Risk of acute pancreatitis among new users of empagliflozin compared to sulfonylureas in patients with type 2 diabetes: A Post-Authorization Safety Study

Background: Jardiance (empagliflozin), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), improves glycemic control among patients with type 2 diabetes mellitus (T2D) by reducing renal glucose reabsorption. Numerous studies have assessed the association between acute pancreatitis (AP) and glucose-lowering drugs, with varying results.

Objectives: To compare the risk of AP in T2D patients initiating empagliflozin (empa) to new users of sulfonylureas (SUs).

Methods: A non-interventional cohort study was conducted in 2 US claims databases (MarketScan CCAE/MDCR and Optum CDM). Adults (aged ≥18 years) with T2D initiating empa or SU, both on a background of metformin, between 1 August 2014 and the latest data-cut available in MarketScan (30 September 2020) and Optum (31 March 2021) were selected. Patients initiating empa were matched 1:1 to patients initiating SU using propensity scores (PS) and evaluated for occurrence of AP using incidence rates per 1000 person-years (PYs) and 95% confidence intervals (CI). Hazard ratios (HR) and 95% CIs were estimated by Cox proportional hazards regression models.

Results: Across MarketScan and Optum databases, there were 72,661 new users of empa and 422,018 new users of SU, both on a background of MF. Mean age (SD) was 57 (12) years in the empa cohort (58% male) and 60 (13) years in the SU cohort (56% male). Baseline characteristics were generally comparable across databases. Incidence rates of AP in the pooled unmatched cohorts were 10.33 (95% CI 9.32-11.42) and 14.78 (95% CI 14.32-15.24) per 1000 PYs for empa and SU, respectively. After 1:1 PS matching, the groups were well-balanced across the 72,621 matched pairs. Mean age (SD) was 57 (12) years and 58% were male. Incidence rates of AP in the pooled matched cohort were 10.30 (95% CI 9.29-11.39) per 1000 PYs for empa and 11.65 (95% CI 10.59-12.77) per 1000 PYs for SU. Patients newly initiating empagliflozin on a background of MF did not have an increased risk of AP compared with those initiating SU on a background of MF (pooled PS matched HR=0.88 [0.76-1.02]). Multiple sensitivity analyses were conducted across various populations and definitional criteria, with results directionally similar to the main analysis.

Conclusions: Results of this voluntary PASS provide additional evidence that use of empa to treat patients with T2D did not have an increased risk of AP, thereby adding to the well-established safety profile of empa.