A groundbreaking study published in the New England Journal of Medicine highlights the remarkable potential of tirzepatide in reducing type 2 diabetes risk and promoting substantial weight loss in individuals with obesity and prediabetes. The findings are based on a three-year phase 3 randomized controlled trial led by Jastreboff and colleagues, demonstrating the dual benefits of tirzepatide as a therapy for obesity management and diabetes prevention.
The double-blinded trial included 2,539 participants with obesity, of whom 1,032 also had prediabetes. Participants were randomly assigned to receive once-weekly injections of tirzepatide at doses of 5 mg, 10 mg, or 15 mg, or a placebo. After 176 weeks, the results showed that only 1.3% of tirzepatide-treated participants developed type 2 diabetes compared to 13.3% of those in the placebo group. Even after a 17-week off-treatment period, the protective effect of the drug persisted, with 2.4% of participants progressing to diabetes, compared to 13.7% in the placebo group. This translates to a hazard ratio of 0.07 during the treatment phase and 0.12 post-treatment, reflecting the drug’s long-lasting impact in reducing diabetes risk.
Tirzepatide acts by activating glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptors. This mechanism promotes satiety, reduces food intake, and enhances insulin secretion, collectively improving blood sugar control and facilitating significant weight loss. Over the treatment period, participants receiving tirzepatide achieved average weight reductions of 12.3%, 18.7%, and 19.7% for the 5 mg, 10 mg, and 15 mg doses, respectively. In contrast, the placebo group showed a modest weight loss of 1.3%.
These findings align with earlier results from the SURMOUNT-1 trial, which demonstrated that tirzepatide treatment over 72 weeks led to weight loss ranging from 15% to 22.5%, along with significant reductions in glycated hemoglobin (A1c) levels, a key indicator of blood sugar control. Extending these benefits, the current study showed that more than 90% of tirzepatide-treated participants achieved normal A1c levels after 176 weeks, compared to 59% in the placebo group.
In line with these outcomes, Hankosky et al. concluded that tirzepatide significantly reduced the 10-year predicted risk of developing type 2 diabetes in individuals with obesity or overweight, irrespective of their baseline glycemic status. This underscores the broad efficacy of the drug in reducing diabetes risk, even in those without prediabetes.
Safety data from the trial confirmed tirzepatide’s tolerability. The most common side effects were mild-to-moderate gastrointestinal symptoms, such as nausea and vomiting, primarily during the first 20 weeks of dose escalation. No new safety concerns were identified during the study.
These findings emphasize the transformative potential of tirzepatide to manage obesity, prevent diabetes, and possibly treat prediabetes. By addressing obesity, a primary risk factor for type 2 diabetes as a modifiable condition, tirzepatide offers new hope for millions of individuals at high risk of diabetes. With its long-term benefits and tolerable safety profile, tirzepatide could soon emerge as a cornerstone therapy in combating the global obesity and diabetes epidemic.
References
- Jastreboff AM, Roux CW le, Stefanski A, Aronne LJ, Halpern B, Wharton S, et al. Tirzepatide for Obesity Treatment and Diabetes Prevention. New England Journal of Medicine [Internet]. [cited 2024 Nov 27];0(0). Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2410819
- Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022 Jul 20;387(3):205–16.
- Hankosky ER, Wang H, Neff LM, Kan H, Wang F, Ahmad NN, et al. Tirzepatide reduces the predicted risk of developing type 2 diabetes in people with obesity or overweight: Post hoc analysis of the SURMOUNT-1 trial. Diabetes Obes Metab. 2023 Dec;25(12):3748–56.