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Studies of Novel, Highly Effective Antiobesity Medications Headline 83rd ADA Scientific Sessions


Retatrutide, survodutide, orforglipron. The 3 new GLP-1 agonist-based AOMs showed weight loss of up to 20% and are well worth watching.

Retatrutide, survodutide, orforglipron. If the names of these 3 GLP-1 receptor agonist-based antiobesity medications don't sound familiar now, they are likely to in the coming months as results of phase 2 clinical trials demonstrated average weight loss of up to 24%, 19%, and 15%, respectively, for the investigational agents. Phase 3 trials are planned for each.

Significant reductions in body weight, improvement in multiple cardiometabolic measures, and oral delivery lead benefits of the new formulations. Find quotes on findings from lead investigators below and links to the study highlights.

©galyna_p/Adobe Stock  Global Diabetes Prevalence Will Double by 2050, Affecting 1.3 Billion People: New Predictions
Ania Jastreboff, MD, PhD

Novel MOA. "Participants treated with the highest dose of retatrutide achieved a mean weight reduction of 24.2%; this translates to an average absolute weight reduction of about 58 pounds over 11 months of the study. Given that participants had not yet reached a weight plateau at the time the study ended, it appears that full weight reduction efficacy was not yet attained."

© Fandorina Liza/Adobe stock
Sean Wharton, MD, PharmD

An oral option. "We recognize that obesity is a global epidemic and there is a need for a variety of effective medications and administration routes." Specifically, “there is an unmet need for an oral, incretin-based therapy with efficacy similar to that of injectable GLP-1 receptor agonists.” Given that weight loss had not reached a plateau at the 36-week point, they continued, it's possible that longer treatment duration will result in additional reduction in body weight.

Survodutide, Novel Dual GLP-1/Glucagon Agonist, Achieves ~19% Weight Loss in People with Overweight, Obesity
Carel le Roux, MBChB, PhD

Target: glucagon. “By activating both the glucagon and GLP-1 receptors, survodutide may inhibit both appetite and improve energy expenditure. The findings not only show significant weight loss with increasing doses of survodutide, but we also saw a favorable safety profile, reinforcing the potential clinical benefits.” Among survodutide-treated participants in a phase 2 study, more than half lost more than 50% of baseline bodyweight.

©design36/stock.adobe.com SURMOUNT-2: Tirzepatide Treatment Leads to Average 15% Weight Loss in Adults with T2D, Obesity  SURMOUNT-2: Tirzepatide Treatment Leads to Average 15% Weight Loss in Adults with T2D, Obesity
W Timothy Garvey, MD

T2D + obesity. “Tirzepatide reduces weight in patients who have both obesity and type 2 diabetes to an extent we haven’t seen before, greater than any other clinical trials and other weight loss medications. With a new drug like tirzepatide, it becomes clear we need a weight-centric approach to treating type 2 diabetes when obesity is also present, two conditions that are interwoven for so many Americans.”

Oral Semaglutide 50 mg May be Effective Option for Obesity Treatment, According to OASIS 1 Study Authors
Filip K Knop, MD, PhD

Hi-dose SEMA. “To our knowledge, this was the first trial to assess the body weight-lowering effect of an oral GLP-1 analogue in adults with overweight or obesity, without type 2 diabetes. In this population, oral semaglutide 50 mg induced clinically meaningful reductions in body weight, with accompanying improvements in cardiometabolic risk factors.”

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