Comparative effectiveness and safety of sodium‐glucose cotransporter‐2 inhibitors versus metformin in patients with type 2 diabetes: An observational study using data from routine care. Issue 10 (13th July 2021)

• Record Type: Journal Article
• Authors: Fralick, Michael; Schneeweiss, Sebastian; Redelmeier, Donald A.; Razak, Fahad; Gomes, Tara; Patorno, Elisabetta
• Is Part Of: Diabetes, obesity & metabolism. Volume 23:Issue 10(2021)
• Page Start: 2320
• Page End: 2328
• Publication Date: 2021-07-13
• Subjects: antidiabetic drug -- cohort study -- metformin -- SGLT2 inhibitor -- type 2 diabetes; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.14474
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract: Aim: To assess the effectiveness and safety of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors in treatment‐naïve patients compared with metformin. Participants and Methods: We conducted a cohort study of US adults with type 2 diabetes mellitus who had not filled a prescription for a diabetes medication in the preceding year. We then identified patients who newly filled a prescription for an SGLT2 inhibitor or metformin between 2013 and 2018. The primary outcome was a composite of heart failure, myocardial infarction or stroke. Safety outcomes included hypoglycaemia, diabetic ketoacidosis, genital infection, lactic acidosis and acute kidney injury. After 1:1 propensity‐score (PS) matching, proportional hazards models were fit to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results: We identified 9964 individuals newly prescribed an SGLT2 inhibitor who were PS‐matched to 9964 individuals newly prescribed metformin. The mean age was 54 years, 52% were women, and the duration of follow‐up was 213 days for metformin and 147 days for SGLT2 inhibitors. The primary outcome occurred in 54 patients (7.2 events per 1000 person‐years) who received an SGLT2 inhibitor, compared to 84 patients (8.5 per 1000 person‐years) who received metformin (HR 0.82, 95% CI 0.58, 1.15). Similar results (HR 0.87, 95% CI 0.69, 1.09) were observed in an analysis with longer follow‐up (ie, approximately 600 days). The rates of genital infection (HR 2.28, 95% CI 1.87, 2.78) and diabetic ketoacidosis (HR 1.58, 95% CI 0.92, 2.70) were higher for patients prescribed an SGLT2 inhibitor compared to metformin, while the rates of acute kidney injury (HR 0.94, 95% CI 0.60, 1.47) or hypoglycaemia (HR 0.83, 95% CI 0.48, 1.42) were not. Conclusions: We observed a numerically lower rate of short‐/mid‐term cardiovascular events for patients newly prescribed an SGLT2 inhibitor compared to metformin, albeit with wide CIs that include the possibility of a null effect. SGLT2 inhibitors were associated with a higher rate of genital infection and diabetic ketoacidosis. Larger cohort studies and long‐term clinical trials powered to assess cardiovascular events are necessary to understand the risk‐benefit profile of SGLT2 inhibitors as first‐line therapy for adults with type 2 diabetes mellitus.