New Oral Weight Loss Pill Shows Promise in Major Clinical Trial
A new oral medication, orforglipron, has demonstrated notable weight loss and improvements in metabolic health in a large, international phase 3 clinical trial. Led by researchers at Weill Cornell Medicine, McMaster University, York University, and other institutions, the ATTAIN-1 trial involved 3,127 individuals with obesity or overweight and related health issues like hypertension, but without diabetes. the findings were published September 17th in the New England Journal of Medicine.
Participants were randomly assigned to receive either a placebo or one of three daily doses of orforglipron – 6mg, 12mg, or 36mg - alongside a healthy diet and regular physical activity. Over 72 weeks, those receiving the low, medium, and high doses of the drug experienced average weight losses of 7.8%,9.3%, and 12.4% of their initial body weight, respectively. This contrasts sharply with the 2.1% weight loss observed in the placebo group.
The study also revealed substantial improvements in key heart and metabolic risk factors for those taking orforglipron, including reductions in waist circumference, systolic blood pressure, non-HDL cholesterol, triglyceride levels, and glycated hemoglobin. Side effects reported were consistent with other GLP-1 medications, primarily mild to moderate gastrointestinal symptoms like nausea, vomiting, and diarrhea.
“Orforglipron could be a valuable new treatment option for individuals struggling with obesity,” explains Dr.Louis Aronne, director of the Extensive Weight Control Center and the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medicine, and a lead investigator in the trial. “Its oral form offers advantages over injectable medications, notably for those hesitant about injections or living in areas with limited access to cold storage.” He further noted the potential for lower costs and easier scalability with a small molecule drug like orforglipron, crucial factors in global accessibility.
While the average weight loss observed was slightly lower than that achieved with injectable GLP-1 therapies like semaglutide and tirzepatide,the positive impact on metabolic health was considerable. Orforglipron distinguishes itself from existing injectable GLP-1 drugs by being a daily pill.This is absolutely possible as it’s a “small molecule” drug, able to withstand the digestive process, unlike peptide-based injectables which are broken down by the stomach. Both orforglipron and injectable GLP-1s work by mimicking the effects of the naturally occurring GLP-1 hormone, which regulates appetite and digestion.
The ATTAIN-1 trial was conducted across 137 sites in nine countries – including the United States, Canada, Japan, Brazil, Spain, and Saudi Arabia – and was sponsored by Eli Lilly, the manufacturer of orforglipron, and also the injectable GLP-1 drugs tirzepatide (marketed as Mounjaro for type 2 diabetes and Zepbound for chronic weight loss).
It is indeed crucial to note that Dr. louis Aronne is a paid consultant and advisory board member for Eli Lilly and Company,the sponsor and manufacturer of orforglipron.
