Orforglipron Shows Superior Reduction in Hemoglobin A1c for Patients With Type 2 Diabetes
Investigators find that orforglipron lowered A1c by an average of 1.3% to 1.6% from a baseline of 8% across 3 different dosages.
Orforglipron met the primary end point of superior hemoglobin A1c reduction compared to the placebo at 40 weeks for patients with type 2 diabetes (T2D), according to topline results from the phase 3 ACHIEVE-1 (NCT05971940) study.1
Investigators find that orforglipron lowered A1c by an average of 1.3% to 1.6% from a baseline of 8% across 3 different dosages. | Image Credit: New Africa - stock.adobe.com
"ACHIEVE-1 is the first of 7 phase 3 studies examining the safety and efficacy of orforglipron across people with diabetes and obesity. We are pleased to see that our latest incretin medicine meets our expectations for safety and tolerability, glucose control, and weight loss, and we look forward to additional data readouts later this year," David A. Ricks, chair and CEO at Eli Lilly, said in a news release.1 "As a convenient once daily pill, orforglipron may provide a new option and, if approved, could be readily manufactured and launched at scale for use by people around the world."
Investigators of the study aimed to determine the safety and efficacy of orforglipron compared with the placebo for patients with T2D and inadequate glycemic control with diet and exercise alone. The trial lasted for approximately 54 weeks and could include up to 13 visits, according to the clinical trial information. Patients included had T2D, an A1c of 7% to 9.5% despite exercise and diet, were naïve to insulin therapy, were of a stable weight, and had a body mass index of 23 kg/m2 or greater at screening. Investigators excluded patients with type 1 diabetes, a history of ketoacidosis or hyperosmolar state within 6 months prior to screening, currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema, congestive heart failure, or acute or chronic pancreatitis.2,3
Investigators randomized treatment to either 1 of 3 doses of orforglipron or the placebo administered orally. The primary outcome was hemoglobin A1c at 40 weeks. Secondary outcomes included percentage of patients with an A1c of less than 7% and 6.5% or less at week 40, change from baseline in fasting serum glucose, body weight, daily average 7-point self-monitored blood glucose, systolic blood pressure, non-high-density lipoprotein cholesterol, and Short Form 36 Version 2 acute form domain scores, and percentage change from baseline in body weight, triglycerides, and weight loss of 5% or more.2
The study took place from August 8, 2023, to March 31, 2025. Investigators found that orforglipron lowered A1c by an average of 1.3% to 1.6% from a baseline of 8%. For the 3 mg dose of orforglipron, A1c was reduced by 1.3%. Additionally, A1c was lowered by 1.6% for the 12 mg dose and 1.5% for the 36 mg dose compared to 0.1% for the placebo. Furthermore, for secondary endpoints, approximately more than 65% of patients taking the 36 mg dose had an A1c of less than or equal to 6.5%.1,3
For secondary end points of weight reduction, patients taking the 3 mg had a reduction from baseline of 90.2 kg of 4.7%, 6.1% for the 12 mg dose, and 7.9% for the 36 mg dose compared to 1.6% for the placebo. Weight reduction from baseline was 4.4 kg, 5.5 kg, and 7.3 kg, respectively, compared with 1.3 kg for the placebo. Investigators noted that patients did not reach a weight plateau, showing that full weight reduction was not reached.1
As for safety, the most commonly reported adverse events were gastrointestinal-related and generally mild to moderate in severity, including diarrhea, nausea, dyspepsia, constipation, and vomiting. Discontinuation due to AEs was 6% for the 3 mg group, 4% for 12 mg, 8% for 36 mg, and 1% for the placebo.1
READ MORE: Diabetes Resource Center
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