Insulin Sensitivity and Beta Cell Function With Macupatide Alone or With Dulaglutide in Type 2 Diabetes: A Phase 1b, Randomised Controlled Trial
Authors' conclusion
These findings demonstrate that chronic GIP receptor activation in individuals with T2D leads primarily to increased insulin sensitivity, and that combining GIP and GLP-1 receptor agonism can augment both insulin secretion and insulin sensitivity compared to GLP-1 therapy alone.
Study context
- Population
- People with T2D on metformin
- Comparison
- Macupatide vs dulaglutide vs macupatide plus dulaglutide
Methodological detailsPhase 1b, double-blind
- Phase 1b
- Double-blind
Primary result
As reported in the abstract
Increase in clamp disposition index (cDI), M value (insulin sensitivity) and insulin secretion rate (ISR) from hyperinsulinemic euglycaemic clamps · 12 weeks
- Baseline overall mean clamp disposition index (cDI) (pmol*m-2*L*min-2*kg-1)
- 0.3
- Baseline overall mean M value (mg*kg-1*min-1)
- 5.8
- Baseline overall mean insulin secretion rate (ISR) (pmol*min-1*m-2)
- 116.8
- cDI increase, Macupatide
- 0.2 (63.2% change)
- cDI increase, Dulaglutide
- 0.5 (181.0%)
- cDI increase, Combination
- 1.0 (321.5%)
- M value increase, Macupatide
- 1.3 (33.1%)
- M value increase, Dulaglutide
- 0.2 (10.4%)
- M value increase, Combination
- 2.0 (38.3%)
- ISR increase, Macupatide
- 37.6 (32.2%)
- ISR increase, Dulaglutide
- 191.1 (163.6%)
- ISR increase, Combination
- 225.3 (192.9%)
Safety
Adverse events
- Deaths
- 0
- Most frequent AEs: injection site reactions and diarrhoea
- Discontinuations due to treatment-emergent AEs uncommon
Original publication
Insulin Sensitivity and Beta Cell Function With Macupatide Alone or With Dulaglutide in Type 2 Diabetes: A Phase 1b, Randomised Controlled Trial. Diabetes Obes Metab. Published 2 June 2026. doi:10.
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