The antidiabetic drug tirzepatide has been found to be safe and effective in weight management in patients with obesity in yet another trial.^1,2

Topline results of the multicenter phase 3 SURMOUNT-2 trial published last week as a press release show that tirzepatide (10 mg and 15 mg) achieved superior weight loss compared to placebo after 72 weeks of treatment.

SURMOUNT-2 is the second major trial to examine the efficacy and safety of tirzepatide (10 mg, 15 mg) as an adjunct to increased physical activity plus a low-calorie diet in 938 adults with obesity or overweight and type 2 diabetes from eight countries including India. The trial had two co-primary objectives, related to weight loss. Tirzepatide was found to meet both the primary end points.

The first primary endpoint was the efficacy of tirzepatide in causing mean percentage change in body weight from baseline at 72 weeks compared to placebo. Subcutaneous administration of 10 mg and 15 mg of tirzepatide resulted in weight loss of 13.4% (13.5 kg) and 15.7% (15.6 kg), respectively, when compared to weight loss of 3.3% (3.2 kg) in the placebo recipients. The second primary endpoint was the efficacy of tirzepatide in achieving ≥5% loss of body weight at 72 weeks compared to placebo. In the trial, 81.6% of subjects on tirzepatide 10 mg and 86.4% of those receiving the 15mg dose achieved at least 5% weight loss from baseline vs 30.5% of those taking placebo.

“For the treatment-regimen estimand (i.e., the estimated average treatment effect regardless of treatment discontinuation), results showed:

• Average body weight reductions: 12.8% (10 mg), 14.7% (15 mg), 3.2% (placebo)
• Percentage of participants achieving body weight reductions of ≥5%: 79.2% (10 mg), 82.7% (15 mg), 32.5% (placebo)
• Percentage of participants achieving body weight reductions of ≥15%: 39.7% (10 mg), 48.0% (15 mg), 2.7% (placebo)”

Tirzepatide was also safe. The side effects were mostly gastrointestinal in nature reported during the dose escalation period. These adverse effects were mild to moderate in intensity.

Tirzepatide is the first-in-class dual glucagon-like peptide-1 (GLP-1) agonist and glucose-dependent insulinotropic polypeptide (GIP) agonist and therefore has been dubbed a “twincretin”. It was approved in May 2022 for the treatment of type 2 diabetes in adults as adjunct to diet and exercise.

The SURPASS trials (1 to 5) published in 2021 established the robust efficacy of tirzepatide in achieving glycemic control and alongside also demonstrated additional weight loss benefits.

But the first trial to examine the efficacy of tirzepatide as treatment of obesity was the SURMOUNT-1 trial, which enrolled patients with overweight or obesity without diabetes. Published in NEJM in 2022, the average weight reduction with tirzepatide 10 mg was 19.5% and 20.9% with tirzepatide 15 mg vs 3.1% weight loss with placebo. 

Although the observed weight loss in SURMOUNT-2 was less than that in the SURMOUNT-1 trial, nevertheless these findings make a strong case for regulatory approval of tirzepatide as an anti-obesity medication.

The complete data of SURMOUNT-2 will be presented at the 83rd Scientific Sessions of the American Diabetes Association (ADA) to be held in San Diego in California in June. Results of SURMOUNT-3 and SURMOUNT-4 trials are expected later this year.

References

1. News release. Available at: https://investor.lilly.com/news-releases/news-release-details/lillys-tirzepatide-achieved-157-weight-loss-adults-obesity-or, April 27, 2023. Accessed on May 2, 2023.
2. Tirzepatide scores win in second obesity trial, SURMOUNT-2 - Medscape - Apr 27, 2023.