AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity
Open accessAbstract
BACKGROUND & AIMS Pharmacological management of obesity improves outcomes and decreases the risk of obesity-related complications. This American Gastroenterological Association guideline is intended to support practitioners in decisions about pharmacological interventions for overweight and obesity. METHODS A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis of the following agents: semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate extended-release (ER), naltrexone-bupropion ER, orlistat, phentermine, diethylpropion, and Gelesis100 oral superabsorbent hydrogel. The guideline panel used the evidence-to-decision framework to develop recommendations for the pharmacological management of obesity and provided implementation considerations for clinical practice. RESULTS The guideline panel made 9 recommendations. The panel strongly recommended the use of pharmacotherapy in addition to lifestyle intervention in adults with overweight and obesity (body mass index ≥30 kg/m2, or ≥27 kg/m2 with weight-related complications) who have an inadequate response to lifestyle interventions. The panel suggested the use of semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate ER, and naltrexone-bupropion ER (based on moderate certainty evidence), and phentermine and diethylpropion (based on low certainty evidence), for long-term management of overweight and obesity. The guideline panel suggested against the use of orlistat. The panel identified the use of Gelesis100 oral superabsorbent hydrogel as a knowledge gap. CONCLUSIONS In adults with overweight and obesity who have an inadequate response to lifestyle interventions alone, long-term pharmacological therapy is recommended, with multiple effective and safe treatment options.
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Pharmacotherapy is indicated for a body mass index of at least 30 kg/m2 or at least 27 kg/m2 in the presence of comorbidities.
“Pharmacotherapy is indicated when body mass index (BMI) is !30kg/m 2 or !27 kg/m 2 in the presence of comorbidities (Apovian et al, 2015;Garvey et al, 2016;Grunvald et al, 2022).”
From Emerging pharmacotherapies for obesity: A systematic review (2025) · cites this paper as Grunvald et al, 2022
The Discussion gives the BMI thresholds of 30 kg/m², or 27 kg/m² with a weight-related complication, for an approved obesity medication. Recommendation 1 supports pharmacotherapy for adults with obesity or overweight with weight-related complications, but specifies an inadequate response to lifestyle interventions and recommends adding medication to those interventions. The claim omits that condition, making the thresholds sound sufficient on their own. (LLM, conf=0.86)
Experimental — accuracy not yet measuredEvidence-based obesity treatment includes interventions addressing 5 major categories: behavioral interventions, nutrition, physical activity, pharmacotherapy, and metabolic/bariatric procedures.
“Evidence-based obesity treatment includes interventions addressing 5 major categories: behavioral interventions, nutrition, physical activity, pharmacotherapy, and metabolic/bariatric procedures.”
From Obesity Management in Adults (2023) · cites this paper as [10]
The Summary of the Evidence identifies diet, physical activity, and behavior therapy as essential lifestyle interventions and evaluates pharmacotherapy alongside them. Limitations and Evidence Gaps mentions bariatric and metabolic interventions, but as treatments for which comparative evidence is needed; the guideline does not present these as five major categories of evidence-based treatment. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMean weight loss with orlistat is 2.8% to 4.8%, and gastrointestinal adverse effects are frequent, including flatulence, steatorrhea, and diarrhea.
“Mean weight loss with orlistat is 2.8% to 4.8%, and gastrointestinal adverse effects are frequent, including flatulence, steatorrhea, and diarrhea.10,109”
From Obesity Management in Adults (2023) · cites this paper as [10]
The Benefits section reports 2.78% total body weight loss versus placebo, supporting the lower end of the claimed range, but it does not report 4.8%. The Harms section reports increased discontinuation due to gastrointestinal effects and names flatulence and oily stools; it does not specifically name diarrhea. Page numbers were not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredFour sympathomimetic oral amines-phentermine, diethylpropion, benzphetamine, and phendimetrazine-are currently FDA approved for short-term use (12 weeks).
“Four sympathomimetic oral amines, phentermine, diethylpropion, benzphetamine, and phendimetrazine are currently FDA approved for short-term use (12 weeks).10,113,114”
From Obesity Management in Adults (2023) · cites this paper as [10]
The Implementation Considerations (page unavailable) state that phentermine and diethylpropion monotherapy are each FDA-approved for short-term use (12 weeks). The passages do not establish the same approval or duration for benzphetamine or phendimetrazine, so they support only two of the four drugs named. (LLM, conf=0.88)
Experimental — accuracy not yet measuredObesity is a relapsing, remitting chronic disease.
