American Diabetes Scientific Sessions, 23 June 2024 – The data from three studies investigating glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonists in patients with obesity was recently presented at a late-breaking session at the American Diabetes Association’s 84th Scientific Sessions in Orlando.
Reduction of Body Weight and Blood Pressure with Dual GLP-1/GIP Receptor Agonist HRS9531
A Phase 2 double-blind, randomized, placebo-controlled study investigated HRS9531 in obese adults without diabetes, demonstrating reductions in body weight, blood pressure, blood sugar, and triglycerides.
HRS9531, a drug in development, targets both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors for weight management by influencing insulin and blood sugar control.
Results of the trial conducted among 249 Chinese adults with a body mass index of 28-40 kg/m² demonstrated a body mass index (BMI) reduction from 5.4% -16.8% across escalating doses. Most adverse events (AEs) were mild or moderate, and the most common AEs were nausea, diarrhoea, decreased appetite, and vomiting, occurring primarily during dose escalation. The overall safety and tolerability profile of HRS9531 is consistent with other GLP-1 agonists.
Dr. Xiaoying Li, MD, PhD, Professor and Director of the Department of Endocrinology and Metabolism at Zhongshan Hospital Fudan University, China, expressed optimism about the study's findings. "We were pleased to see that HRS9531 could be a potentially promising treatment for weight management," said Dr. Li, the senior author of the study. "This approach has the potential to enhance patients' overall health and significantly reduce the societal burden of obesity."
Phase 3 study with HRS9531 is currently ongoing and multi-regional studies being planned.
Phase 2 MOMENTUM Trial Shows 15.6% Average Weight Loss for Patients with Overweight or Obesity
Pemvidutide (AltImmune), a GLP-1/Glucagon dual receptor agonist, is a drug currently in development for obesity and metabolic-dysfunction associated steatohepatitis (MASH).
A Phase 2 study evaluating the safety and efficacy of pemvidutide, MOMENTUM (NCT05295875) revealed promising results at ADA, showing that the drug significantly reduced body weight and serum lipids over 48 weeks of treatment.
This randomized, placebo-controlled trial enrolled 391 subjects with overweight or obesity without diabetes, and administered either pemvidutide or placebo at three dose levels (1.2, 1.8, 2.4mg) weekly for 48 weeks. Those who had received the highest pemvidutide dose had lost an average of 15.6% of their total body weight, and the treatment appeared to be safe and well-tolerated. Additionally, results from a body composition sub-study were presented indicating class-leading preservation of lean mass, with only 21.9% attributable to lean mass and 78.1% of weight loss due to fat.
Louis J. Aronne, MD, FACP, DABOM, Weill Cornell Medicine, New York City, NY, and primary investigator of the trial said “These findings demonstrated that the use of pemvidutide may have important effects on the quality of weight loss and cardiometabolic-associated comorbidities of obesity”.
Larger phase 3 registrational trials aiming to demonstrate both the safety and clinical benefit of pemvidutide are in preparation, as well as a study on patients with excess liver fat and MASH.
Retatrutide Found to Improve Insulin’s Ability to Reduce Blood Sugar in Patients with Type 2 Diabetes
A new study evaluating retatrutide, a GIP/GLP-1 and glucagon receptor agonist, analysed biomarkers to observe how treatment with retatrutide affects pancreatic beta cells that make insulin, as well as biomarkers associated with the body’s ability to respond to insulin to lower blood sugar.
Exploratory biomarker research within phase 2 clinical trials was examined to further understand on the molecular level how retatrutide may work. In the study, retatrutide was found to increase markers of well-functioning insulin-producing beta cells (HOMA2-B) and the ability of insulin to lower blood sugar (adiponectin). The results also demonstrated how retatrutide decreased markers of stress on insulin-producing cells, as assessed by measuring immature insulin (proinsulin) and reduction in a marker of insulin resistance (HOMA2-IR).
Dr Melissa K Thomas, MD, PhD, Vice President of Diabetes and Metabolic Research at Lilly Research Laboratories, Indianapolis, and one of the investigators conducting the study, said, "We are encouraged to see that people living with either obesity or with type 2 diabetes in our clinical studies had lowered blood sugar and had improved responses to insulin."
Several Phase 3 clinical trials studying retatrutide in people living with type 2 diabetes or obesity without type 2 diabetes are in progress, including the TRIUMPH and TRANSCEND Phase 3 trials.
Sources:
American Diabetes Association. (2024, June 23). The American Diabetes Association Highlights Innovations in New Drug Therapies for Patients with Obesity [Press Release].
Xiaoying Li, et al. Diabetes 2024. 1861-LB: Efficacy and Safety of HRS9531, a Novel Dual GLP-1/GIP Receptor Agonist, in Obese Adults—A Phase 2 Trial. DOI: 10.2337/db24-1861-LB
Aronne LJ, et al. ADA 2024. Pemvidutide, a GLP-1/Glucagon Dual Receptor Agonist, in Subjects with Overweight or Obesity—A 48-Week, Placebo-Controlled, Phase 2 (MOMENTUM) Trial [PowerPoint Presentation].
Thomas, MK. ADA 2024. Weighing Opportunities of Incretin-Based Therapy in Obesity Retatrutide, an Agonist of GIP, GLP-1, and Glucagon Receptors, Improves Markers of Pancreatic Beta-Cell Function and Insulin Sensitivity [PowerPoint Presentation.