Efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus and established cardiovascular disease using insulin: A VERTIS CV substudy

Diabetes Obes Metab. 2021 Jul;23(7):1640-1651. doi: 10.1111/dom.14385. Epub 2021 May 5.

Abstract

Aim: To assess the efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus (T2DM) and established atherosclerotic cardiovascular disease (ASCVD) inadequately controlled by insulin.

Materials and methods: VERTIS CV was the cardiovascular outcome study for ertugliflozin. Patients were randomly assigned to placebo, or ertugliflozin 5 mg or 15 mg once daily. We report the results of a substudy in patients on a stable dose of insulin ≥20 units/d. The primary endpoint was glycated haemoglobin (HbA1c) change from baseline to 18 weeks. Secondary endpoints were changes in fasting plasma glucose (FPG), body weight (BW), the proportion of patients with HbA1c <53 mmol/mol (<7%), systolic blood pressure (SBP), diastolic blood pressure and insulin dose.

Results: Of 8246 patients randomized in VERTIS CV, 1065 were included in the substudy (68.2% men, mean [SD] age 64.8 [7.8] years, T2DM duration 16.7 [9.0] years, HbA1c 8.4 [1.0]%). At week 18, the least squares (LS) mean change from baseline in HbA1c was significantly greater with ertugliflozin 5 mg and 15 mg versus placebo (placebo-adjusted LS mean change -0.58%, 95% confidence interval [CI] -0.71, -0.44 and -0.65%, 95% CI -0.78, -0.51, respectively; P < 0.001 for both). Ertugliflozin significantly reduced FPG, BW and SBP. In women, the incidence of genital mycotic infections was higher with ertugliflozin (3.5%) versus placebo (0.0%). The incidence of symptomatic hypoglycaemia was similar across treatment groups.

Conclusions: Ertugliflozin added to insulin improved glycaemic control, BW and SBP versus placebo at 18 weeks in patients with T2DM and ASCVD.

Trial registration: ClinicalTrials.gov NCT01986881.

Keywords: SGLT2 inhibitor; cardiovascular disease; glycaemic control; insulin therapy; type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose
  • Bridged Bicyclo Compounds, Heterocyclic
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Insulin / therapeutic use
  • Male
  • Metformin* / therapeutic use
  • Middle Aged
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects
  • Treatment Outcome

Substances

  • Blood Glucose
  • Bridged Bicyclo Compounds, Heterocyclic
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Sodium-Glucose Transporter 2 Inhibitors
  • ertugliflozin
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT01986881