Background: Dipeptidyl peptidase-4 inhibitors (DPP-4i) interact with sulfonylureas (SU) to increase their risk of hypoglycemia. However, it is unclear whether this risk varies with the pharmacologic properties of DPP-4i. Thus, we compared the risk of severe hypoglycemia between concomitant use of SU and peptidomimetic DPP-4i (vildagliptin, saxagliptin) vs. non-peptidomimetic DPP-4i (sitagliptin, linagliptin, alogliptin) in patients with type 2 diabetes.
Methods: We conducted a retrospective cohort study using the UK's Clinical Practice Research Datalink linked to hospitalization and vital statistics data of patients with type 2 diabetes initiating SU between 20 and 2020. Time-dependent Cox models estimated hazard ratios (HR) with 95% confidence intervals (CI) of severe hypoglycemia associated with current concomitant use of SU and peptidomimetic DPP-4i compared to current concomitant use of SU and non-peptidomimetic DPP-4i, adjusted for baseline confounders. Secondary analyses stratified by age (<65 vs. ≥65 years) and sex.
Results: Our cohort included 196,138 SU initiators. The crude incidence rate of severe hypoglycemia was 7.2 per 1000/year. Compared to concomitant use of SU and non-peptidomimetic DPP-4i, concomitant use of SU and peptidomimetic DPP-4i was not associated with the risk of severe hypoglycemia (HR, 0.96; 95% CI, 0.76-1.22) . In female patients, concomitant use of SU and peptidomimetic DPP-4i was associated with a trend towards an increased risk (HR, 1.32; 95% CI, 0.97-1.81) ; in male patients, there was an association with a decreased risk (HR, 0.69; 95% CI, 0.48-0.99) . Age did not modify the association.
Conclusion: Our population-based study showed no increased risk of severe hypoglycemia with concomitant use of SU and peptidomimetic DPP-4i compared to concomitant use of SU and non-peptidomimetic DPP-4i. Further research is needed to corroborate the observed effect modification by sex.
J.Dimakos: None. Y.Cui: None. R.W.Platt: Consultant; Amgen Inc., Biogen, Merck & Co., Inc., Nant Pharma, Pfizer Inc. C.Renoux: None. K.B.Filion: None. A.Douros: None.
Canadian Institutes of Health Research (PJT-165882)