Dataset Information

Lixisenatide Improves Glycemic Control in Asian Type 2 Diabetic Patients Inadequately Controlled With Oral Antidiabetic Drugs: An Individual Patient Data Meta-Analysis.

ABSTRACT:

Introduction

Lixisenatide is a novel GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus (T2DM). Its efficacy and safety have been assessed in a series of phase 3 studies included in the GetGoal program. In these studies, lixisenatide was found to be superior to placebo in glycemic control. The aim of this meta-analysis was to assess the safety and efficacy of lixisenatide as an adjunct therapy in Asian patients with T2DM in adequately controlled with oral antidiabetic drugs (OADs).

Methods

We performed a meta-analysis from five lixisenatide phase 3 studies. In each of these multiethnic studies, patients with T2DM inadequately controlled (glycated hemoglobin, HbA1c ≥7%) with established OADs were randomized to lixisenatide or placebo for 24 weeks, with a balanced distribution of Asian patients in these two arms (503 and 338 patients in the intent-to-treat population, respectively).

Results

Lixisenatide was superior to placebo in reducing HbA1c (weighted, total mean difference -0.57%; P = 0.002). More patients treated with lixisenatide versus placebo achieved HbA1c targets of ≤7% (49.1% vs. 28.4%, P = 0.003). Lixisenatide was superior to placebo in lowering 2-h postprandial glucose (PPG) (weighted, total mean difference -5.50 mmol/l, P = 0.0005). More patients treated with lixisenatide versus placebo achieved 2-h PPG targets of ≤7.8 mmol/l (39.2% vs. 2.2%, P < 0.0001). More patients treated with lixisenatide versus placebo achieved both an HbA1c target of ≤7% and a 2-h PPG target of ≤10 mmol/l (34.8% vs. 2.69%, P < 0.00001). The body weight of the lixisenatide group tended to decrease. Lixisenatide was generally well tolerated.

Conclusion

Lixisenatide as an adjunct therapy can significantly improve the glycemic control of Asian patients with type 2 DM who do not meet targets for glycemic control with an established OAD regimen.

Funding

Sanofi (China) Investment Co., Ltd., Shanghai, China.

SUBMITTER: Shu H

PROVIDER: S-EPMC5118245 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThe aim of this study was to compare the efficacy, safety and cost-utility (from the Chinese health insurance perspective) of lixisenatide and insulin regimens in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on oral antidiabetic drugs (OADs).MethodsA comprehensive literature search of English (PubMed and Cochrane Library) and Chinese (CNKI and WanFang) language databases was performed, and head-to-head relevant randomized controlled trials (RCTs) were retrieved and analyzed by performing a mixed-treatment comparison (MTC) meta-analysis for efficacy and safety endpoints. A cost-utility analysis was then conducted using the IQVIA CORE Diabetes Model to compare the lifetime pharmacoeconomic profiles among the treatment groups.ResultsEleven RCTs were included in this MTC meta-analysis. Regarding glycated hemoglobin targets, lixisenatide was similar to both basal insulin (mean difference [MD] 0.27%; 95% credible interval [CrI] 0.02%, 0.57%) and premixed insulin (MD 0.32%; 95% CrI - 0.01%, 0.66%), respectively. Statistically significant differences were found for changes in body weight in favor of lixisenatide compared with basal insulin (MD - 3.22 kg; 95% CrI - 5.51 kg, - 0.94 kg) and premixed insulin (MD - 2.68 kg; 95% CrI - 5.16 kg, - 0.20 kg). The relative risk (RR) of symptomatic hypoglycemia associated with lixisenatide was also significantly lower than that associated with basal insulin (RR 0.22; 95% CrI 0.09, 0.52) and premixed insulin (RR 0.17; 95% CrI 0.07, 0.41). The cost-utility analysis yielded results of ¥61,072 ($8565, vs. basal insulin) and ¥127,169 ($17,836, vs. premixed insulin) per quality-adjusted life year gained, with both values falling within the willingness-to-pay threshold in China.ConclusionsFor T2DM patients inadequately controlled on OADs, lixisenatide was shown to be comparable to basal insulin and premixed insulin in terms of HbA1c and better than both of the latter in terms of both body weight loss and hypoglycemia. Lixisenatide was also a cost-effective treatment option from the perspective of Chinese health insurance.

Project description:INTRODUCTION:This study aimed to demonstrate the beneficial effect of lixisenatide as add-on therapy to oral antidiabetics (OADs) in type 2 diabetes mellitus (T2DM) patients in routine clinical practice in Bulgaria. METHODS:This was a prospective, observational, multicentre study evaluating the real-life effectiveness and safety of 24-week treatment with lixisenatide in previously uncontrolled T2DM patients on combination therapy with metformin and sulfonylurea on highest tolerable doses. RESULTS:A total of 262 patients were included in the study. The mean (± SD) age in the cohort was 56.2 ± 9.1 years. The mean duration of diabetes was 7.3 ± 6.0 years. The mean body mass index (BMI) was 39.7 ± 4.7 kg/m2. The mean glycated haemoglobin (HbA1c) at baseline was 8.8 ± 1.1%. The mean fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) at baseline were 10.5 ± 3.1 mmol/L and 12.1 ± 3.4 mmol/L respectively. The proportion of patients achieving HbA1c < 7% at study end was 39.0% (95% CI 32.9-45.3). The proportion of patients reaching their individual HbA1c target was 49.0% (95% CI 42.6-55.4). The mean change in HbA1c from baseline was - 1.3 ± 1.2%. The mean change in FPG was - 2.4 ± 3.0 mmol/L and the mean change in PPG was - 3.2 ± 3.6 mmol/L. The mean body weight change from baseline was - 7.2 ± 5.5 kg. The mean BMI change was - 2.6 ± 1.9 kg/m2. The hypoglycaemia incidence was low: 6.1% for all hypoglycaemic events, 3.8% for symptomatic events and 0.4% for severe events. CONCLUSIONS:Lixisenatide as add-on therapy to OADs in a real-life setting led to significant improvements in glycaemic control with low incidence of hypoglycaemia and beneficial weight loss. Lixisenatide was well tolerated with few patients having adverse events or discontinuing therapy. These findings are consistent with lixisenatide's safety and efficacy profile established in randomized controlled trials (RCTs). FUNDING:Sanofi Bulgaria.

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