Risk of HF and Death in Patients on SGLT-2 Inhibitors

Study Questions:

What is the risk for hospitalization for heart failure (HHF), death, and the combined endpoint in patients with type 2 diabetes (T2D) who were new users of the sodium-glucose cotransporter-2 inhibitor (SGLT-2i) versus other glucose-lowering drugs (oGLDs) in real-world practice?


The investigators collected data via medical claims, primary care/hospital records, and national registries from the United States, Norway, Denmark, Sweden, Germany and the United Kingdom. Propensity score for SGLT-2i initiation was used to match treatment groups. Hazard ratios (HRs) for HHF, death, and their combination were estimated by country. The HRs (95% confidence interval [CI]) for each of the endpoints from each individual country were then pooled together for an overall weighted summary, in which random-effects models with inverse variance weighting for each country were implemented. Death data were not available for Germany.


After propensity matching, there were 309,056 patients newly initiated on either SGLT-2i or oGLDs (154,528 patients in each treatment group). Canagliflozin, dapagliflozin, and empagliflozin accounted for 53%, 42%, and 5% of the total exposure time in the SGLT-2i class, respectively. Baseline characteristics were balanced between the two groups. There were 961 HHF cases during 190,164 person-years of follow-up (incidence rate [IR], 0.51/100 person-years). Of 215,622 patients in the United States, Norway, Denmark, Sweden, and United Kingdom, death occurred in 1,334 (IR, 0.87/100 person-years), and HHF or death in 1,983 (IR, 1.38/100 person-years). Use of SGLT-2i, versus oGLDs, was associated with lower rates of HHF (HR, 0.61; 95% CI, 0.51-0.73; p < 0.001); death (HR, 0.49; 95% CI, 0.41-0.57; p < 0.001); and HHF or death (HR, 0.54; 95% CI, 0.48-0.60; p < 0.001) with no significant heterogeneity by country.


The authors concluded that treatment with SGLT-2i versus oGLDs was associated with a lower risk of HHF and death.


This observational study reports that treatment with SGLT-2i versus other glucose-lowering drugs was associated with lower rates of hospitalization for heart failure and death, suggesting that the benefits previously reported with empagliflozin appear to be a class effect. The case for a class effect is further bolstered by the fact that there was significant benefit across countries, despite geographic variations in the use of specific SGLT-2i. Furthermore, the majority of patients did not have known cardiovascular disease, suggesting possible cardiovascular benefits for a broad population of T2D patients in real-world practice.

Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, EP Basic Science, Lipid Metabolism, Acute Heart Failure

Keywords: Benzhydryl Compounds, Diabetes Mellitus, Type 2, Glucose, Glucosides, Heart Failure, Hospitalization, Incidence, Metabolic Syndrome X, Primary Prevention, Risk, Sodium Channels

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