4 anti-obesity meds: AGA top picks

Obese adults with weight-related complications who do not respond adequately to lifestyle interventions should be offered one of four anti-obesity medications, according to the new clinical practice guideline on pharmacological interventions released by the American Gastroenterological Association (AGA).

Obesity is an excessive fat accumulation that could impair health. If lifestyle interventions alone are insufficient to lose weight, the AGA recommends adding semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate extended-release (ER), and naltrexone-buproprion ER, based on moderate-certainty evidence. [Gastroenterology 2022;163:1198-1225]

All four anti-obesity drugs are approved for long-term use – with evidence of moderate- to large-magnitude weight loss, yet small or nonsubstantial harm – cementing its position in the new guideline.

Generally, anti-obesity medications need to be used for chronic adjunctive management of obesity, said guideline authors led by Dr Eduardo Grunvald from the University of California San Diego in La Jolla, California, US.  “The decision about which drug to use should be based on the clinical profile and needs of the patient, comorbidities, preference, cost, and access to therapy.”

Also recommended in the guideline, based on lower certainty evidence, are phentermine and diethylpropion.

Orlistat, a lipase inhibitor, is however not advised. “However, for patients who place a high value on the potential small weight loss benefit and low value on gastrointestinal side effects, they may reasonably choose treatment with orlistat. These patients should take a multivitamin that contains vitamins A, D, E, and K daily, at least 2 hours apart from orlistat though.”

The use of nonsystemic superabsorbent hydrogel Gelesis100 is not recommended, except in the context of a clinical trial.

The guideline is targeted at gastroenterologists, primary care clinicians, endocrinologists, and providers caring for overweight and obese patients.

Semaglutide and liraglutide

Both semaglutide and liraglutide have glucoregulatory benefits and are approved for the treatment of type 2 diabetes. But given the magnitude of net benefit,  semaglutide may be prioritized over other approved anti-obesity medications for the long-term treatment of obesity in most patients,  said the authors.

Phentermine-topiramate ER

In obese patients with comorbid migraines, the combination of phentermine and topiramate ER may be preferred. However, it should be avoided in those with a history of cardiovascular disease and uncontrolled hypertension. Blood pressure (BP) and heart rate should be monitored periodically in those taking the combination regimen.

Phentermine, a noradrenergic sympathomimetic amine, is US FDA-approved as monotherapy for short-term use (12 weeks) in the obese.

Naltrexone-bupropion ER

For overweight or obese patients trying to quit smoking and those with depression, a fixed-dose combination of naltrexone-bupropion ER may be considered. The drug should however be avoided in patients with seizure disorders. Caution is likewise advised in patients at risk of seizures.

The authors said naltrexone-bupropion ER should not be used concomitantly with opiates. Importantly, clinicians are advised to monitor BP and heart rate in patients taking the two-drug combination, particularly in the first 12 weeks of treatment.

Many are failing lifestyle interventions

The substantial increase in obesity worldwide has contributed to a dramatic increase in the risk of debilitating obesity-related complications, including cardiovascular disease, stroke, type 2 diabetes, nonalcoholic steatohepatitis, obstructive sleep apnoea, osteoarthritis, and colorectal cancer, that in turn diminish both life expectancy and quality of life.

Lifestyle intervention is the cornerstone of obesity management. However, it is rarely enough for long-term maintenance of weight loss.

Despite the availability of highly effective pharmacological therapies for obesity, these agents are not widely used in practice.

Basis for informed decisions

The guideline, developed by a panel of 10 experts and one patient representative, is not intended to impose a standard of care, rather it provides the basis for rational, informed decisions for healthcare professionals managing overweight or obese patients.

“No recommendation can include all the unique individual circumstances that must be considered when making recommendations for individual patients,” they said. “However, discussions around benefits and harms can be used for shared decision-making.”

The guideline was based on a systematic review and meta-analysis of randomized controlled trials of FDA-approved anti-obesity medications through January 1, 2022.

Obesity is considered by many as a lifestyle issue, but the American Medical Association acknowledged it as a chronic disease that should be treated as far back as 2013.