“In light of the burden obesity places on human health and a growing understanding of the physiologic processes underlying weight regulation, scientific organizations including the American Medical Association, the National Institutes of Health, and others now recognize it as a relapsing, remitting chronic disease.”
From Effectiveness and safety of drugs for obesity (2024) · cites this paper as [10]
The Study Selection, Data Collection, and Analysis section explicitly calls obesity a chronic disease, and Limitations and Evidence Gaps describes physiological defenses against sustained weight loss. Neither passage characterizes obesity as relapsing and remitting or says that the American Medical Association and National Institutes of Health recognize it in those terms. Page numbers were not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
In 2022, the American Gastroenterological Association published guidelines that are the first to make priority recommendations for antiobesity medication selection based on evidence from individual agent trials, explicitly recommending semaglutide 2.4 mg because of the magnitude of clinical benefit.
“Finally, in 2022, the American Gastroenterological Association published the most recent guidelines on the pharmacotherapy of obesity.10 These guidelines are the first to make priority recommendations for antiobesity medication selection on the basis of available evidence from individual agent trials, explicitly recommending the use of semaglutide 2.4 mg because of the magnitude of clinical benefi”
From Effectiveness and safety of drugs for obesity (2024) · cites this paper as [10]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe American Gastroenterological Association guidelines prioritize liraglutide 3.0 mg, followed by phentermine-topiramate, and then naltrexone-bupropion.
“The American Gastroenterological Association guidelines next prioritize liraglutide 3.0 mg, followed by phentermine-topiramate, and then naltrexone-bupropion.”
From Effectiveness and safety of drugs for obesity (2024) · cites this paper as [10]
The Conditional Moderate recommendations list liraglutide 3.0 mg, phentermine-topiramate ER, and naltrexone-bupropion ER in that order, each as an option alongside lifestyle modifications. But the Limitations and Evidence Gaps section says clinicians have limited guidance for hierarchical decision-making; the list order does not establish the claimed priority ranking. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe American Gastroenterological Association guidelines advise against the use of orlistat as an antiobesity medication.
“Importantly, they advise against the use of orlistat as an antiobesity medication, given the modern available options that are superior and better tolerated.”
From Effectiveness and safety of drugs for obesity (2024) · cites this paper as [10]
The guideline’s recommendation table suggests against orlistat for adults with obesity or overweight with weight-related complications, and the Discussion describes this as a conditional recommendation. The Discussion attributes that decision to modest weight loss and bothersome adverse effects; it does not say the recommendation was made because modern alternatives are both superior and better tolerated. It also notes that some patients may reasonably choose orlistat. (LLM, conf=0.86)
Experimental — accuracy not yet measuredClinicians can offer multiple effective obesity treatments.
“clinicians can offer multiple effective obesity treatments.9–11”
From Obesity Management in Adults (2023) · cites this paper as [10]
Clinical guidelines support long-term antiobesity medication use.
“clinical guidelines support long-term antiobesity medication use.4,10”
From Obesity Management in Adults (2023) · cites this paper as [10]
The newer American Gastroenterological Association (AGA) guidelines offer some guidance on the use of liraglutide and semaglutide.
“The newer American Gastroenterological Association (AGA) guidelines 49 offer some guidance on the use of liraglutide and semaglutide.”
Gelesis100 is a superabsorbent orally administered hydrogel capsule that releases cellulose and citric acid particles, thereby increasing bulk in the stomach and creating a sensation of satiety.
“It is a superabsorbent orally administered hydrogel capsule that releases cellulose and citric acid particles, thereby increasing bulk in the stomach and creating a sensation of satiety.10”
From Obesity Management in Adults (2023) · cites this paper as [10]
Orlistat may cause malabsorption of fat-soluble vitamins; patients should take a multivitamin containing vitamins A, D, E, and K 2 hours apart from orlistat daily.
“Orlistat may cause malabsorption of fat-soluble vitamins; thus, patients should take a multivitamin containing vitamins A, D, E, and K 2 hours apart from orlistat daily.10”
From Obesity Management in Adults (2023) · cites this paper as [10]
Recent American Gastroenterological Association guidelines conditionally recommended against orlistat use given its modest weight loss and gastrointestinal adverse effects.
“Recent American Gastroenterological Association guidelines conditionally recommended against orlistat use given its modest weight loss and gastrointestinal adverse effects.10”
From Obesity Management in Adults (2023) · cites this paper as [10]
The American Gastroenterological Association guidelines allow for off-label long-term phentermine prescribing, while acknowledging low quality of evidence.
“Like the Endocrine Society, the American Gastroenterological Association guidelines also allow for off-label long term phentermine prescribing, while acknowledging the low quality of evidence in this space.”
