Phentermine-topiramate most effective drug for weight loss, meta-analysis finds

Among glucagon-like peptide-1 receptor agonists, semaglutide appeared to be the most effective for weight loss, with a higher likelihood of weight loss of 5% or more and percentage body weight change and a similar risk of adverse events.

Phentermine-topiramate and glucagon-like peptide-1 (GLP-1) receptor agonists appeared to be the most effective drugs for weight loss in adults with overweight and obesity, a meta-analysis found.

Researchers reviewed 143 eligible trials including 49,810 participants for their systematic review and meta-analysis. The patients' median baseline body mass index was 35.3 kg/m2, and median length of follow-up was 24 weeks. Results were published Dec. 8 by The Lancet.

Except for levocarnitine, all of the studied drugs lowered body weight compared with lifestyle modification alone. According to high- to moderate-certainty evidence, phentermine-topiramate was the most effective for decreasing weight compared to lifestyle modification (odds ratio [OR] of ≥5% weight reduction, 8.02 [95% CI, 5.24 to 12.27]; mean difference [MD] of percentage body weight change, −7.97 [95% CI, −9.28 to −6.66]) followed by GLP-1 receptor agonists (OR, 6.33 [95% CI, 5.00 to 8.00]; MD, −5.76 [95% CI, −6.30 to −5.21]).

Among GLP-1 receptor agonists, semaglutide appeared most effective, performing better than liraglutide and exenatide, the study authors wrote. Semaglutide showed substantially larger benefits than other drugs in its class for both likelihood of weight loss of 5% or more (OR, 9.82; 95% CI, 7.09 to 13.61) and percentage body weight change (MD, −11.41; 95% CI −12.54 to −10.27) with a similar risk of adverse events. Naltrexone-bupropion (OR, 2.69; 95% CI, 2.11 to 3.43), phentermine-topiramate (OR, 2.40; 95% CI, 1.69 to 3.42), GLP-1 receptor agonists (OR, 2.17; 95% CI, 1.71 to 2.77), and orlistat (OR, 1.72; 95% CI, 1.44 to 2.05) were associated with increased adverse events that led to discontinuation of therapy.

These findings should aid evidence-based decision making for patients and clinicians, the study authors noted. “The moderate or high certainty evidence for most comparisons mandates the confident application of these findings as guides for clinical practice,” they wrote.