A clinical trial led by Deborah Horn, DO, MPH, professor and director of obesity medicine at McGovern Medical School at UTHealth Houston, has shown that a new oral GLP-1 medication may help adults with obesity and Type 2 diabetes lose more weight and improve blood sugar levels compared to a placebo. The results of the ATTAIN-2 trial were published in The Lancet.
The medication studied is orforglipron, a daily pill designed for adults with obesity. Unlike existing GLP-1 treatments that require injections and cold storage, orforglipron is taken orally once a day without restrictions on food or water intake and does not require refrigeration.
“The opportunity for an oral GLP-1 medication with highly effective weight loss that is simpler to take may provide increased access and opportunities for better health for our patients with obesity and diabetes,” said Horn.
Orforglipron works by stimulating insulin release while reducing glucagon secretion, which lowers blood sugar levels and helps control appetite. Previous research indicated that orforglipron could reduce body weight by over 12% in adults with obesity but without diabetes. The current study extended this research to people who also have Type 2 diabetes.
The ATTAIN-2 trial was conducted over 72 weeks at 136 sites in ten countries, involving 1,613 adults. Participants started on a low dose of orforglipron, which was gradually increased during the study period. They were also encouraged to follow dietary guidelines focused on portion control and increasing protein and fiber intake rather than following strict calorie reduction plans common in other trials. Physical activity recommendations included at least 150 minutes per week.
Results showed that participants taking up to 6 mg of orforglipron lost an average of 5.5% of their body weight after 72 weeks; those taking 12 mg lost an average of 7.8%; those taking the highest dose (36 mg) lost about 10.5%. By comparison, the placebo group averaged only a 2.2% reduction in body weight. The pill also improved blood sugar levels, with side effects limited mainly to mild-to-moderate gastrointestinal issues similar to those seen with injectable GLP-1 medications.
“We know it is harder for individuals with diabetes to lose weight. It is exciting to have an oral medication that provides double-digit weight loss, which on average was 23 lbs. Once FDA approved, orforglipron is scheduled to be available in 2026 at a significantly decreased cost compared to current injectables. This could position it to be the ‘metformin’ of obesity and become widely covered by insurance plans, opening the door to treatment for all,” Horn said.
Other researchers involved came from institutions including Pennington Biomedical Research Center (Louisiana), Eli Lilly and Company (Indiana), Centro Paulista De Investigação Clínica (Brazil), PLA General Hospital (China), Korea University (South Korea), University Hospital Hamburg-Eppendorf (Germany), and Swansea University Medical School (UK).
