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Clinical Trial
. 2020 Jul;22(7):1122-1131.
doi: 10.1111/dom.14011. Epub 2020 Mar 12.

Cardiovascular and renal benefits of dapagliflozin in patients with short and long-standing type 2 diabetes: Analysis from the DECLARE-TIMI 58 trial

Harpreet S Bajaj  1   2 , Itamar Raz  3 , Ofri Mosenzon  3 , Sabina A Murphy  4 , Aliza Rozenberg  3 , Ilan Yanuv  3 , Deepak L Bhatt  4 , Lawrence A Leiter  5 , Darren K McGuire  6 , John P H Wilding  7 , Ingrid A M Gause-Nilsson  8 , Marc S Sabatine  4 , Stephen D Wiviott  4 , Avivit Cahn  3
Affiliations
Clinical Trial

Cardiovascular and renal benefits of dapagliflozin in patients with short and long-standing type 2 diabetes: Analysis from the DECLARE-TIMI 58 trial

Harpreet S Bajaj et al. Diabetes Obes Metab. 2020 Jul.

Abstract

Aim: To investigate whether the cardiovascular and renal benefits observed with dapagliflozin in the DECLARE-TIMI 58 trial are also observed in patients with short and long-standing diabetes.

Materials and methods: This post hoc analysis studied the dual primary efficacy endpoints, a composite of cardiovascular death or hospitalization for heart failure (CVD/HHF) and major adverse cardiovascular events (MACE; CVD, myocardial infarction [MI], ischaemic stroke) by diabetes duration.

Results: Of the 17 160 patients, 3836 had diabetes duration of ≤5 years, 4731 >5-10 years, 3952 >10-15 years, 2433 >15-20 years and 2206 >20 years. Dapagliflozin reduced the risk of CVD/HHF by a similar amount across diabetes duration subgroups, ranging from HR 0.79 (0.58-1.06) in patients with diabetes duration of ≤5 years to 0.75 (0.55-1.03) in those patients with diabetes duration of >20 years (interaction trend P-value 0.76). Hazard ratios (HRs) for MACE ranged from 1.08 (0.87-1.35) in patients with diabetes duration of ≤5 years to 0.67 (0.52-0.86) in those patients with diabetes duration of >20 years (interaction trend P-value 0.004). This was driven by greater reductions in the risk of MI and ischaemic stroke with dapagliflozin in patients with long-standing diabetes (interaction trend P-values 0.019 and 0.015, respectively). The duration-based MACE heterogeneity was apparent in those with or without a history of prior MI and in those with multiple risk factors. The renal-specific outcome was reduced with dapagliflozin with HRs ranging from 0.79 (0.47-1.34) in patients with diabetes duration of ≤5 years to 0.42 (0.25-0.72) in those patients with diabetes duration of >20 years (interaction trend P-value 0.084).

Conclusions: Dapagliflozin reduced the risk of CVD/HHF consistently, regardless of diabetes duration, whereas the treatment effect for MACE differed by duration subgroups, with significant reductions with dapagliflozin in patients with long-standing diabetes.

Keywords: cardiovascular disease, dapagliflozin, diabetes duration, major adverse cardiovascular events, sodium-glucose co-transporter-2 inhibitors, type 2 diabetes.

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