Phentermine-Topiramate May Be Best Medication for Weight Loss

By Lisa Rapaport

January 07, 2022

(Reuters Health) - Of all the available medications for treatment of overweight and obesity, phentermine-topiramate, followed by glucagon-like peptide 1 (GLP-1) receptor agonists, may be the most effective for weight loss, a systematic review and network meta-analysis of randomized controlled trials suggests.

Researchers examined data from 143 clinical trials, with a total of 49,801 participants, that assessed the proportion of patients who achieved at least a 5% weight reduction on different medications as compared with lifestyle interventions.

Every medication studied except levocarnitine was more effective than lifestyle interventions at helping patients achieve at least a 5% weight reduction, researchers report in The Lancet. When compared with lifestyle interventions, phentermine-topiramate was the most effective for meeting this weight loss benchmark (odds ratio 8.02), followed by glucagon-like peptide 1 (GLP-1) receptor agonists (OR 6.33).

"Clinicians and adults who might need weight-lowering drugs could discuss the benefits and harms and make a shared decision based on their values and preferences," said lead study author Dr. Sheyu Li, an associate professor of endocrinology and metabolism at Sichuan University in Chengdu, China.

"Phentermine-topiramate and GLP-1 receptor agonists showed the best weight-lowering effects, but it does not mean that most people should use it without considering their individualized context," Dr. Li said by email.

When researchers examined three GLP-1 receptor agonists separately, they found the largest likelihood of a weight reduction of 5% or more relative to lifestyle interventions with semaglutide (OR 9.82), followed by liraglutide (OR 4.91), and exenatide (OR 2.86).

Compared with lifestyle interventions, participants were also significantly more likely to experience at least a 10% weight loss with semaglutide (OR 13.32), followed by phentermine-topiramate (OR 9.74), and naltrexone-bupropion (OR 5.19).

Mean weight change from baseline was greatest with semaglutide (-11.41%), followed by phentermine-topiramate (-7.97%), liraglutide (-4.68%), and naltrexone-bupropion (-4.11%).

Odds of discontinuation due to adverse events were largest with naltrexone-bupropion (OR 2.69), liraglutide (OR 2.45), and phentermine-topiramate (OR 2.40).

The certainty of the evidence varied across studies and for the different medications included in the analysis. The highest level of certainty was for mean weight change from baseline and the odds of achieving a 5% or 10% weight reduction with phentermine-topiramate, GLP-1 receptor agonists as a class, and semaglutide.

One limitation of the study is the lack of individual patient data pooling, the authors note, and another is the wide variation in study population characteristics and duration of follow-up for weight loss endpoints.

Although the aim of the study was to assess the effectiveness of medication relative to lifestyle interventions, lifestyle interventions still have a key role in weight management, Dr. Li said.

"One should never recommend a weight-lowering drug before advising a sound and practical lifestyle modification strategy," Dr. Li said. "Meanwhile, for people with extremely severe obesity, bariatric surgery may be a life-saving choice that (has) more priority than medication."

SOURCE: The Lancet, online December 8, 2021.