Summary:
Addressing obesity as a chronic condition, the SURMOUNT-4 trial explored the efficacy of tirzepatide, a medication combining GIP and GLP-1 receptor agonism, in maintaining weight loss. The trial involved a 36-week open-label tirzepatide lead-in treatment period followed by a 52-week double-blind, placebo-controlled phase. The study revealed significant weight maintenance and additional reduction in participants continuing tirzepatide compared to those switched to placebo. Tirzepatide demonstrated consistent improvements in cardiometabolic parameters and patient-reported outcomes, with an acceptable safety profile.
The Study:
Obesity, considered a persistent, progressive ailment, poses challenges in maintaining weight reduction achieved through lifestyle interventions alone. Thus, guidelines recommend adjunctive antiobesity medications. Tirzepatide, a single molecule merging GIP and GLP-1 receptor agonism, has shown promising effects on appetite, food intake, and metabolism.
The SURMOUNT-4 trial aimed to investigate the impact of sustained treatment with the maximum tolerated dose of tirzepatide versus placebo on maintaining weight reduction following an initial open-label treatment period in individuals with obesity or overweight.
Methods: The trial involved a phase 3 randomized withdrawal study conducted at multiple sites across several countries. Participants underwent an open-label lead-in period receiving tirzepatide, followed by randomization to either continue tirzepatide or switch to placebo for 52 weeks. Lifestyle counseling, adhering to a calorie-deficit diet and regular physical activity, was provided throughout the study.
Outcomes:
Primary endpoint analysis revealed a significant difference in weight change from week 36 to week 88 between tirzepatide and placebo groups. Participants on tirzepatide maintained substantial weight loss compared to those on placebo. Secondary endpoints demonstrated that tirzepatide-treated participants showed superior weight maintenance, reduced risk of regaining weight, and further reductions in body weight and waist circumference compared to the placebo group.
Moreover, tirzepatide resulted in significant improvements in various cardiometabolic risk factors and patient-reported outcomes throughout the study duration. Adverse events were predominantly gastrointestinal and generally mild to moderate in severity, with low rates of treatment discontinuation due to adverse events.
Conclusion:
Continued treatment with tirzepatide for 52 weeks post initial weight loss led to superior weight maintenance and additional reduction compared to placebo in individuals with obesity or overweight. Tirzepatide demonstrated consistent improvements in metabolic parameters and quality of life, reinforcing its potential as an effective option for managing obesity.
Citation:
Aronne LJ, Sattar N, Horn DB, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. Published online December 11, 2023. doi:10.1001/jama.2023.24945