Abstract

BackgroundTo investigate the comparative effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1-RA) on cardiovascular outcomes in routine clinical practice, which have never been directly compared in head-to-head outcome trials. MethodsWe compared outcomes of adults who newly started SGLT2i or GLP1-RA therapy in Stockholm, Sweden, during 2013–2019. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular (CV) death, myocardial infarction and stroke. Secondary outcomes included the individual MACE components and hospitalization for heart failure. Cox regression with propensity score overlap weighting was used to estimate hazard ratios (HRs) with 95% confidence intervals and adjust for 57 covariates. ResultsWe included 12,375 individuals, of which 5489 initiated SGLT2i and 6886 GLP1-RA therapy, followed for median 1.6 years. Mean age was 61 years and 37.6% were women. Compared with GLP1-RA, SGLT2i new users had similar risk of MACE risk (adjusted HR 1.04; 95% CI 0.83–1.31). The adjusted HRs (95% CI) for SGLT2i vs. GLP1-RA were 0.80 (0.59–1.09) for heart failure hospitalization, 0.95 (0.58–1.55) for cardiovascular death, 0.91 (0.67–1.24) for myocardial infarction and 1.71 (1.14–2.59) for ischemic stroke (5-year absolute risk difference for stroke 1.9% [95% CI 0.8–3.0]). ConclusionsIn a largely primary-prevention population of people undergoing routine care, no differences were observed in MACE risk among initiators of SGLT2i and GLP1-RA. However, compared with GLP1RA, the use of SGLT2i was associated with an increased risk of ischemic stroke that was small in absolute magnitude.

Highlights

  • Type 2 diabetes mellitus (T2DM) affects more than 400 million in­ dividuals worldwide [1]

  • The E-value for ischemic stroke was 2.81 for the point estimate and 1.54 for the lower limit of the confidence interval, meaning that an unmea­ sured confounder would need to be associated with both the sodium-glucose cotransporter 2 inhibitors (SGLT2i) initiation and ischemic stroke by a risk ratio of 2.81 to bring the point estimate to 1.0, and a risk ratio of 1.54 to bring the lower confidence limit to 1.0. In this cohort study of individuals from routine clinical practice, we observed no differences in major adverse cardiovascular events (MACE) risk between new users of SGLT2i and glucagon-like peptide 1 receptor agonists (GLP1-RA)

  • We observed a significantly higher risk for ischemic stroke in the SGLT2i group compared with GLP1-RA

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Summary

Introduction

Type 2 diabetes mellitus (T2DM) affects more than 400 million in­ dividuals worldwide [1]. Large cardiovascular outcome trials and their systematic reviews and meta-analyses have shown that both glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 in­ hibitors (SGLT2i) reduce the risk of major adverse cardiovascular events (MACE) in patients with T2DM [4–12]. To investigate the comparative effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1-RA) on cardiovascular outcomes in routine clinical practice, which have never been directly compared in head-to-head outcome trials. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular (CV) death, myocardial infarction and stroke. The adjusted HRs (95% CI) for SGLT2i vs GLP1-RA were 0.80 (0.59–1.09) for heart failure hospitalization, 0.95 (0.58–1.55) for cardiovascular death, 0.91 (0.67–1.24) for myocardial infarction and 1.71 (1.14–2.59) for ischemic stroke (5-year absolute risk dif­ ference for stroke 1.9% [95% CI 0.8–3.0]). Compared with GLP1RA, the use of SGLT2i was associated with an increased risk of ischemic stroke that was small in absolute magnitude

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