A Long-acting Glucose-dependent Insulinotropic Polypeptide Receptor Agonist Improved Insulin Sensitivity and Beta-Cell Function in Participants with Type 2 Diabetes

What were the effects of LAGIPRA and dulaglutide, both separately and in combination, on insulin sensitivity and beta-cell function in participants with type 2 diabetes?

Methods: In this Phase 1b study, participants with T2D were enrolled in a 12-week randomized, controlled trial to evaluate the effect of LY3532226 (LAGIPRA) 20 mg weekly, dulaglutide 1.5 mg weekly, or LAGIPRA plus dulaglutide weekly on insulin sensitivity and beta-cell function. The effects were assessed by performing hyperinsulinemic euglycemic and hyperglycemic clamps at baseline and after 12 weeks’ treatment. Insulin sensitivity (M-value) and insulin secretion rate (ISR0-120min) were assessed separately and combined into a clamp disposition index (cDI).

Results: LAGIPRA and dulaglutide monotherapy led to modest weight loss and improvement in HbA1c. The effect on weight loss with combination therapy was additive at 12 weeks. LAGIPRA monotherapy modestly augmented insulin secretion responses but showed a 3-fold stronger improvement in insulin sensitivity than dulaglutide monotherapy. The combination showed additive effects on both insulin sensitivity and beta-cell function, and at least additive effects on cDI.

Conclusion: Both LAGIPRA and dulaglutide improved body weight and HbA1c, but their effects on insulin sensitivity and beta-cell function differed. LAGIPRA primarily improved insulin sensitivity, whereas dulaglutide had a greater effect on insulin secretion. These effects on insulin sensitivity and secretion were additive when dulaglutide and LAGIPRA were combined.

Publikationsverlauf

Artikel online veröffentlicht:
28. Mai 2025