With the publication of two recent Zepbound (tirzepatide) studies, GLP weight-loss drugs continue their streak of positive trials in obesity-related conditions. In the first study, Zepbound was compared to placebo in 731 patients with heart failure with preserved ejection fraction (HFpEF). After two years of follow-up, the absolute risk of a composite of death from cardiovascular causes or worsening heart failure was 5.4% lower in the Zepbound group (9.9% vs 15.3%). [Pubmed abstract] The second trial (N=1032), a substudy of the SURMOUNT-1 weight-loss trial, found that over 3.4 years, Zepbound significantly reduced the incidence of diabetes compared to placebo in individuals with prediabetes (1.3% vs 13.3%). [Pubmed abstract] These studies add to a growing list of trials, summarized below, where Zepbound and Wegovy (semaglutide) have been found to improve outcomes in obesity-related conditions.

• Obstructive sleep apnea (OSA): In a 52-week trial enrolling overweight adults with OSA (N=469), Zepbound significantly reduced the apnea-hypopnea index, body weight, hypoxic burden, and systolic blood pressure compared to placebo. [Pubmed abstract] In December 2024, Zepbound received FDA approval for moderate to severe OSA in adults with obesity.
• Nonalcoholic steatohepatitis (NASH): In a 52-week study (N=190) enrolling adults with NASH, more patients treated with Zepbound had NASH resolution compared to placebo (62% [15 mg dose] vs 10%) [Pubmed abstract]
• Heart failure with preserved ejection fraction (HFpEF): Like Zepbound, Wegovy has also been shown to improve HFpEF. In a 52-week study (N=529) enrolling obese adults with HFpEF, Wegovy was superior to placebo for improving heart failure symptoms and physical endurance. [Pubmed abstract]
• Secondary prevention of cardiovascular disease (CVD): In a 40-month study (N=17,604) enrolling overweight adults with a history of CVD, Wegovy was superior to placebo for reducing a composite of CVD events (6.5% vs 8%). [Pubmed abstract] Based on this study, Wegovy received FDA approval for the secondary prevention of CVD events.
• Knee osteoarthritis (OA): In a 68-week study (N=407) enrolling obese adults with moderate knee OA, Wegovy was superior to placebo for improving knee pain. [Pubmed abstract]
• Prediabetes: As discussed above, Zepbound was significantly better than placebo at preventing progression to diabetes over 3.4 years in participants with prediabetes (1.3% vs 13.3%). [Pubmed abstract]

To date, the FDA has granted two non-obesity indications for Zepbound and Wegovy: OSA for Zepbound and secondary prevention of CVD events for Wegovy. However, more are sure to come as these highly effective weight-loss drugs continue to change people's lives.