![]() ![]() This trial thus establishes the CV safety profile of dapagliflozin for use in patients with DM2. The upper limit of the 95% CI for the HR had to be <1.8 for premarketing studies and <1.3 for postmarketing studies. AF/AFL was not a prespecified endpoint, had no central adjudication, and was determined from the MedDRA database, and thus, dependent on the fidelity of reporting.įollowing the much-publicized CV safety concerns with rosiglitazone, the FDA mandated that all new diabetes drugs conduct studies demonstrating CV safety. The effect on atrial arrhythmias is hypothesis generating and should be tested in prospective trials. These drugs reduce hyperglycemia in patients with DM2 by reducing renal glucose reabsorption and thus increasing urinary glucose excretion. These are important findings, and more or less consistent with findings noted with other selective inhibitor of sodium–glucose cotransporter 2 (SGLT-2) inhibitors. Unlike canagliflozin, there was no clear safety signal regarding increased amputations. Effect and safety of CV events was similar irrespective of baseline eGFR and albuminuria. However, in a hypothesis-generating analysis, obese patients (BMI ≥30) had a greater reduction in HF events compared with their nonobese counterparts. The effect of dapagliflozin was consistent across BMI categories. Among patients with HFrEF, dapagliflozin reduced HF hospitalizations, and CV and all-cause mortality however, this cohort comprised only about 4% of the total population. These findings were noted irrespective of baseline BP. There was a reduction in BP, HF hospitalizations, and also a salutary effect on renal outcomes. The results of this trial indicate that dapagliflozin is superior to placebo in improving glycemic control and noninferior but not superior for reducing MACE in patients with DM2 and high CV risk. not, dapagliflozin showed a greater reduction in CV death/HF hospitalization compared with placebo (p for interaction = 0.02) and HF hospitalization (p for interaction = 0.02) among obese patients. No differences in safety were observed based on BMI either. The effect of dapagliflozin compared with placebo was consistent across BMI categories for CV death/HF hospitalization (p for interaction = 0.33), HF hospitalization (p for interaction = 0.20), renal-specific composite outcome (p for interaction = 0.90), and AF/AFL (p for interaction = 0.97). Patients with higher BMI had a higher risk of HF hospitalization and AF/AFL. The beneficial effects of dapagliflozin on HF hospitalization and renal outcomes were consistent across all baseline SBP categories, with no evidence of modification of treatment effect (p-interactions = 0.28 and 0.52, respectively), including among patients with baseline normotension.Įffect of obesity: Of 17,134 patients, 31.5% were overweight, 32.4% were moderately (BMI 30-<35 kg/m 2), 17.2% severely (BMI 35-<40), and 9.8% were very severely (BMI ≥40) obese. Reductions in SBP with dapagliflozin remained sustained at 48 months of follow-up (least means square difference -2.4 mm Hg, 95% CI -2.9 to -1.9, p < 0.0001). 0.7 for eGFR <60, 60-<90 and ≥90, p for interaction < 0.001).Įffects on blood pressure (BP) and baseline hypertension: Effects of dapagliflozin on systolic BP (SBP) were apparent as early as at the first 6 months of trial assessment (least means square difference -3.1 mm Hg, 95% CI -3.5 to -2.7, p < 0.0001). At 6 months, HbA1c reduction was lowest among patients with lower baseline eGFR (least squares mean difference -0.39 vs. Relative and absolute risk reduction was similar for the MACE endpoint. Absolute risk difference with dapagliflozin was highest among the subgroup with two markers of CKD (-8.3% vs. placebo was similar across the three subgroups (p for interaction = 0.24). Relative risk for CV death and HF hospitalization for dapagliflozin vs. Patients with more markers of CKD were more likely to be older, male, and have atherosclerotic CVD and HF at baseline. Patients were categorized as having no more than chronic kidney disease (CKD) stage 2 (65.1%), at least one marker of CKD (31.7%), or both (3.3%). >40% decrease in GFR, end-stage renal disease, or death due to renal or CV causes: 4.3% vs. ![]() The primary outcome of major adverse cardiac events (MACE) for dapagliflozin vs. Chronic cystitis and/or recurrent urinary tract infections.History of bladder cancer or history of radiation therapy to the lower abdomen or pelvis at any time.Established CVD or multiple risk factors including men ≥55 years or women ≥60 years with hypertension, dyslipidemia, or tobacco use.Glomerular filtration rate (GFR) of >60.Glycosylated hemoglobin (HbA1c) of ≥6.5% and ≤12%.Patients were randomized in a 1:1 fashion to either dapagliflozin 10 mg (n = 8,582) or matching placebo (n = 8,578). ![]()
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