Birkeland KI, et al. – A multinational observational analysis was designed to compare cardiovascular mortality and morbidity in new users of sodium–glucose co–transporter–2 (SGLT2) inhibitors versus new users of other glucose–lowering drugs, in a population with a broad cardiovascular risk profile. The data indicated that SGLT2 inhibitor use was associated with reduced cardiovascular disease and cardiovascular mortality compared with use of other glucose–lowering drugs—a finding consistent with the results of clinical trials in patients at high cardiovascular risk in a population of patients with type 2 diabetes and a broad cardiovascular risk profile.

Methods

• CVD-REAL Nordic was an observational analysis of individual patient-level data from the Prescribed Drug Registers, Cause of Death Registers, and National Patient Registers in Denmark, Norway, and Sweden.
• They included all patients who filled a prescription for glucose-lowering drugs between 2012 and 2015 and followed up until Dec 31, 2015.
• They categorized patients into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs.
• In this analysis, each SGLT2 inhibitor user was matched with three users of other glucose-lowering drugs by use of propensity scores.
• They evaluated hazard ratios (HRs) by country (Cox survival model) and weighted averages were calculated.
• In this study, cardiovascular mortality, major adverse cardiovascular events (cardiovascular mortality, myocardial infarction, and ischaemic or haemorrhagic stroke), hospital events for heart failure (inpatient or outpatient visit with a primary diagnosis of heart failure), non-fatal myocardial infarction, non-fatal stroke, and atrial fibrillation were investigated.
• They also evaluated incidence of severe hypoglycaemia.

Results

• At baseline, matched SGLT2 inhibitor (n=22830) and other glucose-lowering drug (n=68490) groups were well balanced, with a mean follow-up of 0•9 (SD 4•1) years (80669 patient-years) and mean age of 61 (12•0) years; 40% (36362 of 91320) were women and prevalence of cardiovascular disease was 25% (22686 of 91320).
• 94% of the total SGLT2 inhibitor exposure time was for use of dapagliflozin, with 5% for empagliflozin, and 1% for canagliflozin.
• It was noted that use of SGLT2 inhibitors was correlated with decreased risk of cardiovascular mortality (HR 0•53 [95% CI 0•40–0•71]), major adverse cardiovascular events (0•78 [0•69–0•87]), and hospital events for heart failure (0•70 [0•61–0•81]; p
• They did not distinguish significant differences between use of SGLT2 inhibitors and use of other glucose-lowering drugs for non-fatal myocardial infarction, non-fatal stroke, or atrial fibrillation.
• When compared with other glucose-lowering drugs, use of SGLT2 inhibitors was correlated with a decreased risk of severe hypoglycaemia (HR 0•76 [0•65–0•90]; p=0•001).
• The differences were similar for the 25% of individuals with cardiovascular disease at baseline and those without (HR 0•60 [0•42–0•85] vs 0•55 [0•34–0•90]) for cardiovascular mortality, although for major adverse cardiovascular events the HR in the group with cardiovascular disease at baseline was 0•70 (0•59-0•83) versus 0•90 (0•76–1•07) in the group without.