Association between sodium glucose co-transporter 2 inhibitors and a reduced risk of heart failure in patients with type 2 diabetes mellitus: a real-world nationwide population-based cohort study

Abstract

BackgroundRecently, two large randomized controlled trials which only included patients with underlying cardiovascular disease (CVD) or patients at high risk for CVD showed that two sodium glucose co-transporter 2 inhibitors (SGLT-2is) significantly reduced hospitalization for heart failure (hHF), with an early separation in the survival curves for hHF. There were concerns whether SGLT-2i use could protect hHF in patients without CVD and how soon SGLT-2i-treated patients show a lower risk of hHF. Thus, we aimed to evaluate whether the heart failure protective effect of SGLT-2i differs depending on the underlying CVD and the prescription period compared with dipeptidyl peptidase-4 inhibitors (DPP-4i).MethodsWe performed a nationwide retrospective observational study to estimate the effect of SGLT-2i on HF. The 59,479 SGLT-2i new-users were matched with same number of DPP-4i new-users through propensity score matching using 53 confounding variables. Kaplan–Meier (K–M) curves and Cox proportional hazards regression analyses were used to estimate the risk of hospitalization for hHF.ResultsThe incidence rates of hHF were 0.83 and 1.13 per 100 person-years in SGLT-2i-treated patients and DPP-4i-treated patients, respectively. The hazard ratios of hHF were 0.66 (95% confidence interval 0.58–0.75) in SGLT-2i-treated patients compared with the DPP-4i-treated patients. Among the patients with underlying CVD, SGLT-2i-treated patients were associated with a lower risk of hHF from 30 days to 3 years after initiating drugs compared with DPP-4i. However, SGLT-2i use only showed a lower risk of hHF with a significant difference 3 years after drug initiation among patients without underlying CVD.ConclusionsOur findings suggest that SGLT-2i reduced hHF compared with DPP-4i. A heart failure protective effect of SGLT-2i use vs. DPP-4i use was shown 30 days after initiating the SGLT-2i among patients with established CVD, but this effect appeared later in patients without established CVD.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0737-5) contains supplementary material, which is available to authorized users.

Cardiovascular risks associated with dipeptidyl peptidase‐4 inhibitors monotherapy compared with other antidiabetes drugs in the Japanese population: A nationwide cohort study

“…The risk of HF was also examined by comparison with results from previous studies. 15,16,24 Lastly, we…”

“…Our results on the risks of MI and HF support previous findings from observational studies, which showed that the risk of MI or HF for patients given DPP‐4Is was significantly higher than for those taking BGs but lower than those taking SUs. Ou et al showed that DPP‐4Is were associated with increased risk of MI and HF.…”

“…Nonetheless, the results of sensitivity analysis, in which clinical outcome with mortality was used as a definition of censoring, were consistent with primary analysis. The risk of HF was also examined by comparison with results from previous studies . Lastly, we only focused on DPP‐4Is as monotherapy and could not investigate the effect of individual DPP‐4Is or combination therapy with other drugs.…”

“…Typically, clinical trials cannot consider situations in clinical practice, such as changes in antidiabetic drugs, and the number of enrolled patients is limited. There are several observational studies assessing risks to Asian patients . However, there is no nationwide study in Japan.…”

“…13 In an observational study, 14 There are several observational studies assessing risks to Asian patients. 8,10,[15][16][17] However, there is no nationwide study in Japan.…”