Efficacy and Safety of Ertugliflozin in Patients With Diabetes Mellitus Inadequately Controlled by Sulfonylurea Monotherapy: a Substudy of VERTIS CV

Abstract

Introduction: Sulfonylureas (SU) are commonly used antihyperglycemic agents. VERTIS CV was the cardiovascular outcome study for the sodium-glucose cotransporter 2 inhibitor ertugliflozin. Enrollment of patients in VERTIS CV occurred in two sequential cohorts (Cohort 1 and Cohort 2).

Methods: This substudy assessed the efficacy and safety of adding ertugliflozin to SU monotherapy. The primary endpoint was the change in HbA1c from baseline at 18 weeks.

Results: Among the 8246 patients who were randomized in VERTIS CV, 157 patients in Cohort 1 and 135 patients in Cohort 2 were on SU monotherapy at baseline. In the prespecified analysis (Cohort 1 only), the least squares (LS) mean HbA1c change from baseline for placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg was - 0.56%, - 0.91%, and - 0.78%, respectively (placebo-adjusted LS mean [95% CI] change: - 0.35% [- 0.72%, 0.02%]; - 0.22% [- 0.60%, 0.16%] for ertugliflozin 5 and 15 mg, respectively; p > 0.05 for both). In a post-hoc analysis that included Cohorts 1 and 2 (N = 292), the LS mean HbA1c change from baseline at week 18 for placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg was - 0.31%, - 0.77%, and - 0.68%, respectively (placebo-adjusted change: - 0.46% [- 0.73%, - 0.18%]; - 0.37% [- 0.66%, - 0.09%]; p = 0.001 and 0.01 for ertugliflozin 5 and 15 mg, respectively). In Cohort 1, adverse events were reported in 45.8%, 47.3%, and 25.9% of patients with placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg. The incidence rates of symptomatic hypoglycemia were 0.0%, 5.5%, and 3.7%, respectively, with no cases of severe hypoglycemia. The safety profile was similar for Cohorts 1 and 2 combined.

Conclusion: The addition of ertugliflozin to SU monotherapy reduced HbA1c but did not result in significant placebo-adjusted reductions from baseline according to the prespecified primary analysis (n = 157); however, in a post-hoc analysis with a larger patient population (n = 292), significant and clinically relevant HbA1c reductions were observed. Ertugliflozin was generally well tolerated.

Trial registration: ClinicalTrials.gov identifier: NCT01986881.

Keywords: Glycemic; HbA1c; SGLT2 inhibitor; Secondary prevention; Sodium-glucose cotransporter 2 inhibitor; Type 2 diabetes mellitus.

Fig. 1

Study flow diagram (Cohort 1)

Fig. 2

LS mean change from baseline in HbA1c over time (Cohort 1)

Fig. 3

Efficacy outcomes (Cohort 1): a LS mean change from baseline in HbA1c at week 18; b LS mean change from baseline in FPG at week 18. Efficacy outcomes in the post-hoc analysis (Cohort 1 and Cohort 2 combined); c LS mean change from baseline in HbA1c at week 18; d LS mean change from baseline in FPG at week 18