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Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: The VERTIS SITA2 placebo-controlled randomized study.

ABSTRACT: AIMS:To assess ertugliflozin in patients with type 2 diabetes who are inadequately controlled by metformin and sitagliptin. MATERIALS AND METHODS:In this double-blind randomized study (Clinicaltrials.gov NCT02036515), patients (glycated haemoglobin [HbA1c] 7.0% to 10.5% [53-91?mmol/mol] receiving metformin ?1500?mg/d and sitagliptin 100?mg/d; estimated glomerular filtration rate [eGFR] ?60?mL/min/1.73?m2 ) were randomized to ertugliflozin 5?mg once-daily, 15?mg once-daily or placebo. The primary efficacy endpoint was change from baseline in HbA1c at Week 26; treatment was continued until Week 52. RESULTS:A total of 464 patients were randomized (mean baseline HbA1c, 8.0% [64.3?mmol/mol]; eGFR, 87.9?mL/min/1.73?m2 ). After 26?weeks, placebo-adjusted least squares (LS) mean changes in HbA1c from baseline were -0.7% (-7.5?mmol/mol) and -0.8% (-8.3?mmol/mol) for ertugliflozin 5 and 15?mg, respectively (both P?

SUBMITTER: Dagogo-Jack S

PROVIDER: S-EPMC5836931 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: The VERTIS SITA2 placebo-controlled randomized study.

Dagogo-Jack Samuel S Liu Jie J Eldor Roy R Amorin Guillermo G Johnson Jeremy J Hille Darcy D Liao Yuqin Y Huyck Susan S Golm Gregory G Terra Steven G SG Mancuso James P JP Engel Samuel S SS Lauring Brett B

Diabetes, obesity & metabolism 20171023 3

<h4>Aims</h4>To assess ertugliflozin in patients with type 2 diabetes who are inadequately controlled by metformin and sitagliptin.<h4>Materials and methods</h4>In this double-blind randomized study (Clinicaltrials.gov NCT02036515), patients (glycated haemoglobin [HbA1c] 7.0% to 10.5% [53-91 mmol/mol] receiving metformin ≥1500 mg/d and sitagliptin 100 mg/d; estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m<sup>2</sup> ) were randomized to ertugliflozin 5 mg once-daily, 15 mg once-dai ...[more]

PMID: 28921862

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Project description:IntroductionThis study assessed the safety and efficacy of ertugliflozin (an oral sodium-glucose cotransporter 2 inhibitor) vs. glimepiride in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin.MethodsThis phase III, double-blind, non-inferiority study (NCT01999218) randomized patients with HbA1c ≥ 7.0% and ≤ 9.0% on stable metformin ≥ 1500 mg/day 1:1:1 to ertugliflozin 15 or 5 mg once-daily (QD), or glimepiride (titrated from 1 mg QD). The primary hypothesis was that ertugliflozin 15 mg was non-inferior to glimepiride on HbA1c (non-inferiority criterion: upper bound of the 95% confidence interval [CI] about the treatment difference < 0.3%).ResultsMean baseline HbA1c of randomized patients (N = 1326) was 7.8%. Mean and median doses of glimepiride were 3.0 mg/day throughout the study. At week 52, the least squares mean change (95% CI) from baseline in HbA1c was - 0.6% (- 0.7, - 0.5), - 0.6% (- 0.6, - 0.5), and - 0.7% (- 0.8, - 0.7) in the ertugliflozin 15 mg, ertugliflozin 5 mg, and glimepiride groups, respectively. The between-group difference for ertugliflozin 15 mg and glimepiride of 0.1% (- 0.0, 0.2) met the pre-specified non-inferiority criterion. Relative to glimepiride, greater body weight and systolic blood pressure (SBP) reductions were observed with ertugliflozin. The overall incidence of adverse events (AEs) was similar across groups. The incidence of symptomatic hypoglycemia and genital mycotic infection (GMI) were, respectively, lower and higher with ertugliflozin relative to glimepiride. The incidences of urinary tract infection and hypovolemia AEs were not meaningfully different among the groups.ConclusionsErtugliflozin 15 mg was non-inferior to glimepiride in reducing HbA1c when added to metformin in patients with T2DM. Ertugliflozin had an acceptable safety profile and resulted in less hypoglycemia and more GMIs than glimepiride.Clinical trial registrationClinicaltrials.gov NCT01999218.

Project description:IntroductionSulfonylureas (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).MethodsThis 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.ResultsAmong 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.ConclusionThe 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 registrationClinicalTrials.gov identifier: NCT01986881.

Project description:IntroductionVERTIS CV is the cardiovascular outcome trial for the sodium-glucose cotransporter 2 (SGLT2) inhibitor ertugliflozin. A sub-study was conducted to assess the efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately glycemic-controlled on metformin and a sulfonylurea (SU).MethodsPatients with T2DM, established atherosclerotic cardiovascular disease (ASCVD), and an HbA1c of 7.0-10.5% on stable metformin (≥ 1500 mg/day) and moderate to high SU doses were randomly assigned to once-daily ertugliflozin (5 or 15 mg) or placebo. The primary sub-study objectives were to assess the effect of ertugliflozin on HbA1c compared with placebo and to evaluate safety following 18 weeks of treatment. Key secondary endpoints included changes in fasting plasma glucose (FPG), body weight (BW), blood pressure (BP), and the proportion of patients achieving HbA1c < 7%.ResultsOf the 8246 patients enrolled in VERTIS CV, 330 were eligible for this sub-study (ertugliflozin 5 mg, n = 100; ertugliflozin 15 mg, n = 113; placebo, n = 117). This subgroup had a mean (SD) age of 63.2 (8.4) years and T2DM duration of 11.4 (7.4) years. At week 18, ertugliflozin 5 mg and 15 mg were each associated with significantly greater least squares (LS) mean reductions from baseline in HbA1c relative to placebo (placebo-adjusted LS mean [95% CI] - 0.66% [- 0.89, - 0.43] and - 0.75% [- 0.98, - 0.53], respectively, p < 0.001 for each dose vs placebo). Ertugliflozin significantly reduced FPG and BW compared with placebo (p < 0.001), but not systolic BP. Adverse events were reported in 48.0%, 54.9%, and 47.0% of patients in the ertugliflozin 5 mg and 15 mg, and placebo groups. The incidences of symptomatic hypoglycemia were 11.0% (5 mg), 12.4% (15 mg), and 7.7% (placebo), and of severe hypoglycemia 2.0% (5 mg), 1.8% (15 mg), and 0.9% (placebo).ConclusionsIn patients with T2DM and ASCVD, ertugliflozin added to metformin and SU improved glycemic control, reduced BW, and was generally well tolerated.Trial registrationVERTIS CV ClinicalTrials.gov identifier, NCT01986881.

Dataset Information

Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: The VERTIS SITA2 placebo-controlled randomized study.

Publications

Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: The VERTIS SITA2 placebo-controlled randomized study.

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