 % - 23 %

）、便秘（11%-17%）和嘔吐（8%-13%）。

^{29}

這些不良反應通常發生在劑量增加期間，主要為輕度至中度的嚴重程度（表 3）。

AOMs in Development 開發中的 AOMs

Combinations of nutrient-stimulated hormone-based medications (dual- and tri-agonists) are currently undergoing study among adults with obesity.

^{91}

In a phase 1 lb study of 96 participants (mean BMI, 32.1), semaglutide 2.4 mg combined with cagrilintide 2.4 mg , a longacting amylin analogue, resulted in mean weight loss of

17.1 %

at 20 week follow-up, compared with

9.5 %

for semaglutide alone.

^{92}

In a phase 2 trial of 387 participants, a dual glucagon/GLP-1 RA, survodutide, attained weight loss of

14.9 %

at the

4.8 - mg

dose, compared with

2.8 %

for placebo at 46 weeks.

^{93}

In a phase 2 trial of 338 participants, a tri-agonist RA for GIP/GLP-1/glucagon, retatrutide, attained a mean weight loss of

24.2 %

for the 12 - mg dose at 24 -week follow-up, compared with

2.1 %

for placebo.

^{94}

目前正在研究營養刺激的激素基藥物（雙重和三重激動劑）在肥胖成年人中的組合。

^{91}

在一項 96 名參與者（平均 BMI 為 32.1）的第一階段研究中，2.4 毫克的 semaglutide 與 2.4 毫克的 cagrilintide（一種長效胰島素類似物）結合，結果在 20 週的隨訪中平均減重

17.1 %

，而單獨使用 semaglutide 的減重為

9.5 %

。

^{92}

在一項 387 名參與者的第二階段試驗中，雙重胰高血糖素/GLP-1 RA，survodutide，在

4.8 - mg

劑量下達到

14.9 %

的減重，而安慰劑在 46 週的減重為

2.8 %

。

^{93}

在一項 338 名參與者的第二階段試驗中，針對 GIP/GLP-1/胰高血糖素的三重激動劑 RA，retatrutide，在 24 週的隨訪中達到 12 毫克劑量的平均減重

24.2 %

，而安慰劑的減重為

2.1 %

。

^{94}

Orally administered nutrient-stimulated hormone-based AOMs are being studied in adults with obesity.

^{91}

In a clinical trial of 667 participants, oral semaglutide 50 mg daily attained weight loss of

12.7 %

(

95 % Cl, - 14.2 %

- 11.3 %

), compared with placebo.

^{95}

In a phase 2 trial of 272 participants, an oral nonpeptide GLP-1 RA, orforglipron, attained weight reduction of

14.7 %

, compared with

2.3 %

for placebo, at 36 -week follow-up.

^{96}

口服給藥的營養刺激激素基礎的 AOM 正在對肥胖成人進行研究。在一項包含 667 名參與者的臨床試驗中，口服塞馬格魯肽 50 毫克每日達到的體重減輕為

12.7 %

（

95 % Cl, - 14.2 %

至

- 11.3 %

），與安慰劑相比。在一項包含 272 名參與者的第二階段試驗中，口服非肽 GLP-1 RA，奧福格利普隆，達到的體重減輕為

14.7 %

，與安慰劑的

2.3 %

相比，在 36 週的隨訪中。

New therapies with mechanisms of action that differ from nu-trient-stimulated hormone-based therapeutics are in development. For example, an antibody that blocks activin type II receptors, bimagrumab, caused significant fat mass loss and gain in muscle mass.

^{97}

A multicenter RCT to determine the efficacy and safety of 24-month phentermine use is ongoing.

^{98}

新的療法正在開發中，其作用機制與營養刺激的激素基療法不同。例如，阻止活化素 II 型受體的抗體 bimagrumab，導致顯著的脂肪質量損失和肌肉質量增加。

^{97}

一項多中心隨機對照試驗正在進行，以確定 24 個月使用苯丁胺的療效和安全性。

^{98}

Lifestyle Change and AOMs
生活方式改變與 AOMs

All AOMs are approved as adjunctive therapy to a reduced-calorie diet and increased physical activity. Clinicians should counsel patients
所有 AOM 均被批准作為減少卡路里飲食和增加體力活動的輔助療法。臨床醫生應該對患者進行諮詢。
on these lifestyle modifications at the time of AOM initiation and recommend a strategy for patients to engage monthly with a lifestyle program or trained health care professional (eg, dietitian, health coach). Important nutritional recommendations exist for specific AOMs, such as avoiding a high-fat diet with orlistat or naltrexonebupropion (Table 3).
在急性中耳炎（AOM）開始時進行這些生活方式的改變，並建議患者每月參加生活方式計劃或與受過訓練的醫療專業人員（例如，營養師、健康教練）互動。對於特定的 AOM，存在重要的營養建議，例如避免與奧利司他或納曲酮-布普品（naltrexone-bupropion）一起使用的高脂飲食（表 3）。

