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

Abstract

Background: The 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.

Methods: This 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 mg, or ertugliflozin 15 mg. Outcomes at 26 weeks were analyzed for the pooled population and according to relevant baseline factors, including BP.

Results: Of the 1544 patients included (placebo, n = 515; ertugliflozin 5 mg, n = 519; ertugliflozin 15 mg, n = 510), most (67.4-69.0%) had hypertension at baseline. Mean baseline BP was similar across treatment groups (placebo, 129.7/78.0 mmHg; ertugliflozin 5 mg, 131.0/78.4 mmHg; ertugliflozin 15 mg, 130.5/78.4 mmHg). At Week 26, placebo-adjusted least squares (LS) mean changes (95% confidence intervals [CI]) from baseline in systolic BP (SBP) were - 3.7 mmHg (- 5.1, - 2.3) for both ertugliflozin doses. Reductions were consistent across all baseline subgroups. At Week 26, more patients with a baseline SBP ≥ 130 mmHg had a SBP < 130 mmHg with ertugliflozin (38.7% both doses) than with placebo (24.0%), and more patients with a baseline SBP ≥ 140 mmHg attained a SBP < 140 mmHg with ertugliflozin (59.5% [5 mg] and 66.7% [15 mg]) than with placebo (43.8%). Placebo-adjusted LS mean changes (95% CI) in diastolic BP (DBP) with ertugliflozin 5 mg and 15 mg were - 1.8 mmHg (- 2.7, - 0.9) and - 1.6 mmHg (- 2.5, - 0.7), respectively, and in pulse rate were - 1.3 beats per minute (bpm) (- 2.2, - 0.3) and - 1.5 bpm (- 2.5, - 0.6), 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 mg], 2.4% [15 mg]) than placebo (1.0%).

Conclusion: Ertugliflozin 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.

Keywords: Blood pressure; Diastolic blood pressure; Ertugliflozin; Hypertension; Pulse rate; Sodium–glucose cotransporter 2 inhibitor; Systolic blood pressure; Type 2 diabetes mellitus.

Conflict of interest statement

J.L. and A.P are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. They may own stock in Merck & Co., Inc., Kenilworth, NJ, USA.

S.G., A.D., and S.G.T are employees and shareholders of Pfizer Inc.

Figures

Fig. 1

Change from baseline in systolic blood pressure (SBP). Change from baseline in SBP at Week 26 (a) and proportion of patients with SBP < 130 mmHg and < 140 mmHg at Week 26 (b). CI confidence interval; LS least squares. *Placebo-adjusted difference in LS mean (95% CI). †Of patients with baseline SBP of ≥ 130 mmHg. ‡Of patients with baseline SBP of ≥ 140 mmHg. §Difference in response rate (95% CI)

Fig. 2

Change from baseline in systolic blood pressure (SBP) by baseline SBP and antihypertensive therapy use. Change from baseline in SBP at Week 26 by baseline SBP level (a) and baseline antihypertensive therapy, diuretics, and renin–angiotensin–aldosterone system (RAAS) blocker use (b). CI confidence interval; LS least squares. *Placebo-adjusted difference in LS mean (95% CI). †Mean baseline SBP across groups was 126–127 or 132–133 mmHg in patients with or without baseline antihypertensive therapy, respectively

Fig. 3

Estimate of difference from baseline in systolic blood pressure (SBP) at Week 26 by subgroup. Data are presented as n1, n2, and n3 where n1 = number of patients in the placebo group, n2 = number of patients in the ertugliflozin 5 mg group, and n3 = number of patients in the ertugliflozin 15 mg group. BMI body mass index, eGFR estimated glomerular filtration rate, HbA1c glycated hemoglobin

Fig. 4

Correlation between systolic blood pressure (SBP) and glycated hemoglobin (HbA1c) and body weight. Change from baseline in SBP at Week 26 versus change from baseline in HbA1c at Week 26 (a) and change from baseline in body weight at Week 26 (b). HbA1c glycated hemoglobin

Fig. 5

Change from baseline in sitting diastolic blood pressure (DBP) and pulse rate at Week 26. Change from baseline in sitting DBP at Week 26 (a) and change from baseline in sitting pulse rate at Week 26 (b). CI confidence interval, LS least squares. *Placebo-adjusted difference in LS mean (95% CI)