HMN 2026: How Orforglipron is beneficial for reducing HbA1c in type 2 diabetes

Orforglipron is beneficial for blood glucose control in individuals with type 2 diabetes using metformin or taking insulin glargine, according to two studies published online June 8 in The Lancet and the JAMA to coincide with the annual meeting of the American Diabetes Association, held from June 5 to 8 in New Orleans.

Michelle Welch, M.D., from Consano Clinical Research in San Antonio, and colleagues conducted a 40-week, phase 3, randomized study at 73 sites involving adults with type 2 diabetes using metformin. Participants were randomly assigned to orforglipron 3 mg, 12 mg, or 36 mg or dapagliflozin 10 mg (240, 241, 241, and 240 participants, respectively). The researchers found that for the treatment regimen estimand, all orforglipron doses were noninferior to dapagliflozin for reducing glycated hemoglobin (HbA1c) at week 40, with change from baseline in mean HbA1c of ?1.23%, ?1.50%, and ?1.56% for orforglipron 3 mg, 12 mg, and 36 mg, respectively, versus ?0.81% for dapagliflozin.

Francesco Giorgino, M.D., from the University of Bari Aldo Moro in Italy, and colleagues conducted a randomized, phase 3 study at 72 sites involving adults with type 2 diabetes taking insulin glargine with or without metformin and/or sodium-glucose cotransporter 2 inhibitors over 40 weeks. Participants were randomly assigned to receive 3-, 12-, or 36-mg doses of orforglipron or placebo (137, 132, 136, and 141 individuals, respectively) in addition to titrated insulin glargine. The researchers found that the mean changes from baseline in HbA1c were ?1.58%, ?1.88%, and ?1.82% with orforglipron 3, 12, and 36 mg once daily, respectively, compared with ?0.79% with placebo at week 40.

“ACHIEVE-5 results are encouraging because they suggest a once-daily oral GLP-1 option like orforglipron could help improve blood glucose control for people with type 2 diabetes who are already managing complex treatment routines, including basal insulin,” Giorgino said in a statement.

Several authors from both studies disclosed ties to biopharmaceutical companies, including Eli Lilly, which funded the studies and provided the study drug in the Giorgino study.

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