Orforglipron Improved Markers of Beta-Cell Function and Insulin Sensitivity in Type 2 Diabetes

How does Orforglipron (OFG) improve markers of beta-cell function and insulin sensitivity in comparison to Dulaglutide (DULA) in patients with type 2 diabetes (T2D)?

Method: In this 26-week phase 2 study of adults with type 2 diabetes (T2D), we investigated mechanisms by which OFG improved glycemic control in T2D by analyzing exploratory biomarkers. Participants with T2D (mean age, 58.9 years; baseline HbA1c, 8.1%; weight, 100.3 kg) treated with diet and exercise, with/without metformin, were randomized to PBO, DU 1.5 mg, or once-daily OFG 3, 12, 24, 36, or 45 mg. Biomarkers of β-cell function and insulin sensitivity were analyzed by mixed model repeated measures, excluding data after study drug discontinuation or rescue drug initiation.

Results: Biomarkers of β-cell function were improved by OFG at 26 weeks from baseline. HOMA-B significantly increased with OFG at doses≥12 mg vs PBO or DU. HOMA-IR (computed with insulin) significantly decreased from baseline with OFG at doses≥24 mg but was not significantly different vs PBO and DU. Fasting glucose-adjusted glucagon significantly decreased with OFG at doses≥12 mg vs PBO and with OFG 12, 24, and 45 mg vs DU.

Conclusion: These analyses suggest improved glycemic control with OFG vs DU may be partly explained by improved β-cell function and insulin sensitivity. Additional studies are ongoing to understand these mechanisms.

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Artikel online veröffentlicht:
28. Mai 2025