A recent phase III clinical trial has demonstrated that an experimental oral GLP-1 drug, known as orforglipron, can significantly aid in weight loss for patients with obesity. Conducted by researchers from Weill Cornell Medicine, McMaster University, York University, among others, the findings from the trial, referred to as the ATTAIN-1 trial, were published on September 17, 2023, in the New England Journal of Medicine.
The trial involved 3,127 non-diabetic patients who were either overweight or had obesity-related complications, such as hypertension. Participants were randomized to receive a placebo or one of three daily doses of orforglipron (6 mg, 12 mg, or 36 mg), alongside a structured diet and exercise regimen. Over a period of 72 weeks, patients taking the low-, medium-, and high-dose orforglipron lost an average of 7.8%, 9.3%, and 12.4% of their initial body weight, respectively. In comparison, the placebo group experienced a modest loss of 2.1%.
Side effects reported in the trial were consistent with other GLP-1 medications, including mild to moderate gastrointestinal symptoms like nausea, vomiting, and diarrhea. Dr. Louis Aronne, director of the Comprehensive Weight Control Center and a lead investigator of the ATTAIN-1 trial, highlighted the significance of these results. He stated, “The findings suggest that orforglipron could offer an important new option for people with obesity, especially those reluctant to use injections or who live in places where cold storage for injectable medications is limited.”
The ATTAIN-1 trial marks a significant advancement in obesity treatment, particularly given the global demand for effective solutions. Dr. Aronne noted that orforglipron, as a small molecule drug, is less expensive to distribute and easier to store than injectable alternatives. This could improve accessibility for those in need.
While the average weight loss observed was somewhat less than what is typically associated with injectable GLP-1 therapies such as semaglutide or tirzepatide, the trial also recorded substantial improvements in heart and metabolic risk factors. Patients taking orforglipron showed greater reductions in waist circumference, systolic blood pressure, non-HDL cholesterol, triglyceride levels, and glycated hemoglobin compared to those receiving the placebo.
Injectable GLP-1 medications have transformed the landscape of obesity and type 2 diabetes treatment in recent years. Patients using these drugs over extended periods can lose over 15% of their body weight and experience improved blood sugar control, decreasing the risk of heart attacks, strokes, chronic kidney disease, and other complications associated with obesity.
Unlike injectable GLP-1 drugs, which are peptides that require protection from stomach acids and enzymes to be effective, orforglipron’s small molecule formulation allows it to be taken orally. The trial involved 137 sites across nine countries, including the United States, Canada, Japan, Brazil, Spain, and Saudi Arabia.
Eli Lilly, the company that produces orforglipron, also manufactures the injectable GLP-1 drug tirzepatide, marketed under the brand names Mounjaro for type 2 diabetes and Zepbound for chronic weight loss. Dr. Aronne serves as a paid consultant and advisory board member for Eli Lilly, which sponsored the study.
As healthcare professionals and researchers continue to seek innovative treatments for obesity, the promising results from the ATTAIN-1 trial offer hope for those struggling with weight management and related health issues.
