Dapagliflozin is associated with lower risk of cardiovascular events and all‐cause mortality in people with type 2 diabetes (CVD‐REAL Nordic) when compared with dipeptidyl peptidase‐4 inhibitor therapy: A multinational observational study

Abstract

AimsTo compare the sodium‐glucose‐cotransporter‐2 (SGLT‐2) inhibitor dapagliflozin with dipeptidyl peptidase‐4 (DPP‐4) inhibitors with regard to risk associations with major adverse cardiovascular (CV) events (MACE; non‐fatal myocardial infarction, non‐fatal stroke or cardiovascular mortality), hospitalization for heart failure (HHF), atrial fibrillation and severe hypoglycaemia in patients with type 2 diabetes (T2D) in a real‐world setting.MethodsAll patients with T2D prescribed glucose‐lowering drugs (GLDs) during 2012 to 2015 were identified in nationwide registries in Denmark, Norway and Sweden. Patients were divided into two groups: new users of dapagliflozin and new users of DPP‐4 inhibitors, matched 1:3 by propensity score, calculated by patient characteristics, comorbidities and drug treatment. Cox survival models were used to estimate hazard ratio (HR) per country separately, and a weighted average was calculated.ResultsAfter matching, a total of 40 908 patients with T2D were identified as new users of dapagliflozin (n = 10 227) or a DPP‐4 inhibitor (n = 30 681). The groups were well balanced at baseline; their mean age was 61 years and 23% had CV disease. The mean follow‐up time was 0.95 years, with a total of 38 760 patient‐years. Dapagliflozin was associated with a lower risk of MACE, HHF and all‐cause mortality compared with DPP‐4 inhibitors: HRs 0.79 (95% confidence interval [CI] 0.67‐0.94), 0.62 (95% CI 0.50‐0.77), and 0.59 (95% CI 0.49‐0.72), respectively. Numerically lower, but non‐significant HRs were observed for myocardial infarction (0.91 [95% CI 0.72‐1.16]), stroke (0.79 [95% CI 0.61‐1.03]) and CV mortality (0.76 [95% CI 0.53‐1.08]) Neutral associations with atrial fibrillation and severe hypoglycaemia were observed.ConclusionsDapagliflozin was associated with lower risks of CV events and all‐cause mortality compared with DPP‐4 inhibitors in a real‐world clinical setting and a broad T2D population.

How representative of a general type 2 diabetes population are patients included in cardiovascular outcome trials with SGLT2 inhibitors? A large European observational study

“…With consistent evidence of the beneficial effects of SGLT‐2is on CV risk and their strengthened position in guidelines, it is of high importance to understand the actual patient profiles in these CVOTs and, thereby, how representative of a general T2D population the included patient populations actually are . From the present analysis, it is clear that the main inclusion criteria, determining the baseline CV risk in the respective CVOT, are closely correlated to how representative of a general T2D population the trials are in comparison with each other.…”

“…Both Norway and Sweden have comprehensive, nationwide public health care systems (Online Supplemental Appendix 1.3–S14) . All citizens have a unique personal identification number (PIN), which is mandatory for all administrative purposes, including any contact with the health‐care system, as well as drug purchases, thus providing a comprehensive medical history of the population.…”

Observational research on sodium glucose co‐transporter‐2 inhibitors: A real breakthrough?

“…The CVD‐REAL Nordic was the only study examining CV mortality, which was also reduced independently of CV disease at baseline. A further sub‐analysis of the CVD‐REAL Nordic database found that patients newly initiated on dapagliflozin experienced a lower rate of CV events, HHF and all‐cause mortality compared with patients newly initiated on DPP4 inhibitors 12. It appears that the CV benefit was mainly driven by Danish data, whereas the Norwegian cohort was not associated with statistically significant reduction of CV mortality and MACE.…”

Different patterns of second‐line treatment in type 2 diabetes after metformin monotherapy in Denmark, Finland, Norway and Sweden (D360 Nordic): A multinational observational study

“…[2][3][4][5][6][7][8] Moreover, large observational studies have recently shown associations with increased risk of severe hypoglycaemia, CV and all-cause mortality with older GLDs (sulphonylureas and insulins) in second-line treatment. [2][3][4][5][6][7][8] Moreover, large observational studies have recently shown associations with increased risk of severe hypoglycaemia, CV and all-cause mortality with older GLDs (sulphonylureas and insulins) in second-line treatment.…”