AGA Releases Updated Guidelines on Pharmacological Management of Adult Obesity

An obese patient speaking with a physician
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The American Gastroenterological Association developed 9 recommendations for pharmacological and lifestyle interventions for adults with obesity.

The American Gastroenterological Association (AGA) recommends long-term pharmacological therapy in adults with overweight and obesity when lifestyle interventions are inadequate. The updated clinical practice guidelines were published in Gastroenterology.

Guideline authors, who included a multidisciplinary panel of content experts and guideline methodologists, used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to develop 9 recommendations. The panel based these recommendations on best available supporting evidence from the literature regarding use of semaglutide (2.4 mg), liraglutide (3.0 mg), phentermine-topiramate extended-release (ER), naltrexone-bupropion ER, orlistat, phentermine, diethylpropion, and Gelesis100 oral superabsorbent hydrogel in the management of adult obesity.

Recommendation #1: The AGA strongly recommends adding pharmacological agents to lifestyle interventions over continuing lifestyle interventions alone if adults with obesity or overweight with weight-related complications demonstrate an inadequate response to lifestyle interventions.

Adults who demonstrate poor or inadequate responses to lifestyle interventions may benefit from the addition of adult obesity medications to their lifestyle regimen. Clinicians should select the most appropriate medication based on the patient’s clinical profile and needs, including but not limited to comorbid conditions, patient preferences, cost of the treatment, and patient access to the therapy.

As obesity is both a disease and a risk factor for other chronic illnesses, it is paramount to continue to assess the effect of weight loss using pharmacological interventions on important outcomes…

Recommendation #2: The AGA conditionally suggests using semaglutide 2.4 mg with lifestyle modifications, compared with lifestyle modifications alone, to treat adults with obesity or overweight with weight-related complications.

Semaglutide treatment should be considered a first-line treatment for most adults with obesity based on the magnitude of benefits reported in the literature.

According to evidence in the literature, semaglutide 2.4 mg demonstrated glucoregulatory benefits and was approved for the treatment of type 2 diabetes.

Possible adverse effects due to semaglutide treatment include:

  • nausea and vomiting due to delayed gastric emptying
  • increased risk for gallbladder disease
  • increased risk for pancreatitis

Recommendation #3: The AGA conditionally suggests using liraglutide 3.0 mg with lifestyle modifications, compared with lifestyle modifications alone, to treat adults with obesity or overweight with weight-related complications.

Similar to semaglutide, liraglutide 3.0 mg demonstrated glucoregulatory effects and is approved to treat type 2 diabetes.

Liraglutide may also result in delayed gastric emptying, leading to nausea and vomiting, and is associated with increased risk for pancreatitis and gallbladder disease.

Recommendation #4: The AGA conditionally suggests using phentermine-topiramate ER with lifestyle modifications, compared with lifestyle modifications alone, to treat adults with obesity or overweight with weight-related complications.

The panel recommended the preferential use of phentermine-topiramate ER in patients with comorbid obesity and migraine headaches because topiramate is also approved for the treatment of migraines.

Phentermine-topiramate ER is contraindicated in patients with a history of cardiovascular disease and uncontrolled hypertension as well as pregnant women or women of childbearing age without use of appropriate contraception.

During treatment with phentermine-topiramate ER, clinicians should monitor blood pressure and heart rate periodically.

Recommendation #5: The AGA conditionally suggests using naltrexone-bupropion ER with lifestyle modifications, compared with lifestyle modifications alone, to treat adults with obesity or overweight with weight-related complications.

The panel recommended preferential use of naltrexone-bupropion ER in patients with overweight or obesity with comorbid depression or patients who are attempting to stop smoking.

Naltrexone-bupropion ER is contraindicated in patients with seizure disorders or those taking opioids. It should be used with caution in those at risk for seizures.

During treatment with naltrexone-bupropion ER, clinicians should monitor blood pressure and heart rate periodically, particularly during the initial 12 weeks of treatment.

Recommendation #6: The AGA conditionally recommends against the use of orlistat to treat adults with obesity or overweight with weight-related complications due to gastrointestinal adverse effects.

The panel reasons that orlistat could be used in patients who value potential small weight loss benefits over the adverse gastrointestinal side effects caused by the medication. This recommendation is based on the meta-analysis from 12 randomized controlled trials, which indicated that most treatment discontinuations were due to adverse gastrointestinal effects. Analysis showed that the risk for these side effects was significantly higher in the orlistat groups compared with control groups.

Given that adverse effects primarily impacted the gastrointestinal tract, patients with a history of chronic malabsorption, chronic diarrhea, celiac disease, inflammatory bowel disease, or those who have undergone bariatric surgery may not be ideal candidates for treatment with orlistat.

Patients who decide to proceed with orlistat treatment should take a daily multivitamin that contains fat-soluble vitamins A, D, E, and K, which should be consumed at least 2 hours apart from orlistat.

Weight loss treatment with orlistat slightly increases risk for cholelithiasis.

Recommendation #7: The AGA conditionally suggests using phentermine with lifestyle modifications, compared with lifestyle modifications alone, to treat adults with obesity or overweight with weight-related complications.

Phentermine monotherapy is approved by the United States Food and Drug Administration (FDA) only for short-term use within 12 weeks. In contrast, due to the chronic nature of obesity and overweight, clinicians may opt for the off-label application of phentermine.

Similar to phentermine-topiramate ER, phentermine is contraindicated in patients with a history of cardiovascular disease.

Clinicians should periodically check blood pressure and heart rate during treatment with phentermine.

Recommendation #8: The AGA conditionally suggests using diethylpropion with lifestyle modifications, compared with lifestyle modifications alone, to treat adults with obesity or overweight with weight-related complications.

Similar to phentermine, diethylpropion is FDA-approved only for short-term use within 12 weeks. As such, clinicians may use diethylpropion monotherapy in an off-label fashion to treat the chronic conditions of overweight or obesity.

Diethylpropion is contraindicated in patients with a history of cardiovascular disease.

Clinicians should periodically check blood pressure and heart rate during treatment with diethylpropion.

Recommendation #9: The AGA contingently recommends using Gelesis100 oral superabsorbent hydrogel only in the context of a clinical trial in adults with BMI between 25 and 40 kg/m2 secondary to a knowledge gap for this intervention.

Only one randomized controlled trial provided evidence for Gelesis100 oral superabsorbent hydrogel with no indicated harms of treatment. The panel reported that this study provided low quality evidence in support of the intervention due to serious imprecisions due to low event rates that measured both harms and benefits of the treatment.

“As obesity is both a disease and a risk factor for other chronic illnesses, it is paramount to continue to assess the effect of weight loss using pharmacological interventions on important outcomes, such as cardiovascular events, nonalcoholic fatty liver disease, mortality, and cancer incidence and treatment response, among others,” the guideline authors noted.

References:

Grunvald E, Shah R, Hernaez R, et al. AGA clinical practice guideline on pharmacological interventions for adults with obesity. Gastroenterology. 2022;163(5):1198-1225. doi:10.1053/j.gastro.2022.08.045