Tirzepatide new treatment option for people who are overweight or have obesity: SURMOUNT-1 clinical trial

In the 72-week, phase III SURMOUNT-1 clinical trial the researchers have reported that combination GIP and GLP-1 receptor agonist tirzepatide (Mounjaro) could soon be the next new treatment option for people who are overweight or have obesity.

SURMOUNT-1 trial has provided data to clinicians with an overview of the degree of weight loss achieved with use of tirzepatide versus placebo therapy in patients with obesity which was presented at the American Diabetes Association (ADA) 82nd Scientific Sessions.

The results of the study indicate 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight, with a mean percentage change of -15% at week 72 and up to 22.5% with the 15 mg dose.

For the efficacy estimandii, participants taking tirzepatide achieved average weight reductions of 16.0% (35 lb. or 16 kg on 5 mg), 21.4% (49 lb. or 22 kg on 10 mg) and 22.5% (52 lb. or 24 kg on 15 mg), compared to placebo (2.4%, 5 lb. or 2 kg). Additionally, 89% (5 mg) and 96% (10 mg and 15 mg) of people taking tirzepatide achieved at least 5% body weight reductions compared to 28% of those taking placebo.

All three doses of tirzepatide achieved all key secondary endpoints at 72 weeks of treatment for the efficacy estimand, including:

1. Percentage of participants achieving at least 10% body weight reductions: 73% (5 mg, not controlled for type 1 error), 86% (10 mg) and 90% (15 mg) compared to 14% with placebo.

2. Percentage of participants achieving at least 15% body weight reductions: 50% (5 mg, not controlled for type 1 error), 74% (10 mg) and 78% (15 mg) compared to 6.0% with placebo.

3. Percentage of participants achieving at least 20% body weight reductions: 32% (5 mg, not controlled for type 1 error), 55% (10 mg) and 63% (15 mg) compared to 1.3% with placebo.

4. Change in waist circumference from baseline: -14.6 cm (5 mg, not controlled for type 1 error), ‑19.4 cm (10 mg) and -19.9 cm (15 mg) compared to -3.4 cm with placebo.

All three doses of tirzepatide achieved an additional secondary endpoint at 72 weeks of treatment, measuring the percentage of participants achieving at least 25% body weight reductions (not controlled for type 1 error): 16.5% (5 mg), 35% (10 mg) and 39.7% (15 mg) compared to 0.3% with placebo.

Participants taking tirzepatide also achieved an approximately three times greater percent reduction in fat mass versus lean mass (33.9% fat mass reduction compared to a 10.9% lean mass reduction).

"Obesity is a chronic, treatable disease, and individuals living with obesity deserve effective and safe treatment options that can help restore their weight to levels that support optimal health," said Ania Jastreboff, MD, Ph.D., Associate Professor of Medicine & Pediatrics, Endocrinology & Metabolism, at Yale School of Medicine; Director, Weight Management & Obesity Prevention at the Yale Stress Center; and co-Director of the Yale Center for Weight Management. "In SURMOUNT-1, participants taking tirzepatide on average lost up to one fifth of their body weight – and notably, about nine out of ten participants taking tirzepatide lost weight. These results are significantly higher than the placebo arm and underscore the importance of this study."

Tirzepatide also met the co-primary and all key secondary endpoints for the treatment-regimen estimandiii, including:

1. Average body weight reductions: 15.0% (5 mg), 19.5% (10 mg) and 20.9% (15 mg) compared to 3.1% with placebo.

2. Percentage of participants achieving body weight reductions of ≥5%: 85% (5 mg), 89% (10 mg) and 91% (15 mg) compared to 35% with placebo.

3. Percentage of participants achieving ≥10% body weight reductions: 69% (5 mg, not controlled for type 1 error), 78% (10 mg) and 84% (15 mg) compared to 19% with placebo.

4. Percentage of participants achieving ≥15% body weight reductions: 48% (5 mg, not controlled for type 1 error), 67% (10 mg) and 71% (15 mg) compared to 9% with placebo.

5. Percentage of participants achieving body weight reductions of ≥20%: 30% (5 mg, not controlled for type 1 error), 50% (10 mg), and 57% (15 mg) compared to 3.1% with placebo.

6. Change in waist circumference from baseline: -14.0 cm (5 mg, not controlled for type 1 error), ‑17.7 cm (10 mg) and -18.5 cm (15 mg) compared to -4.0 cm with placebo.

7. Percentage of participants taking tirzepatide achieving ≥25% body weight reductions (not controlled for type 1 error): 15.3% (5 mg), 32.3% (10 mg) and 36.2% (15 mg) compared to 1.5% with placebo.

"Lilly is proud to share the detailed results from SURMOUNT-1, which reinforce our confidence in the potential of tirzepatide as a treatment for obesity, as participants lost between an average of 35 and 52 pounds throughout the trial," said Mike Mason, president, Lilly Diabetes. "Lilly aims to transform how diseases like obesity are understood and treated, and today's simultaneous publication and presentation of these results mark an important milestone in our mission."

The overall safety and tolerability profile of tirzepatide was similar to other incretin-based therapies approved for the treatment of obesity. The most commonly reported adverse events were gastrointestinal-related and generally mild to moderate in severity, usually occurring during the dose escalation period. For those treated with tirzepatide (5 mg, 10 mg and 15 mg, respectively), nausea (24.6%, 33.3%, 31.0%), diarrhea (18.7%, 21.2%, 23.0%), constipation (16.8%, 17.1%, 11.7%), and vomiting (8.3%, 10.7%, 12.2%) were more frequently experienced compared to placebo (9.5% [nausea], 7.3% [diarrhea], 5.8% [constipation], 1.7% [vomiting]).

Treatment discontinuation rates due to adverse events were 4.3% (5 mg), 7.1% (10 mg), 6.2% (15 mg) and 2.6% (placebo). The overall treatment discontinuation rates were 14.3% (5 mg), 16.4% (10 mg), 15.1% (15 mg) and 26.4% (placebo). The overall trial completion rates were 89% (5 mg), 88% (10 mg), 90% (15 mg) and 77% (placebo).