The Separate and Combined Effects of Long-term GIP and GLP-1 Receptor Activation in Patients with Type 2 Diabetes
Summary
Due to reports of a severely reduced insulinotropic effect of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) in type 2 diabetes (T2D), GIP has not been considered therapeutically viable in T2D. Recently, however, tirzepatide, a novel dual incretin receptor agonist (activating both the GIP receptor and the glucagon-like peptide 1 (GLP-1) receptor) demonstrated massive improvements in glycaemic control and robust body weight losses; greater than observed with the GLP-1 receptor agonist semaglutide. However, the contribution of GIP receptor activation to these effects remains unknown. The present study will evaluate the glucose-lowering effect of GIP in the context of pharmacological GLP-1 receptor activation in patients with T2D.
Timeline
- Start
- 2022-01-27
- Primary completion
- 2025-01-06
- Completion
- 2025-01-24
Outcome
Missed primary endpoint
paper 0·80 mmol/L (97·5% CI -0·18 to 1·80; p=0·13 in the placebo plus GIP vs placebo plus placebo groups) PMID 42173109 ↗
paper 6 weeks of subcutaneous GIP infusion as add-on to placebo or semaglutide did not improve glycaemic control in individuals with type 2 diabetes at the prespecified target of 1·50 mmol/L. PMID 42173109 ↗
Publications
- Helsted MM, Fonnesbech-Wulff C, Schaltz NL, Lund IW, Forman JL, Nielsen CK, Englund A, Hartmann B, Vilsboll T, Holst JJ, Lund AB, Christensen MB, Knop FK, Gasbjerg LS. Effects of a 6-week subcutaneous infusion of native GIP alone or as add-on to semaglutide in people with type 2 diabetes: a single-centre, double-blind, parallel-group, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2026 Jul;14(7):581-593. doi: 10.1016/S2213-8587(26)00075-6. Epub 2026 May 22.
- Helsted MM, Gasbjerg LS, Vilsboll T, Nielsen CK, Forman JL, Christensen MB, Knop FK. Separate and combined effects of long-term GIP and GLP-1 receptor activation in patients with type 2 diabetes: a structured summary of a study protocol for a double-blind, randomised, placebo-controlled clinical trial. BMJ Open. 2023 Feb 27;13(2):e065736. doi: 10.1136/bmjopen-2022-065736.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Glucose-dependent insulinotropic polypeptide (GIP) | Unknown | 16 unknown | Subcutaneous |
| Subject | Semaglutide | Peptide | 0.5 mg | Subcutaneous |