Nutrient-stimulated, hormone-based antiobesity medications
Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:
Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.
Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.
Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.
The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.
And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.
The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.
Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.
CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2 (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively.
Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.
Survodutide is being studied in the phase 3 SYNCHRONIZE trials.
Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.
With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”
TRIUMPH phase 3 studies of retatrutide are ongoing.
“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.
Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.
The phase 3 OASIS study of oral semaglutide in obesity is ongoing.
Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.
The phase 3 ATTAIN study of orforglipron in obesity is ongoing.
AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.