Outcomes improve when AOMs, particularly naltrexonebupropion, are combined with intensive behavioral therapy

^{53}

(12-26 multicomponent sessions over 12 months).

^{53}

The US Preventive Services Task Force recommends intensive behavioral therapy,

^{99}

which is covered by Medicare and Medicaid programs in many states. Intensive behavioral therapy may be less important in conjunction with semaglutide or tirzepatide,

^{76, 87}

as their appetite suppression efficacy make it easier for patients to reduce food intake without feeling deprived. With semaglutide and tirzepatide, clinicians may focus counseling on healthy eating patterns and food quality,

^{100}

prioritizing lean proteins and increasing consumption of fruits, vegetables, and complex carbohydrates.
當 AOMs，特別是納曲酮-布普品，與強化行為療法結合時，結果會改善

^{53}

（在 12 個月內進行 12-26 次多組件會議）。

^{53}

美國預防服務工作組建議進行強化行為療法，

^{99}

這在許多州的醫療保險和醫療補助計劃中都有涵蓋。與 semaglutide 或 tirzepatide 結合時，強化行為療法可能不那麼重要

^{76, 87}

，因為它們的食慾抑制效果使患者更容易減少食物攝入而不感到被剝奪。使用 semaglutide 和 tirzepatide 時，臨床醫生可以將諮詢重點放在健康飲食模式和食物質量上，

^{100}

優先考慮瘦蛋白並增加水果、蔬菜和複雜碳水化合物的攝入。

Safety of AOMs AOMs 的安全性

Clinicians should discuss the adverse effect profiles of AOMs with patients. Since 2012, FDA regulations require that AOMs be evaluated for cardiovascular safety,

^{101}

and postmarketing surveillance studies are ongoing to update adverse effects profiles based on use in clinical practice. Clinicians should review up-to-date prescribing information on manufacturer websites. Given their varying mechanisms, clinicians should examine the risk-benefit profile of each AOM individually.

^{102}

臨床醫生應與患者討論 AOM 的副作用概況。自 2012 年以來，FDA 規定要求對 AOM 進行心血管安全性評估，

^{101}

並且正在進行上市後監測研究，以根據臨床實踐中的使用情況更新副作用概況。臨床醫生應查看製造商網站上的最新處方信息。鑑於它們的機制各異，臨床醫生應單獨檢查每種 AOM 的風險收益概況。

^{102}

One particular concern is maintaining lean body mass (muscle mass) during weight loss that is important for mobility and physical function, particularly among older adults who have a lower lean body mass due to aging. AOMs should be used in adults aged 65 years or older with caution.

^{7}

Clinicians’ physical activity counseling should integrate resistance training (eg, weight lifting, resistance bands) to decrease lean body mass loss and enhance functional strength and mobility.

^{103}

Aerobic activity alone is typically insufficient to preserve lean body mass. Physical activity is also important for maintaining weight loss.

^{104}

一個特別的擔憂是在減重過程中維持瘦體重（肌肉量），這對於行動能力和身體功能非常重要，特別是在因為衰老而擁有較低瘦體重的老年人中。對於 65 歲或以上的成年人，應謹慎使用 AOMs。

^{7}

醫療人員的身體活動諮詢應整合抗阻訓練（例如，舉重、阻力帶），以減少瘦體重的損失並增強功能性力量和行動能力。

^{103}

單靠有氧運動通常不足以維持瘦體重。身體活動對於維持體重減輕也很重要。

^{104}

AOMs are typically contraindicated among pregnant persons and should be avoided in patients who are lactating.

