Tirzepatide, marketed as Zepbound, has shown a significant reduction in the risk of type 2 diabetes in obese patients with prediabetes, according to a study published in the New England Journal of Medicine. The trial, a continuation of the SURMOUNT-1 trial, revealed that tirzepatide reduced the risk of diabetes by more than 90% over a three-year period compared to placebo.
The study, led by investigators at Weill Cornell Medicine, NewYork-Presbyterian, and Yale School of Medicine, followed 1,032 patients with obesity and prediabetes for 176 weeks. The results indicated that only 1.3% of patients treated with tirzepatide progressed to type 2 diabetes, compared to 13.3% of patients receiving a placebo.
Key Findings from the SURMOUNT-1 Trial Extension
The SURMOUNT-1 trial initially demonstrated that patients with obesity taking tirzepatide for 72 weeks experienced an average weight loss of 15% to 22.5%, depending on the dose. The extended study focused on the progression to type 2 diabetes in patients with prediabetes. After 176 weeks, over 90% of the patients on tirzepatide had normal A1c levels, compared to 59% of those on placebo.
"These results show that type 2 diabetes may be prevented, even in people who are on the verge of it, by using a medicine that causes weight loss," said Dr. Louis Aronne, study co-author and director of the Comprehensive Weight Control Center at Weill Cornell Medicine.
Mechanism of Action and Clinical Implications
Tirzepatide is a dual GIP and GLP-1 receptor agonist. It works by simulating nutrient-stimulated hormones, promoting weight loss and improving blood sugar control. The drug activates glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptors in the brain, pancreas, and other areas, leading to increased satiety, reduced food cravings, and enhanced insulin secretion.
The trial reported no new safety concerns, with common gastrointestinal side effects like nausea and vomiting decreasing over time, suggesting good tolerability for long-term use. However, a follow-up analysis after stopping treatment showed modest gains in weight and A1c levels, highlighting the potential need for chronic therapy.
Future Directions and Potential for Prediabetes Treatment
The study results suggest that tirzepatide could become the first approved treatment for prediabetes. Dr. Aronne noted the potential impact of such weight-loss drugs in preventing diabetes and related complications such as heart disease, liver and kidney disease, sleep apnea, and arthritis.
"Think about the impact these types of weight-loss drugs can have in preventing not only diabetes but also many other common diabetes-related complications such as heart disease, liver and kidney disease, sleep apnea, arthritis and more," he said.
Eli Lilly, the manufacturer of tirzepatide, has released detailed results from the SURMOUNT-1 phase 3 trial, where over 1,000 obese or overweight prediabetic participants were followed over the course of 176 weeks, making it the longest study to date of tirzepatide.
