Differences in Cardiovascular and Renal Outcomes Between Sodium Glucose Co-Transporter-2 and Dipeptidyl Peptidase-4 Inhibitors Among Type 2 Diabetes Patients: A Real-World, Retrospective Cohort Study

Abstract

Background: Sodium–glucose cotransporter–2 inhibitors (SGLT2i) reduce the risk of cardiovascular or renal disease (CVRD). Dipeptidyl peptidase–4 inhibitors (DPP4i) have not shown these effects. Methods This retrospective cohort study propensity matched 24,438 patients receiving a SGLT2i 1:1 to a person receiving a DDP4i, stratified based on presence of CVRD. Primary outcomes were the time to each of the following: all–cause mortality, cardiovascular death or hospitalisation for heart failure (HF), myocardial infarction, stroke and chronic kidney disease (CKD). Findings: Overall, SGLT2i were associated with reductions in all–cause mortality (hazard ratio 0·73, 95%; confidence interval 0·63–0·84), cardiovascular mortality (0·80, 0·66–0·97), HF hospitalisation (0·74, 0·65–0·84) and CKD hospitalisation (0·51, 0·47–0·56; all p<0·001) compared with DPP4i. In patients with no CVRD history, SGLT2i were associated with reductions in all–cause mortality (0·71, 0·57–0·88; p=0·002), HF hospitalisation (0·76, 0·59–0·98; p=0·035) and CKD hospitalisation (0·75, 0·63–0·88; p<0·001). In patients with established CVD or at high risk, SGLT2i were associated with reductions in all–cause mortality (0·69, 0·59–0·82); p<0·001), cardiovascular mortality (0·76, 0·62–0·95; p=0·014), HF hospitalisation (0·73, 0·63–0·85; p<0·001), stroke hospitalisation (0·75, 0·59–0·94, p=0·013) and CKD hospitalisation (0·49, 0·43–0·54, p<0·001). Results were consistent across subgroups and sensitivity analyses. Interpretation: SGLT2i were associated with reduced risk of all–cause mortality and hospitalisation for HF and CKD compared with DPP4–i, highlighting the need to introduce SGLT2i early in the management of T2D patients. Funding Statement: AstraZeneca. Declaration of Interests: KK has acted as a consultant, speaker or received grants for investigator–initiated studies for Astra Zeneca, Novartis, Novo Nordisk, Sanofi–Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin–Chemie AG / Menarini Group, Janssen, and Napp. II has acted as an advisory board member, speaker or received grants for Eli Lilly, Novo Nordisk, Merck Sharp & Dohme, AstraZeneca, Abbot Diabetes Care, Sanofi, Boehringer. RZ, JBM, MF and TM are employed by AstraZeneca UK Ltd, a biopharmaceutical company who develops, manufactures and markets medicines in the cardiovascular, renal and metabolic disease area. AB has received research grants from Astra Zeneca. Ethics Approval Statement: The study protocol was approved by the Independent Scientific Advisory Committee (ISAC) of CPRD; protocol reference number: 19_231.