Orforglipron Demonstrates Superior Glycemic Control for Type 2 Diabetes

Orforglipron showed superior glycemic control in 2 phase 3 trials, further enforcing the drug’s potential as a treatment for type 2 diabetes (T2D). In both trials, the drug met all primary and secondary end points at 40 weeks, which included efficacy and treatment-regimen estimands.¹

"Orforglipron has now demonstrated superiority over 2 active comparators in clinical trials for type 2 diabetes," Jeff Emmick, MD, PhD, senior vice president of product development at Lilly Cardiometabolic Health, said in a news release.¹ "In ACHIEVE-2, orforglipron outperformed dapagliflozin, a commonly used SGLT-2 therapy, and in ACHIEVE-3, showed greater efficacy than oral semaglutide. The findings from ACHIEVE-5 add to this momentum, showing significant A_1c reduction and weight loss when used in combination with titrated basal insulin. Together, these results reinforce orforglipron's potential to become a new standard of care for people living with type 2 diabetes."

The 2 studies included the ACHIEVE-2 (NCT06192108) and ACHIEVE-5 (NCT06109311) trials. In ACHIEVE-2, investigators assessed the safety and efficacy of orforglipron compared with dapagliflozin to improve blood sugar control for patients with diabetes who have inadequate hemoglobin A_1c (HbA_1c) using metformin. The primary end point included change from baseline HbA_1c at week 40. Secondary outcomes included change from baseline in HbA_1c at week 40, percentage of individuals achieving an HbA_1c of less than 7%, percentage of individuals who achieve HbA_1c of 6.5% or less, and percentage change in body weight, non-high-density lipoprotein cholesterol (HDL-C), triglycerides, systolic blood pressure, diastolic blood pressure, fasting serum glucose, and total cholesterol.²

In ACHIEVE-5, investigators aimed to determine the safety of orforglipron for patients with T2D who have inadequate HbA_1c control with insulin glargine with or without metformin and/or sodium-glucose contransporter-2 inhibitor. The primary outcome included change from baseline HbA_1c at week 40, and secondary outcomes included percentage of patients with an HbA_1c less than 7%, percentage of patients who achieved an HbA_1c of 6.5% or less, change in fasting serum glucose, body weight, nonHDL-C, triglycerides, systolic blood pressure, and daily insulin glargine.³

The new data shows that both trials met the primary end points for the 3 doses: 3 mg, 12 mg, and 36 mg, as well as demonstrated weight loss and improvements in cardiovascular risk factors. In ACHIEVE-2, the treatment-regimen estimand in change in HbA_1c from the baseline of 8.1% decreased by 1.2%, 1.5%, and 1.6%, respectively, compared with 0.8% for dapagliflozin. In ACHIEVE-5, the treatment-regimen estimand in change in HbA_1c from the baseline of 8.5% decreased by 1.6%, 1.9%, and 1.8% compared with 0.8%, respectively.¹

For both trials, the overall safety and tolerability were consistent with previous studies, with the most common adverse events being gastrointestinal in nature. Detailed results will be presented at a future medical meeting and published in a peer-reviewed journal.¹

READ MORE: Diabetes Resource Center

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REFERENCES

1. Lilly’s oral GLP-1, orforglipron, demonstrated superior glycemic control in two successful phase 3 trials, reconfirming its potential as a foundational treatment in type 2 diabetes. News release. Eli Lilly. October 15, 2025. Accessed October 16, 2025. https://www.prnewswire.com/news-releases/lillys-oral-glp-1-orforglipron-demonstrated-superior-glycemic-control-in-two-successful-phase-3-trials-reconfirming-its-potential-as-a-foundational-treatment-in-type-2-diabetes-302584124.html

2. A study of orforglipron (LY3502970) compared with dapagliflozin in adult participants with type 2 diabetes and inadequate glycemic control with metformin (ACHIEVE-2). ClinicalTrials.gov identification: NCT06192108. Updated July 2, 2025. Accessed October 16, 2025. https://clinicaltrials.gov/study/NCT06192108

3. A study of orforglipron (LY3502970) in participants with type 2 diabetes and inadequate glycemic control with insulin glargine, with or without metformin and/or SGLT-2 inhibitor (ACHIEVE-5). ClinicalTrials.gov identification: NCT06109311. Updated April 17, 2025. Accessed October 16, 2025. https://clinicaltrials.gov/study/NCT06109311?term=NCT06109311&rank=1