(300) Peptidomimetic Structure of Dipeptidyl Peptidase-4 Inhibitors and The Risk of Sulfonylurea-Induced Severe Hypoglycemia: A Population-Based Cohort Study

Friday, August 26, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 631

Presenting Author(s)

Jenny Dimakos
– McGill University, Department of Medicine, Montreal, Quebec, Canada

Co-Author(s)

Ying Cui
– Research Assistant, Centre for Clinical Epidemiology, Lady Davis Institute, Canada
Robert W. Platt, PhD
– Professor, McGill Dept of Epidemiology, Biostatistics and Occupational Health, Montreal, Quebec, Canada
Christel Renoux, MD PhD
– Associate Professor, Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada., Canada
Kristian Filion, PhD
– Associate Professor, McGill University, Montreal, QC, Canada
Antonios Douros, MD, Dr
– Assistant Professor, Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montréal, QC, Canada, McGill University, Montreal, Quebec, Canada

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are antidiabetic drugs that interact with sulfonylureas and increase their risk of hypoglycemia. However, it is unknown whether this risk varies with the pharmacologic properties of DPP-4 inhibitors (peptidomimetic vs non-peptidomimetic).

Objectives: To assess the risk of severe hypoglycemia associated with concomitant use of sulfonylureas with peptidomimetic DPP-4 inhibitors (vildagliptin, saxagliptin) compared with concomitant use of sulfonylureas with non-peptidomimetic DPP-4 inhibitors (sitagliptin, linagliptin, alogliptin) in patients with type 2 diabetes.

Methods: This retrospective cohort study used the United Kingdom’s Clinical Practice Research Datalink linked to hospitalization and vital statistics data. We included patients initiating sulfonylurea treatment between 2007 and 2020. Time-dependent Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of severe hypoglycemia (defined as hospitalization with or death due to hypoglycemia) associated with concomitant use of sulfonylureas with peptidomimetic DPP-4 inhibitors compared to concomitant use of sulfonylureas with non-peptidomimetic DPP-4 inhibitors, adjusted for baseline covariates. We also assessed potential effect measure modifications by age and sex. Sensitivity analyses assessed potential exposure and outcome misclassification.

Results: The study cohort included 196,138 sulfonylurea initiators. Median (interquartile range) follow-up was 6.02 (2.93-9.16) years, during which 8,576 events of severe hypoglycemia occurred (crude incidence rate, 7.17 [95% CI, 7.02 to 7.32] per 1000 person-years). When compared with concomitant use of sulfonylureas with non-peptidomimetic DPP-4 inhibitors, concomitant use of sulfonylureas with peptidomimetic DPP-4 inhibitors was not associated with an increased risk of severe hypoglycemia (HR, 0.96; 95% CI, 0.76 to 1.22). There was effect modification by sex, with concomitant use of sulfonylureas with peptidomimetic DPP-4 inhibitors being associated with a numerically increased risk of severe hypoglycemia among female patients (HR, 1.32; 95% CI, 0.97 to 1.81) and a decreased risk among male patients (HR, 0.69; 95% CI, 0.48 to 0.99; p for heterogeneity = 0.009). Age did not modify the association. Sensitivity analyses yielded findings that were consistent with those of the primary analysis.

Conclusions: Our study showed no increased risk of severe hypoglycemia associated with concomitant use of sulfonylureas and peptidomimetic DPP-4 inhibitors compared with concomitant use of sulfonylureas with non-peptidomimetic DPP-4 inhibitors. Further research is needed to corroborate the observed effect measure modification by sex.