Long‐term efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: 104‐week VERTIS MET trial

Abstract

Aim To evaluate the long‐term efficacy and safety of ertugliflozin in adults with type 2 diabetes mellitus inadequately controlled on metformin. Materials and Methods A 104‐week Phase III, randomized double‐blind study with a 26‐week placebo‐controlled period (Phase A) and a 78‐week period (Phase B) where blinded glimepiride was added to non‐rescued placebo participants with fasting fingerstick glucose ≥6.1 mmol/L. Results through week 104 are reported. Results Mean (standard error) change in HbA1c from baseline was −0.7% (0.07) and −1.0% (0.07) at week 52; −0.6% (0.08) and −0.9% (0.08) at week 104 for ertugliflozin 5 and 15 mg. At week 52, 34.8% and 36.6% participants had HbA1c <7.0%, and 24.6% and 33.7% at week 104, for ertugliflozin 5 and 15 mg. Ertugliflozin reduced fasting plasma glucose (FPG), body weight and systolic blood pressure (SBP) from baseline through week 104. The incidence of female genital mycotic infections (GMIs) was higher with ertugliflozin, and symptomatic hypoglycaemia was lower for ertugliflozin versus placebo/glimepiride. Minimal bone mineral density (BMD) changes were observed, similar to placebo/glimepiride, except at total hip where reduction in BMD was greater with ertugliflozin 15 mg versus placebo/glimepiride: difference in least squares means (95% CI) –0.50% (−0.95, −0.04) at week 52 and −0.84% (−1.44, −0.24) at week 104. Conclusions Ertugliflozin maintained improvements from baseline in HbA1c, FPG, body weight and SBP through week 104. Ertugliflozin was well tolerated, with non‐clinically relevant changes in BMD. Compared with placebo/glimepiride, ertugliflozin increased female GMIs, but reduced the incidence of symptomatic hypoglycaemia. http://ClinicalTrials.gov Identifier: NCT02033889.

Effects of ertugliflozin on renal function over 104 weeks of treatment: a post hoc analysis of two randomised controlled trials

“…Informed consent was obtained from individuals in each study. The designs for the two studies have been previously published [21][22][23][24] and are summarised in ESM Table 1. Both studies had two treatment phases and a treatment period of 104 weeks.…”

“…In Phase B, participants who had a fasting capillary glucose ≥6.1 mmol/l and were not rescued during Phase A had the addition of blinded glimepiride (for participants randomised to placebo) or glimepiride placebo (for participants randomised to ertugliflozin). Overall, 621 participants were randomised at the start of the study (209, 207 and 205 patients in the placebo, ertugliflozin 5 mg and ertugliflozin 15 mg groups, respectively), and 581 participants entered Phase B (190, 201 and 190 participants in the glimepiride, ertugliflozin 5 mg and ertugliflozin 15 mg groups, respectively) and received ≥1 dose of study medication in Phase B [21]. The VERTIS SU study comprised a double-blind, active-controlled, 52 week treatment period (Phase A), with a double-blind, activecontrolled 52 week treatment extension period (Phase B; ESM Fig.…”

“…Accordingly, in this post hoc, exploratory analysis, we used data from two RCTs (VERTIS MET [ClinicalTrials.gov registration no. NCT02033889] and VERTIS SU [NCT01999218]) that evaluated ertugliflozin vs glimepiride or placebo/glimepiride (non-ertugliflozin) in patients with type 2 diabetes mellitus [21,22], as described in the electronic supplementary material (ESM) Table 1 and ESM Figs 1 and 2. These studies were combined for the purposes of this analysis as they included patients with similar background glucoselowering medication, had the same study duration of 104 weeks and used glimepiride as the active comparator.…”

Effects of dapagliflozin on cardiovascular outcomes in type 2 diabetes

“…This current research is a double blinded, randomized, and prospective trial to determine the influences of the dapagliflozin on the cardiovascular results of type 2 diabetes. [ 24 , 25 ] We assumed that adding the dapagliflozin to the medication in the type 2 diabetes patients would reduce CVD risk and achieve the goal of glycemic control. [ 26 , 27 ]…”

Bioequivalence of Ertugliflozin/Metformin Fixed‐Dose Combination Tablets and Coadministration of Respective Strengths of Individual Components

“…18 Coadministration of ertugliflozin and metformin in a phase 1 study showed that there were no changes in pharmacokinetics (PK) compared with either agent administered alone. 9 The 2 agents have also been coadministered in phase 3 trials, 12,13,[19][20][21] and ertugliflozin given on a background of metformin was well toler-ated and reduced A 1C , fasting plasma glucose, body weight, and blood pressure compared with metformin alone. 12 Fixed-dose combination (FDC) formulations of ertugliflozin plus immediate-release metformin are available, with tablets containing ertugliflozin/metformin 2.5 mg/500 mg, 2.5 mg/1000 mg, 7.5 mg/500 mg, and 7.5 mg/1000 mg (in the United States) or 2.5 mg/850 mg, 2.5 mg/1000 mg, 7.5 mg/850 mg, and 7.5 mg/1000 mg (in the European Union).…”