Lower risk of hospitalization for heart failure, kidney disease and death with sodium-glucose co-transporter-2 inhibitors compared with dipeptidyl peptidase-4 inhibitors in type 2 diabetes regardless of prior cardiovascular or kidney disease: A retrospective cohort study in UK primary care

Abstract

Aim: To assess if sodium-glucose co-transporter-2 inhibitors (SGLT2is) reduce the risk of all-cause mortality, cardiovascular death and hospitalization for heart failure (HF) or chronic kidney disease (CKD) to a greater extent than dipeptidyl peptidase-4 inhibitors (DPP4is) in people with type 2 diabetes (T2D) with or without established cardiovascular and/or renal disease (CVRD).

Methods: This retrospective cohort study propensity-matched 24 438 patients receiving an SGLT2i 1:1 to a patient receiving a DDP4i, stratified based on the presence of CVRD. The primary outcomes were the time to each of the following: all-cause mortality, cardiovascular death or hospitalization for HF, myocardial infarction, stroke and CKD.

Results: Overall, SGLT2is were associated with reductions in all-cause mortality, cardiovascular mortality, hospitalization for HF and hospitalization for CKD compared with DPP4is. In patients with no CVRD history, SGLT2is were associated with reductions in all-cause mortality (HR 0.71, 95% CI 0.57-0.88; P = .002), hospitalization for HF (HR 0.76, 95% CI 0.59-0.98; P = .035) and hospitalization for CKD (HR 0.75, 95% CI 0.63-0.88; P < .001). In patients with established cardiovascular disease (CVD) or at high risk, SGLT2is were associated with reductions in all-cause mortality (HR 0.69, 95% CI 0.59-0.82; P < .001), cardiovascular mortality (HR 0.76, 95% CI 0.62-0.95; P = .014), hospitalization for HF (HR 0.73, 95% CI 0.63-0.85; P < .001), hospitalization for stroke (HR 0.75, 95% CI 0.59-0.94; P = .013) and hospitalization for CKD (HR 0.49, 95% CI 0.43-0.54; P < .001).

Conclusion: There was consistency across subgroups and sensitivity analyses. SGLT2is were associated with a reduced risk of all-cause mortality and hospitalization for HF and CKD compared with DPP4-is, highlighting the need to introduce SGLT2is early in the management of patients with T2D.

Keywords: cardiovascular disease; clinical trial; dapagliflozin; diabetes complications; dipeptidyl peptidase-4 inhibitor; heart failure.

FIGURE 1

Patient disposition. CKD, chronic kidney disease; CVD, cardiovascular disease; CVRD, cardiovascular and/or renal disease; DPP4i, dipeptidyl peptidase‐4 inhibitor; GD, gestational diabetes; HF, heart failure; MI, myocardial infarction; PAD, peripheral artery disease; Rx, prescribed; SGLT2i, sodium‐glucose co‐transporter‐2 inhibitor; TZD, thiazolidinedione; T1D, type 1 diabetes; T2D, type 2 diabetes

FIGURE 2

Risk of cardiovascular and renal disease in patients with type 2 diabetes (T2D) without a history of cardiovascular or renal disease and those at high risk of cardiorenal disease (DECLARE‐like). Adjusted Cox regression model with estimates of relative risk reduction. P value is from the test statistic for testing for difference in sodium‐glucose co‐transporter‐2 inhibitors (SGLT2is) versus dipeptidyl peptidase‐4 inhibitors (DPP4is). CKD, chronic kidney disease; CVRD, cardiovascular or renal disease; PY, person years