A recent international clinical trial has demonstrated that an experimental oral drug, orforglipron, significantly aids weight loss and improves heart and metabolic risk factors among patients with obesity. The results from the ATTAIN-1 trial, led by researchers from Weill Cornell Medicine, McMaster University, York University, and other institutions, were published on September 17, 2023, in the New England Journal of Medicine.
The large-scale trial involved 3,127 non-diabetic patients diagnosed with obesity or overweight, many of whom also faced related complications such as hypertension. Participants were randomly assigned to receive either a placebo or one of three daily doses of orforglipron (6 mg, 12 mg, or 36 mg) alongside a structured diet and increased physical activity. Over a period of 72 weeks, those in the treatment groups lost an average of 7.8%, 9.3%, and 12.4% of their initial body weight, respectively, compared to only 2.1% in the placebo group.
The side effects reported were consistent with those experienced by patients taking other GLP-1 medications, primarily presenting as mild to moderate gastrointestinal issues including nausea, vomiting, and diarrhea.
Dr. Louis Aronne, director of the Comprehensive Weight Control Center at Weill Cornell Medicine and a lead investigator of the ATTAIN-1 trial, noted, “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 trial results indicate that orforglipron could represent a significant milestone in the treatment of obesity. Dr. Aronne highlighted that the production and distribution of a small molecule like orforglipron are less costly and simpler than that of injectable drugs, thus improving accessibility for many patients.
While the average weight loss observed with orforglipron is lower than that seen with injectable GLP-1 therapies such as semaglutide or tirzepatide, the improvements in key health indicators were notable. Participants taking orforglipron exhibited greater reductions in waist circumference, systolic blood pressure, non-HDL cholesterol, triglyceride levels, and glycated hemoglobin compared to those receiving a placebo.
The rise of injectable GLP-1 drugs has significantly transformed obesity treatment over recent years. These medications can lead to long-term weight loss exceeding 15% and improve blood sugar control, subsequently lowering risks of heart attacks, strokes, chronic kidney disease, sleep apnea, and other complications associated with obesity.
Unlike injectable GLP-1 drugs, which are peptides and require careful handling, orforglipron is designed as a small molecule drug that can be taken orally. This characteristic enhances its appeal, particularly for patients who may find injections daunting or unfeasible.
The ATTAIN-1 trial was sponsored by Eli Lilly, the manufacturer of orforglipron and the injectable GLP-1 drug tirzepatide, marketed under the brand names Mounjaro for type 2 diabetes and Zepbound for chronic weight loss. The trial was conducted across 137 sites in nine countries, including the United States, Canada, Japan, Brazil, Spain, and Saudi Arabia.
It is noteworthy that Dr. Aronne serves as a paid consultant and is a member of the advisory board for Eli Lilly, the study sponsor and producer of orforglipron.
The findings from the ATTAIN-1 trial could pave the way for new therapeutic options for individuals struggling with obesity, highlighting the ongoing need for effective treatments in this growing global health crisis.
