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

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 Los

• 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