Context: Low dose sulphonylureas have been found to augment the classical incretin effect, increase glucose sensitivity and late phase incretin potentiation.
Objective: To evaluate potential synergy between low dose sulphonylurea plus DPP4 inhibitor.
Design: Unblinded randomised crossover study.
Setting: Clinical Research Centre, University of Dundee.
Participants: 30 participants with T2DM (HbA1c < 64 mmol/mol) treated with diet or metformin.
Intervention: Participants completed four, 14-day blocks in a random order: control, gliclazide 20 mg (SU), sitagliptin 100 mg (DPP4i), or combination (SUDPP4i). A mixed meal test was conducted after each intervention.
Main outcome measure: The primary outcome was the effect of treatment on beta-cell glucose sensitivity. Secondary outcomes included frequency of glucose <3 mmol/l on continuous glucose monitoring, sub-analyses by genotype (KNCJ11 E23 K), gender and body mass index.
Results: SU combination with DPP4i showed additive effect on glucose lowering: Mean glucose AUC (mean 95% CI) (mmol/l) was: Control 11.5 (10.7-12.3), DPP4i 10.2 (9.4-11.1), SU 9.7 (8.9-10.5), SUDPP4i 8.7 (7.9-9.5) (p < 0.001). Glucose sensitivity mirrored the additive effect (pmol min-1 m-2mM-1): Control 71.5 (51.1-91.9), DPP4i 75.9 (55.7-96.0), SU 86.3 (66.1-106.4), SUDPP4i 94.1 (73.9-114.3) (p = 0.04). The additive effect was seen in men but not women. Glucose time in range <3 mmol/l on CGM (%) was unaffected: Control 1 (2-4), DPP4i 2 (3-6), SU 1 (0-4), SUDPP4i 3 (2-7) (p = 0.65).
Conclusions: Low dose sulphonylurea plus DPP4i has potent glucose lowering effect through augmentation of beta cell function. A double-blind randomised controlled trial would formalise efficacy and safety of this combination, which may avoid negative aspects of SU.
Keywords: Beta Cell Function; DPP4 inhibitors; Gliclazide; KATP Channel; Sulphonylureas; Type 2 Diabetes.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.