TOS members unveil new research about anti-obesity medications at ADA annual meeting

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Multiple members of The Obesity Society (TOS) unveiled new research about several anti-obesity medications in development at this year's annual meeting of the American Diabetes Association (ADA) held June 23–26. The results were simultaneously published in major publications such as The New England Journal of Medicine and The Lancet.

TOS members Ania M. Jastreboff, MD, PhD, Yale University School of Medicine, director of the Yale Obesity Research Center (Y-Weight), and part of TOS's Governing Board, and TOS Past President Lee M. Kaplan, MD, PhD, director of The Obesity and Metabolism Institute in Boston, Mass., along with other co-authors presented the results of a phase 2 trial of retatrutide for the treatment of obesity. Retatrutide is a tri-agonist of the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) and glucagon receptors.

In nearly 340 adults with obesity, the study found that retatrutide treatment resulted in substantial reductions in body weight. Participants were randomly assigned to receive once-weekly subcutaneous retatrutide (1 mg, 4 mg [initial dose, 2 mg], 4 mg [initial dose, 4 mg], 8 mg [initial dose, 2 mg], 8 mg [initial dose, 4 mg], or 12 mg [initial dose, 2 mg]) or placebo for 48 weeks. At the end point, a weight reduction of 5% or more, 10% or more, and 15% or more had occurred in 92%, 75%, and 60%, respectively, of the participants who received 4 mg of retatrutide; 100%, 91%, and 75% of those who received 8 mg; 100%, 93%, and 83% of those who received 12 mg; and 27%, 9%, and 2% of those who received a placebo.

"It is striking that on average, participants with obesity taking the highest dose of retatrutide lost nearly a quarter of their body weight, on average 58 lbs., with 11 months of treatment. Additionally, participants had not yet reached a weight plateau at the time the study was stopped, meaning their weight was still decreasing rather than at steady state. Phase 3 trials will investigate weight reduction efficacy with longer duration of treatment with retatrutide," said Jastreboff.

The New England Journal of Medicine article describing the study can be found here.

Jastreboff and TOS member Nadia Ahmad, MD, associate vice president at Eli Lilly and Co. were both co-authors on the study discussing tirzepatide once weekly for the treatment of obesity for people with type 2 diabetes-;SURMOUNT-2 trial.

In this 72-week trial in adults living with obesity and type 2 diabetes, once-weekly tirzepatide 10 mg and 15 mg provided substantial and clinically meaningful reduction in body weight, with a safety profile that was similar to other incretin-based therapies for weight management.

Researchers assessed more than 1,500 adults for eligibility between March 2021 and April 2023. Participants were randomly assigned and received at least one dose of tirzepatide 10 mg, tirzepatide 15 mg or placebo. More participants treated with tirzepatide versus placebo met body weight reduction thresholds of 5% or higher (79–83% vs. 32%), according to the study's results.

The study's results can be found in The Lancet.

TOS member Sean Wharton, MD, PharmD, of Wharton Medical Clinic and part of TOS's Governing Board presented results in an oral abstract presentation about an experimental medication called orforglipron. TOS member Manige Konig, MD, PhD, executive director of clinical research incretins and incretin combinations with Eli Lilly and Co. was a co-author on the study.

The medication comes from the class of anti-obesity and diabetes medications called GLP-1 agonists that include Ozempic and Wegovy. However, unlike the latter two medications, orforglipron is administered as a once-a-day pill rather than an injection.

In this phase 2, randomized, double-blind trial, 272 adults with obesity or with overweight plus at least one weight-related co-existing condition and without diabetes were enrolled. Participants were randomly assigned to receive orforglipron at one of four doses (12, 24, 36 or 45 mg) or placebo once daily for 36 weeks. A weight reduction of at least 10% by week 36 occurred in 46 to 75% of the participants who received orforglipron, as compared with 9% who received placebo.

"By all accounts this is a major breakthrough in medicine to have a non-peptide, small chemical molecule activate the GLP-1 receptor and achieve such significant weight loss. The medication is once daily and does not require restriction of food, water or other medications. This heralds the possibility of medications that are easily made, transported and administered. This would have a significant impact on the equity of care in the field of obesity medicine," said Wharton, the study's lead author.

The New England Journal of Medicine article describing the study can be found here.

TOS President-elect Jamy Ard, MD, FTOS, of Wake Forest University School of Medicine chaired the SURMOUNT-2 trial symposium, which included results and the potential role of tirzepatide in treating obesity in people with type 2 diabetes. The session featured an overview of the study design, efficacy and safety data from the phase 3 randomized controlled trial of tirzepatide in participants with type 2 diabetes who have obesity or are overweight.

"I want to highlight how exciting this field is right now. We've never before had medications that have been this effective," said TOS Spokesperson Katherine H. Saunders, MD, DABOM, an obesity expert at Weill Cornell Medicine in New York City and a co-founder of Intellihealth, a software and clinical services company scaling and democratizing access to comprehensive medical obesity treatment. "Obesity is such a complex, heterogeneous disease, so it's not going to be that one medication is the answer for everybody. We need as many tools as we can get in our armamentarium so that we have effective options for everybody."

Funding for all three studies was provided by Eli Lilly and Co.

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