^{6}

Use of reliable contraception among persons with pregnancy potential is recommended. Preconception planning is important because AOMs have different recommended durations of discontinuation before conception. For example, semaglutide should be discontinued at least 2 months before pregnancy is attempted.
AOMs 通常對孕婦是禁忌的，並應避免在哺乳期的患者中使用。

^{6}

建議有懷孕潛力的人使用可靠的避孕措施。孕前規劃很重要，因為 AOMs 在懷孕前有不同的建議停藥時間。例如，semaglutide 應在嘗試懷孕前至少停用 2 個月。

Duration of AOM Use
AOM 使用的持續時間

In primary care settings, AOM use increases the proportion of patients achieving

5 %

or greater weight loss.

^{105}

However, realworld studies have found poor medication adherence in clinical practice.

^{106}

Due to the counter-regulatory metabolic changes that occur with weight reduction, such as reduced metabolic rate and increased appetite, weight gain is common when AOMs are discontinued.

^{77, 88, 107}

Clinicians should use shared decisionmaking to determine medication duration, such as continuing an AOM long-term on the lowest effective dose, using intermittent therapy, or stopping medication followed by close weight monitoring (Box).
在初級護理環境中，AOM 的使用增加了達到

5 %

或更大體重減輕的患者比例。

^{105}

然而，現實世界的研究發現臨床實踐中的藥物依從性較差。

^{106}

由於體重減輕時發生的反調節代謝變化，例如代謝率降低和食慾增加，停用 AOM 後體重增加是常見的。

^{77, 88, 107}

醫生應該使用共享決策來確定藥物的使用期限，例如在最低有效劑量下長期持續使用 AOM、使用間歇性療法，或停止用藥後進行密切的體重監測（見框）。

Box. Common Questions 盒子。常見問題

Who is eligible for treatment with an antiobesity medication (AOM)? AOMs are approved as adjunctive therapy to lifestyle change in adults with an initial body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 30 or greater (obesity) or 27 or greater (overweight) in the presence of at least 1 weight-related comorbid condition. Adolescents (aged 12 years or older) with BMI $\geq 95$ th percentile for age and sex may be considered for some AOMs (orlistat, phentermine-topiramate, liraglutide, and semaglutide).
誰有資格接受抗肥胖藥物（AOM）的治療？AOM 被批准作為成人在體重指數（BMI，計算方式為體重（公斤）除以身高（米）的平方）為 30 或更高（肥胖）或 27 或更高（超重）且至少有 1 種與體重相關的合併症的情況下，輔助生活方式改變的療法。年齡在 12 歲或以上的青少年，若其 BMI 在年齡和性別的第 $\geq 95$ 百分位數，則可考慮使用某些 AOM（奧利司他、芬特明-托吡酯、利拉魯肽和塞馬魯肽）。
How long can one continue receiving AOMs?
一個人可以持續接收 AOM 多久？

AOMs are approved for chronic weight management and are often needed to maintain weight reduction long-term. Patients should be continuously monitored for drug effectiveness, tolerability, adverse effects, and the need for dose modification (escalation or de-escalation). Clinicians should engage patients in shared deci-sion-making to determine AOM duration.
AOMs 獲准用於慢性體重管理，並且通常需要長期維持體重減輕。患者應持續監測藥物的有效性、耐受性、不良反應以及劑量調整（增加或減少）的需求。臨床醫生應與患者共同參與決策，以確定 AOM 的使用期限。
3. How can the adverse gastrointestinal effects of glucagon-like peptide 1 (GLP-1) receptor agonists be reduced?
3. 如何減少胰高血糖素樣肽-1 (GLP-1) 受體激動劑的不良胃腸道影響？
Clinicians may consider a slow dose escalation as well as counseling on lifestyle strategies (eg, diet changes) to mitigate adverse effects from GLP-1 receptor agonists. Dietary counseling, including decreased portion size, reduced fat, and increased dietary fiber intake, is particularly important to help manage the gastrointestinal adverse effects of GLP-1 receptor agonists.
臨床醫生可能會考慮緩慢增加劑量以及針對生活方式策略（例如，飲食改變）的諮詢，以減輕 GLP-1 受體激動劑的不良反應。飲食諮詢，包括減少份量、降低脂肪和增加膳食纖維攝入，對於幫助管理 GLP-1 受體激動劑的胃腸道不良反應尤其重要。

Insurance Coverage and Affordability
保險覆蓋範圍和可負擔性
Many people in the US lack insurance coverage for AOMs. Medicare does not cover AOMs to treat obesity alone-it may cover an AOM that is FDA-approved and used for obesity combined with another condition (ie, semaglutide was recently approved for cardiovascular risk reduction among those with overweight or obesity and preexisting cardiovascular disease). Medicare may cover nutrient-stimulated hor-mone-based medications to treat type 2 diabetes. AOMs are covered by Medicaid in only a few states.