From Effectiveness and safety of drugs for obesity (2024) · cites this paper as [10]
Orlistat produces a placebo-subtracted weight loss of 2.8% (95% CI 2.4-3.2) up to 4 years.
“2.8% (95% CI 2.4-3.2) 10 placebo subtracted % weight loss up to 4 years”
From Effectiveness and safety of drugs for obesity (2024) · cites this paper as [10]
Naltrexone-bupropion SR produces a placebo-subtracted weight loss of 3.0% (95% CI 2.5-3.5) at 56 weeks.
“3.0% (95% CI 2.5-3.5) 10 Placebo subtracted % weight loss at 56 weeks”
From Effectiveness and safety of drugs for obesity (2024) · cites this paper as [10]
Lifestyle intervention can reduce side effects in patients taking GLP-1 receptor agonists.
“Lifestyle intervention can also reduce side effects in patients taking GLP-1 receptor agonists including recommending smaller (and if needed, more frequent) meals that are lower in fat [14,86].”
From Lifestyle Medicine for Obesity in the Era of Highly Effective Anti-Obesity Treatment (2025) · cites this paper as [14]
The Summary of the Evidence describes lifestyle interventions alongside GLP-1 receptor agonist treatment, but does not say they reduce side effects. The Implementation Considerations instead say gradual dose titration may mitigate nausea and vomiting; searches for smaller, more frequent, or lower-fat meals found no such advice for GLP-1 receptor agonists in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredControlled trials (with histological endpoints or liver-related outcomes) of weight-loss agents other than incretin hormone analogues have either not been performed or have been inconclusive.
“Controlled trials (with histological endpoints or liver-related outcomes) of weight-loss agents other than incretin hormone analogues 433 ( e.g. orlistat, phentermine-topiramate, naltrexone-bupropion) have either not been performed or have been inconclusive.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [433]
The Study Selection, Data Collection, and Analysis section lists weight-loss and safety outcomes, not liver histology or liver-related outcomes. The Benefits sections report weight-loss results for agents including orlistat and naltrexone-bupropion, but do not establish whether controlled trials with liver endpoints were absent or inconclusive. Searches for liver histology, NASH, and liver-related trial outcomes did not find a passage resolving that claim. (LLM, conf=0.73)
Experimental — accuracy not yet measuredPhentermine is frequently prescribed off-label for much longer than its short-term indication and has been by far the most prescribed anti-obesity medication in the US, primarily because of its low cost.
“Despite this short-term indication, phentermine is frequently prescribed off-label for much longer 20,22 and has been by far the most prescribed AOM in the US, 45,46 primarily because of its low cost.”
From Approach to Obesity Treatment in Primary Care: A Review (2024) · cites this paper as [20]
Not everyone with a BMI at or above these thresholds is an appropriate candidate for anti-obesity medications, and some individuals accrue risks at a lower BMI.
“However, not everyone with a BMI at or above these thresholds is an appropriate candidate for AOMs, and certain individuals accrue risks at a lower BMI.20”
From Approach to Obesity Treatment in Primary Care: A Review (2024) · cites this paper as [20]
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- Authors
- Grunvald, E., Shah, R., Hernaez, R., Chandar, A. K., Pickett-Blakely, O., Teigen, L. M., Harindhanavudhi, T., Sultan, S., Singh, S., & Davitkov, P.
- Affiliations
- University of California San Diego (US)
- Brigham and Women's Hospital (US)
- Case Western Reserve University (US)
- University of Minnesota (US)
- Louis Stokes Cleveland VA Medical Center (US)
- Corresponding author
- Grunvald, Eduardo
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2022-11
- Volume
- 163
- Issue
- 5
- Pages
- 1198-1225
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W4306870661
- Semantic Scholar
- 23c4214a9b92ebdb267bc80b077cfa61d1ae6e00
- Cited by
- 347
- References
- 160
- Citations by year
- 2026: 107 · 2025: 128 · 2024: 76 · 2023: 31 · 2022: 3
- FWCI
- 35.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Academy of Medicine
- Topics
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
- Keywords
- obesity, overweight, pharmacological weight loss, semaglutide, liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, phentermine, diethylpropion, superabsorbent hydrogels, obesity complications, lifestyle intervention, long-term weight management
- MeSH terms
- Liraglutide, Topiramate, Orlistat, Adult, Diethylpropion, Humans, Naltrexone, Obesity, Phentermine, Weight Loss, Bupropion, Anti-Obesity Agents, Hydrogels, Overweight
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