AT DDW 2016

SAN DIEGO (FRONTLINE MEDICAL NEWS) – Phentermine-topiramate was the most effective long-term weight loss drug, based on findings from a network meta-analysis from the University of California, San Diego.

The investigators pooled data from 28 studies of phentermine-topiramate (Qsymia) and four other drugs: orlistat (Xenical, Alli), lorcaserin (Belviq), naltrexone-bupropion (Contrave), and liraglutide (Victoza, Saxenda). The most commonly prescribed weight loss drug in the United States – generic phentermine – was not included because it’s not indicated for long-term use.

“It’s good to have a problem of plenty,” said Dr. Siddharth Singh, but it also makes it hard to figure out which drug to prescribe, especially given the lack of head-to-head studies. He said he hopes the results will help. However, the 30%-45% attrition rate across the studies means that the results have to be interpreted cautiously, said Dr. Singh, who is in the division of gastroenterology in the department of internal medicine, UCSD.

Most of the studies were company-funded phase III trials of weight loss drugs vs. placebo; the trials all were at least 1 year long and included more than 29,000 overweight or obese adults. The analysis was limited to patients on the maximum recommended dose of each drug.

All the drugs were more effective than placebo, but phentermine-topiramate was the most effective, with about 75% of patients losing at least 5% of their weight at 1 year and more than half losing at least 10%, with an average weight loss above placebo of 9 kg. Phentermine-topiramate patients were 10 times more likely than patients on placebo to hit the 5% mark at 1 year; liraglutide patients were 5.5 times more likely to do so; naltrexone-bupropion patients were 4 times more likely; lorcaserin patients, 3.1 times more likely; and orlistat patients, 2.7 times more likely to hit the 5% mark. The spread was similar for weight loss of 10% or more at 1 year vs. placebo.

Phentermine-topiramate’s tolerability profile was acceptable, with 10% of patients quitting the drug by 1 year because of adverse events. The best tolerated was lorcaserin, with a discontinuation rate of 6%, and the least tolerated was liraglutide, with a 13% discontinuation rate. Patients were more likely to quit active drug than placebo in all the studies.

Of course, there are other considerations, especially comorbidities; liraglutide might be the best choice in diabetics, for instance, and patients with psychiatric issues might want to avoid naltrexone-bupropion and lorcaserin, Dr. Singh said.

Subjects were a median of 46 years old, and 74% were women. The median body mass index was 36 kg/m2. All the patients had lifestyle and nutrition counseling along with their study medications.

The investigators next plan to compare the drugs’ safety and efficacy in real world settings.

There was no industry funding for the work, and Dr. Singh had no relevant financial disclosures.