^{108}

Employer-sponsored health insurance often excludes coverage for AOMs as well.

^{109.110}

Consequently, many patients must pay out of pocket for AOMs. Table 3 provides estimated retail costs and possible price reductions with online discounts and coupons. Medicare beneficiaries are ineligible for manufacturer discounts. Financial considerations are important for patients’ ability to initiate and adhere to ongoing treatment. Medical practices may need to allocate staff time for prior authorizations commonly required to determine AOM coverage.
許多美國人缺乏對抗肥胖藥物（AOMs）的保險覆蓋。醫療保險不會僅僅因為治療肥胖而覆蓋 AOMs——它可能會覆蓋經 FDA 批准並用於肥胖合併其他疾病的 AOM（例如，semaglutide 最近被批准用於減少超重或肥胖及已有心血管疾病者的心血管風險）。醫療保險可能會覆蓋用於治療 2 型糖尿病的營養刺激激素類藥物。只有少數州的醫療補助計劃會覆蓋 AOMs。雇主贊助的健康保險通常也不包括 AOMs 的覆蓋。因此，許多患者必須自掏腰包支付 AOMs 的費用。表 3 提供了估計的零售成本以及在線折扣和優惠券可能帶來的價格減少。醫療保險受益者不符合製造商折扣的資格。財務考量對於患者啟動和堅持持續治療的能力至關重要。醫療機構可能需要分配員工時間以進行通常需要的事先授權，以確定 AOM 的覆蓋情況。

Limitations 限制

This review has several limitations. First, effects of AOMs on physical function and quality of life were not reviewed. Second, quality of included studies was not systematically evaluated. Third, some relevant articles may have been missed. Fourth, lisdexamfetamine, approved for binge eating disorder, and setmelanotide, approved for monogenetic and syndromic obesity, were not discussed.
這篇評論有幾個限制。首先，未對 AOMs 對身體功能和生活質量的影響進行評估。其次，納入研究的質量未進行系統性評估。第三，可能遺漏了一些相關文章。第四，未討論利司達帕胺（lisdexamfetamine），該藥物已獲批准用於暴食症，以及塞美那肽（setmelanotide），該藥物已獲批准用於單基因和綜合症性肥胖。

Conclusions 結論

Obesity is associated with multiple comorbidities. AOMs are effective adjunctive therapies to lifestyle changes for improved weight loss and health outcomes.
肥胖與多種共病有關。AOMs 是改善減重和健康結果的有效輔助療法，與生活方式改變相結合。

JAMA | Review Medications for Obesity A Review JAMA | 評論 肥胖藥物的回顧

Abstract 摘要

Methods 方法

Intragastrointestinal Medications腸胃內用藥物

Orlistat 奧利司他

Cellulose-Citric Acid Hydrogel纖維素-檸檬酸水凝膠

Centrally Acting Medications中樞作用藥物

Phentermine 芬特明

Phentermine-Topiramate 芬特明-托吡酯

Naltrexone-Bupropion 納曲酮-布普洛尼

Nutrient-Stimulated Hormone-Based Medications營養刺激激素基藥物

Liraglutide 利拉魯肽

Semaglutide

Tirzepatide

AOMs in Development 開發中的 AOMs

Lifestyle Change and AOMs生活方式改變與 AOMs

Safety of AOMs AOMs 的安全性

Duration of AOM UseAOM 使用的持續時間

Limitations 限制

Conclusions 結論

JAMA | Review
Medications for Obesity A Review
JAMA | 評論肥胖藥物的回顧

Intragastrointestinal Medications
腸胃內用藥物

Cellulose-Citric Acid Hydrogel
纖維素-檸檬酸水凝膠

Centrally Acting Medications
中樞作用藥物

Nutrient-Stimulated Hormone-Based Medications
營養刺激激素基藥物

Lifestyle Change and AOMs
生活方式改變與 AOMs

Duration of AOM Use
AOM 使用的持續時間