How did diabetes drugs become weight-loss drugs, and what did the trials find?

They started as diabetes drugs. GLP-1 receptor agonists were originally developed to treat type 2 diabetes, and people with diabetes who were treated with them often lost weight, unlike with other diabetes treatments that commonly cause weight gain. Later, some of these medicines were tested and approved for obesity itself. The dates tell the story: liraglutide was approved in the European Union in 2009 and in the United States in 2010, Ozempic in the US in December 2017, Wegovy for long-term weight management in June 2021, tirzepatide for type 2 diabetes in May 2022, and for weight loss in November 2023.

What did the weight-loss trials find? In STEP 1, which was funded by Novo Nordisk, 1,961 adults with obesity, or overweight plus a weight-related condition, and no diabetes were randomly assigned to 68 weeks of weekly semaglutide or placebo, plus lifestyle intervention. On average body weight changed by -14.9% with semaglutide against -2.4% with placebo. In SURMOUNT-1, supported by Eli Lilly, adults on weekly tirzepatide for 72 weeks changed by -15.0%, -19.5% or -20.9% from the lowest to the highest dose group, against -3.1% with placebo.

Those are averages across groups of people, from company-funded trials, not predictions for any one person. A 2022 review found these drugs more promising than earlier weight-loss drugs, though less effective than bariatric surgery. In a 72-week open-label head-to-head trial, tirzepatide at the maximum tolerated dose produced greater mean weight loss than semaglutide.

The contrast with the past is sharp. Fen-phen, a pair of weight-loss drugs, had more than 18 million US prescriptions in 1996 and was withdrawn in September 1997 after evidence that it could cause valvular heart disease.