Tirzepatide Demonstrates Long-Term Weight Reduction and Diabetes Risk Reduction in Obesity and Prediabetes: NEJM

A three-year study published in the New England Journal of Medicine revealed striking results for individuals with obesity and prediabetes who were treated with tirzepatide. The researchers found that tirzepatide in this population led to significant and sustained weight loss, as well as a notably reduced risk of progressing to type 2 diabetes compared to those receiving a placebo.

Obesity is a chronic condition and a key risk factor for a range of other health issues, including type 2 diabetes. In a previous analysis of the SURMOUNT-1 trial, tirzepatide produced significant and sustained weight loss in individuals with obesity over a 72-weeks. In the study, Ania M. Jastreboff, Yale School of Medicine, New Haven, CT, and colleagues present three-year safety outcomes for tirzepatide, along with its effectiveness in reducing weight and preventing the progression to type 2 diabetes in individuals with both obesity and prediabetes.

For this purpose, the researchers conducted a phase 3, double-blind, randomized, controlled trial involving 2,539 participants with obesity, including 1,032 who also had prediabetes. Participants were randomly assigned in a 1:1:1:1 ratio to receive once-weekly doses of tirzepatide at 5 mg, 10 mg, or 15 mg, or a placebo. The analysis focused on those with both obesity and prediabetes, who received their assigned treatment for a total of 176 weeks, followed by a 17-week off-treatment period.

The study's primary objectives were three key secondary endpoints, controlled for type I error: the percent change in body weight from baseline to week 176 and the onset of type 2 diabetes during the 176-week and 193-week periods.

The key findings of the study at 176 weeks are as follows:

• Weight Loss
  • Participants receiving tirzepatide showed significant weight reduction compared to the placebo group:
    • 5 mg dose: −12.3% mean percent change in body weight.
    • 10 mg dose: −18.7% mean percent change in body weight.
    • 15 mg dose: −19.7% mean percent change in body weight.
    • Placebo group: −1.3% mean percent change in body weight.
• Type 2 Diabetes Diagnosis:
  • Fewer participants in the tirzepatide groups were diagnosed with type 2 diabetes compared to the placebo group:
    • Tirzepatide group: 2.4% developed type 2 diabetes.
    • Placebo group: 13.7% developed type 2 diabetes (hazard ratio, 0.12).
• Adverse Events
  • The most common adverse events were gastrointestinal issues, primarily during the dose-escalation phase in the first 20 weeks of the trial. These were mostly mild to moderate in severity.
  • There were no new safety signals during the study besides those related to coronavirus disease 2019 (COVID-19).

"As tirzepatide becomes more widely available, it offers a promising option for those struggling with obesity and prediabetes, providing a new pathway for preventing the onset of type 2 diabetes and improving overall metabolic health. The ongoing success of tirzepatide in clinical settings signals a bright future for treating these interconnected health issues," the researchers concluded.

Reference:

DOI: 10.1056/NEJMoa2410819