Dataset Information

Efficacy and safety of lixisenatide in Japanese patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin: Subanalysis of GetGoal-S.

ABSTRACT:

Aims/introduction

This was a subanalysis of Japanese patients included in the glucagon-like peptide-1 receptor agonist AVE0010 in patients with type 2 diabetes mellitus for glycemic control and safety evaluation (GetGoal-S) study - a 24-week, randomized, placebo-controlled study of lixisenatide in patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin.

Materials and methods

In GetGoal-S, 127 Japanese patients received the once-daily prandial glucagon-like peptide-1 receptor agonist lixisenatide 20 μg/day or a matching placebo. The primary outcome was change in glycated hemoglobin.

Results

At week 24, lixisenatide significantly reduced mean glycated hemoglobin (least squares mean difference vs the placebo -1.1% [12 mmol/mol, P < 0.0001]), and significantly more lixisenatide patients reached glycated hemoglobin targets of <7% (53 mmol/mol) and ≤6.5% (48 mmol/mol) vs the placebo. Lixisenatide produced statistically significant reductions in 2-h postprandial plasma glucose (least squares mean difference vs the placebo -8.51 mmol/L, P < 0.0001) and glucose excursion vs the placebo, and significantly reduced fasting plasma glucose (least squares mean difference vs the placebo -0.65 mmol/L, P = 0.0454). Bodyweight decreased with both lixisenatide and the placebo (least squares mean change -1.12 kg for lixisenatide, -1.02 kg for placebo). The overall incidence of adverse events was similar for lixisenatide and the placebo (84.2 and 82.4%, respectively), the most frequent being gastrointestinal disorders (52.6% for lixisenatide vs 29.4% for placebo). The incidence of symptomatic hypoglycemia was higher with lixisenatide vs the placebo (17.1 and 9.8%, respectively), with no cases of severe symptomatic hypoglycemia in either group.

Conclusions

In the Japanese subpopulation of the GetGoal-S study, lixisenatide produced a significant and clinically relevant improvement in glycated hemoglobin, with a pronounced improvement in postprandial plasma glucose, and a good safety and tolerability profile.

SUBMITTER: Onishi Y

PROVIDER: S-EPMC4364855 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and safety of lixisenatide in Japanese patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin: Subanalysis of GetGoal-S.

Onishi Yukiko Y Niemoeller Elisabeth E Ikeda Yukio Y Takagi Hiroki H Yabe Daisuke D Seino Yutaka Y

Journal of diabetes investigation 20140924 2

<h4>Aims/introduction</h4>This was a subanalysis of Japanese patients included in the glucagon-like peptide-1 receptor agonist AVE0010 in patients with type 2 diabetes mellitus for glycemic control and safety evaluation (GetGoal-S) study - a 24-week, randomized, placebo-controlled study of lixisenatide in patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin.<h4>Materials and methods</h4>In GetGoal-S, 127 Japanese patients received the once-dail ...[more]

PMID: 25802728

Similar Datasets

Project description:ObjectiveTo examine the efficacy and safety of lixisenatide (20 μg once daily, administered before the morning or evening meal) as add-on therapy in patients with type 2 diabetes insufficiently controlled with metformin alone.Research design and methodsThis was a 24-week, randomized, double-blind, placebo-controlled study in 680 patients with inadequately controlled type 2 diabetes (HbA1c 7-10% [53-86 mmol/mol]). Patients were randomized to lixisenatide morning (n = 255), lixisenatide evening (n = 255), placebo morning (n = 85), or placebo evening (n = 85) injections.ResultsLixisenatide morning injection significantly reduced mean HbA1c versus combined placebo (mean change -0.9% [9.8 mmol/mol] vs. -0.4% [4.4 mmol/mol]; least squares [LS] mean difference vs. placebo -0.5% [5.5 mmol/mol], P < 0.0001). HbA1c was significantly reduced by lixisenatide evening injection (mean change -0.8% [8.7 mmol/mol] vs. -0.4% [4.4 mmol/mol]; LS mean difference -0.4% [4.4 mmol/mol], P < 0.0001). Lixisenatide morning injection significantly reduced 2-h postprandial glucose versus morning placebo (mean change -5.9 vs. -1.4 mmol/L; LS mean difference -4.5 mmol/L, P < 0.0001). LS mean difference in fasting plasma glucose was significant in both morning (-0.9 mmol/L, P < 0.0001) and evening (-0.6 mmol/L, P = 0.0046) groups versus placebo. Mean body weight decreased to a similar extent in all groups. Rates of adverse events were 69.4% in both lixisenatide groups and 60.0% in the placebo group. Rates for nausea and vomiting were 22.7 and 9.4% for lixisenatide morning and 21.2 and 13.3% for lixisenatide evening versus 7.6 and 2.9% for placebo, respectively. Symptomatic hypoglycemia occurred in 6, 13, and 1 patient for lixisenatide morning, evening, and placebo, respectively, with no severe episodes.ConclusionsIn patients with type 2 diabetes inadequately controlled on metformin, lixisenatide 20 μg once daily administered in the morning or evening significantly improved glycemic control, with a pronounced postprandial effect, and was well tolerated.

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 lixisenatide in Japanese patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin: Subanalysis of GetGoal-S.

Aims/introduction

Materials and methods

Results

Conclusions

Publications

Efficacy and safety of lixisenatide in Japanese patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin: Subanalysis of GetGoal-S.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets