Phentermine-topiramate shows best chance of weight loss at 1 year




The combination weight-loss drug phentermine plus topiramate is associated with the highest odds of individuals being able to lose 5% of their body weight within 1 year, according to a meta-analysis comparing outcomes and adverse events for orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide.

Researchers analyzed 28 randomized placebo- or active-controlled clinical trials involving a total of 29,018 participants and found those who took phentermine-topiramate had a ninefold greater likelihood of achieving a 5% weight loss by 1 year than did those on placebo, according to a paper published in the June 14 issue of JAMA.

Liraglutide showed the second-highest odds of achieving a 5% weight loss at 1 year (odds ratio, 5.54), followed by naltrexone-bupropion (OR, 3.96), lorcaserin (OR, 3.10), and orlistat (OR, 2.70).

Nearly one-quarter of individuals on placebo achieved at least a 5% weight loss by 1 year, compared with three-quarters of individuals taking phentermine-topiramate, 63% of those taking liraglutide, 55% taking naltrexone-bupropion, 49% taking lorcaserin, and 44% taking orlistat (JAMA 2016;315:2424-34. doi: 10.1001/jama.2016.7602).

Of those on placebo, only 9% achieved at least a 10% weight loss at 1 year, compared with 54% of patients taking phentermine-topiramate, 34% of patients on liraglutide, 30% of patients on naltrexone-bupropion, 25% of those taking lorcaserin, and 20% of those taking orlistat.

Phentermine-topiramate was also associated with the greatest weight loss, compared with placebo, with patients losing a mean of 8.8 kg vs. 5.2 kg with liraglutide, 5 kg with naltrexone-bupropion, 3.2 kg with lorcaserin, and 2.6 kg with orlistat.

While all active drugs were associated with a higher rate of discontinuation because of adverse events than was seen with placebo, liraglutide was associated with the greatest risk of discontinuation, compared with placebo, followed by naltrexone-bupropion, phentermine-topiramate, orlistat, and then lorcaserin.

Dr. Rohan Khera of the department of internal medicine at the University of Iowa, Iowa City, and coauthors wrote that pharmacologic treatment decisions should consider coexisting medical conditions that might influence for or against a particular choice for weight loss.

“For example, liraglutide may be a more appropriate agent in people with diabetes because of its glucose-lowering effects,” they wrote. “Conversely, naltrexone-bupropion in patients with chronic opiate or alcohol dependence may be associated with neuropsychiatric complications.

“Ultimately, given the differences in safety, efficacy, and response to therapy, the ideal approach to weight loss should be highly individualized, identifying appropriate candidates for pharmacotherapy, behavioral interventions, and surgical interventions.”

Two study authors were supported by a grant from the National Library of Medicine or the National Institute of Diabetes and Digestive and Kidney Diseases. One author reported receiving funding, participating on advisory committees, and serving as a consultant with a range of pharmaceutical manufacturers, as well as being a cofounder of Liponexus. Another author reported research support from NovoNordisk for research on liraglutide. No other disclosures were reported.

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