Effect of ertugliflozin on blood pressure in patients with type 2 diabetes mellitus: a post hoc pooled analysis of randomized controlled trials

Abstract

BackgroundThe efficacy of ertugliflozin, a sodium–glucose cotransporter 2 inhibitor, for glycemic and blood pressure (BP) control has been demonstrated in phase 3 studies. To further evaluate the effects of ertugliflozin on BP and other hemodynamic parameters, an analysis was conducted on the pooled patient populations from these studies.MethodsThis was a post hoc analysis of data from three phase 3 studies (NCT01958671, NCT02033889, and NCT02036515) of adults with type 2 diabetes mellitus who received placebo, ertugliflozin 5\xa0mg, or ertugliflozin 15\xa0mg. Outcomes at 26\xa0weeks were analyzed for the pooled population and according to relevant baseline factors, including BP.ResultsOf the 1544 patients included (placebo, n\u2009=\u2009515; ertugliflozin 5\xa0mg, n\u2009=\u2009519; ertugliflozin 15\xa0mg, n\u2009=\u2009510), most (67.4–69.0%) had hypertension at baseline. Mean baseline BP was similar across treatment groups (placebo, 129.7/78.0\xa0mmHg; ertugliflozin 5\xa0mg, 131.0/78.4\xa0mmHg; ertugliflozin 15\xa0mg, 130.5/78.4\xa0mmHg). At Week 26, placebo-adjusted least squares (LS) mean changes (95% confidence intervals [CI]) from baseline in systolic BP (SBP) were −\u20093.7\xa0mmHg (−\u20095.1, −\u20092.3) for both ertugliflozin doses. Reductions were consistent across all baseline subgroups. At Week 26, more patients with a baseline SBP\u2009≥\u2009130\xa0mmHg had a SBP\u2009<\u2009130\xa0mmHg with ertugliflozin (38.7% both doses) than with placebo (24.0%), and more patients with a baseline SBP\u2009≥\u2009140\xa0mmHg attained a SBP\u2009<\u2009140\xa0mmHg with ertugliflozin (59.5% [5\xa0mg] and 66.7% [15\xa0mg]) than with placebo (43.8%). Placebo-adjusted LS mean changes (95% CI) in diastolic BP (DBP) with ertugliflozin 5\xa0mg and 15\xa0mg were −\u20091.8\xa0mmHg (−\u20092.7, −\u20090.9) and −\u20091.6\xa0mmHg (−\u20092.5,\u2009−\u2009\u20090.7), respectively, and in pulse rate were −\u20091.3 beats per minute (bpm) (−\u20092.2, −\u20090.3) and −\u20091.5\xa0bpm (−\u20092.5, −\u20090.6), respectively. Greater reductions in pulse pressure, mean arterial pressure, and double product were observed with ertugliflozin than with placebo. Incidence of adverse event-related osmotic diuresis was low, but greater with ertugliflozin (2.9% [5\xa0mg], 2.4% [15\xa0mg]) than placebo (1.0%).ConclusionErtugliflozin treatment led to reductions in SBP, DBP, and pulse rate relative to placebo. Reductions in SBP were generally consistent across the subgroups evaluated.Trial registration NCT01958671; NCT02033889; NCT02036515