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

Cardiovasc Diabetol. 2019 May 7;18(1):59. doi: 10.1186/s12933-019-0856-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects*
  • Bridged Bicyclo Compounds, Heterocyclic / adverse effects
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Heart Rate / drug effects
  • Humans
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Biomarkers
  • Blood Glucose
  • Bridged Bicyclo Compounds, Heterocyclic
  • Sodium-Glucose Transporter 2 Inhibitors
  • ertugliflozin

Associated data

  • ClinicalTrials.gov/NCT01958671
  • ClinicalTrials.gov/NCT02033889
  • ClinicalTrials.gov/NCT02036515