SURMOUNT-1: Adults achieve weight loss of 16% or more at 72 weeks with tirzepatide
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Adults with overweight or obesity taking the once-weekly GIP/GLP-1 receptor agonist tirzepatide achieved a mean weight loss of at least 16% at 72 weeks, according to topline results from the SURMOUNT-1 clinical trial.
In a phase 3 trial with 2,539 participants, tirzepatide (Eli Lilly) met both primary endpoints for mean percentage change in body weight from baseline and percentage of participants with a 5% reduction in body weight compared with placebo. Adults randomly assigned to receive tirzepatide had a mean weight loss of 16% with 5 mg, 21.4% with 10 mg, and 22.5% with 15 mg compared with a 2.4% mean weight loss for those assigned placebo. Of those assigned tirzepatide, 89% achieved a weight loss of at least 5% compared with 28% in the placebo group.
“This study shows that highly significant weight loss, in line with what is achieved with surgical procedures, can be achieved with tirzepatide,” Louis J. Aronne, MD, FACP, DABOM, the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medicine at New York-Presbyterian/Weill Cornell Medical Center and investigator in the SURMOUNT-1 trial, told Healio. “The mean BMI was about 38 kg/m2 to start and was reduced to about 30 kg/m2 with many subjects getting into the normal range.”
Tirzepatide met all key secondary endpoints, with 55% of those receiving 10 mg and 63% of those receiving 15 mg achieving a body weight reduction of at least 20% compared with 1.3% of the placebo group. In an additional secondary endpoint analysis not controlled for type 1 error, 32% of those receiving 5 mg tirzepatide lost at least 20% of body weight, according to the release.
“For perspective, a 5% weight loss reduces the risk of developing diabetes by 50%, and a 10% weight loss reduces it by 80%,” Aronne said. “Lap band produces about 17% weight loss, and sleeve gastrectomy 25% mean weight loss. The gap between diets and bariatric surgery is being filled by medical therapy.”
The safety and tolerability profile for tirzepatide was similar to that those of other incretin-based therapies approved for obesity treatment. Most side effects were mild to moderate; the most common were nausea, diarrhea, constipation and vomiting.
Participants with prediabetes at the start of the trial will remain enrolled for an additional 104 weeks beyond the initial 72-week trial period to evaluate the impact of body weight and potential differences in type 2 diabetes progression with tirzepatide compared with placebo.
The SURMOUNT-1 results will be presented at an upcoming medical meeting and submitted to a peer-reviewed journal, according to the release. Additional studies are ongoing.
Perspective
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This is extremely exciting, albeit preliminary data showing bariatric surgery-level weight loss from a medication, one that likely affords numerous other metabolic benefits, including diabetes improvement and prevention and possibly long-term cardiovascular benefit. Continued development of tirzepatide and similar agents could portend a sea change in obesity treatment, similar to how cholesterol and heart disease management was transformed by the advent of statin medications and how HIV management was transformed by antiretroviral medications.
Perspective
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This is outstanding news. Looking across trials, tirzepatide would become the most effective weight-loss medication available, assuming it is approved by the FDA. Over half of the patients on the 10 mg dose and 63% on the 15 mg dose lost more than 20% of their body weight. That 20% takes you past the weight loss achieved with Lap-Band and well within the weight loss achieved with sleeve gastrectomy and Roux-en-Y gastric bypass surgery.
This amount of weight loss is sufficient to prevent or treat almost all of the complications of obesity, whether it’s preventing diabetes, treating diabetes, treating obstructive sleep apnea, hypertension or osteoarthritis. From the complication-centric approach to care as advocated for by the American Association of Clinical Endocrinology obesity guidelines, this is very important. Our objective isn’t just to get people to lose weight, it’s to improve their health, and we interpret that to mean preventing or treating the complications of the disease that confer morbidity or mortality.
I have proposed criteria for second-generation obesity medications based on health benefits and the potential to transform obesity care, which include mean placebo-subtracted weight loss of more than 10% and weight loss of 15% or more in conjunction with lifestyle intervention in randomized trials. Up until now, semaglutide 2.4 mg/week was the only medication meeting these criteria. Based on data from this clinical trial, tirzepatide would be another second-generation medication for treating obesity.
The caution here would be we do not know what the side effect profile is. We do know, as expected, it caused some nausea, vomiting and a certain level of medication discontinuation due to these side effects. The levels are comparable to what we see with other GLP-1 receptor agonists. We have to see the safety data in more detail. But this is outstanding news, and hopefully tirzepatide will be approved. The addition of tirzepatide to existing medications provides us with an exciting new option allowing us to better individualize care for patients with obesity.
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