Dapagliflozin and cardiovascular mortality and disease outcomes in a population with type 2 diabetes similar to that of the DECLARE‐TIMI 58 trial: A nationwide observational study

Abstract

Aims To investigate cardiovascular (CV) safety and event rates for dapagliflozin versus other glucose‐lowering drugs (GLDs) in a real‐world type 2 diabetes population after applying the main inclusion criteria and outcomes from the DECLARE‐TIMI 58 study. Methods Patients with new initiation of dapagliflozin and/or other GLDs were identified in Swedish nationwide healthcare registries for the period 2013 to 2016. Patients were included if they met the main DECLARE‐TIMI 58 inclusion criteria: age ≥40 years and established CV disease or presence of multiple‐risk factors, e.g. men aged ≥55 years and women aged ≥60 years with hypertension or dyslipidaemia. Propensity scores for the likelihood of dapagliflozin initiation were calculated, then 1:3 matching was carried out. DECLARE‐TIMI 58 outcomes were hospitalization for heart failure (HHF) or CV‐specific mortality, and major adverse CV events (MACE; CV‐specific mortality, myocardial infarction, or stroke). Cox survival models were used to estimate hazard ratios (HRs). Results After matching, a total of 28 408 new‐users of dapagliflozin and/or other GLDs were identified, forming the population for the present study (henceforth referred to as the DECLARE‐like cohort. The mean age of this cohort was 66 years, and 34% had established CV disease. Dapagliflozin was associated with 21% lower risk of HHF or CV mortality versus other GLDs (HR 0.79, 95% confidence interval [CI] 0.69‐0.92) and had no significant association with MACE (HR 0.90, 95% CI 0.79‐1.03). HHF and CV mortality risks, separately, were lower at HR 0.79 (95% CI 0.67‐0.93) and HR 0.75 (95% CI 0.57‐0.97), respectively. Non‐significant associations were seen for myocardial infarction and stroke: HR 0.91 (95% CI 0.74‐1.11) and HR 1.06 (95% CI 0.87‐1.30), respectively. Conclusion In a real‐world population similar to those included in the DECLARE‐TIMI 58 study, dapagliflozin was safe with regard to CV outcomes and resulted in lower event rates of HHF and CV mortality versus other GLDs.

Dapagliflozin vs non‐SGLT‐2i treatment is associated with lower healthcare costs in type 2 diabetes patients similar to participants in the DECLARE‐TIMI 58 trial: A nationwide observational study

“…In this nationwide, observational, real‐world study, a novel approach was used to evaluate the estimated total healthcare costs for patients with T2D who initiated treatment with either dapagliflozin or a non‐SGLT‐2i oGLD in a population with a patient profile to similar to that of the DECLARE‐TIMI 58 trial . This DECLARE‐like population, defined by applying the main eligibility criteria from the DECLARE‐TIMI 58 trial to a real‐world population, has been described previously …”

“…Unlike cost‐effectiveness analyses, the analysis reported here does not include a measure of the outcomes, for example, Quality Adjusted Life Years (QALYs). However, as previously shown in a DECLARE‐like population, treatment with dapagliflozin has beneficial CV effects compared with treatment with oGLDs, and this would lead to a QALY benefit. When considered along with this QALY benefit, the cost neutrality between dapagliflozin and oGLDs observed in this study indicates that dapagliflozin is cost‐effective compared with oGLDs.…”

“…This representativeness was two‐ to four‐fold greater than that of other SGLT‐2i CVOTs . Secondly, assessment of the external validity of the results of the DECLARE‐TIMI 58 trial demonstrated that the beneficial CV effects of dapagliflozin could be translated into a real‐world population with T2D . Differences in CV mortality benefits have been shown between CVOTs and observational studies, and this is may be explained by differences in the frailty of the patients included.…”

“…Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor (SGLT-2i) that has been shown to be safe and to effectively reduce CV disease in both high-and low-CV-risk patients in clinical trial and real-world settings. 7,[10][11][12][13][14][15][16] In addition, dapagliflozin is increasingly prescribed worldwide 10,17 and has been observed to be effective in reducing blood glucose levels in various clinical settings. [18][19][20][21][22][23][24][25][26][27] The DECLARE-TIMI 58 trial (ClinicalTrials.gov NCT01730534) 28 was the largest CV outcomes trial (CVOT) concerning an SGLT-2i to date (dapagliflozin, n = 17 160) and applied broad eligibility criteria, resulting in a study population with established CV disease or with multiple CV risk factors.…”

Importance of intensive blood pressure control in type 2 diabetes: Mechanisms, treatments and current guidelines

“…The availability of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors confirmed the role of impaired tubulo‐glomerular balance in the constitution of diabetic kidney disease and hypervolaemia (which favours heart failure in patients with diabetes). In the EMPA‐REG OUTCOME study and in subsequent outcome studies of similar drugs (canagliflozin and dapagliflozin), SGLT2 inhibitors prevented albuminuria and renal failure. Glomerular filtration rate (GFR) dropped initially, and then flattened, as preglomerular resistance was reduced .…”