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

Abstract

IntroductionLixisenatide 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).MethodsWe 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).ResultsLixisenatide 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.ConclusionLixisenatide 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.FundingSanofi (China) Investment Co., Ltd., Shanghai, China.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-016-0207-6) contains supplementary material, which is available to authorized users.

Lixisenatide, a Once‐Daily Prandial Glucagon‐Like Peptide‐1 Receptor Agonist for the Treatment of Adults with Type 2 Diabetes

“…22,29,42,43 Two metaanalyses of Asian subpopulations in the GetGoal studies also showed significant reductions versus placebo in Hb A1c levels, FPG levels, and PPG levels at week 24 among patients with poorly controlled glycemia receiving OADs or insulin. 44,45 A post hoc analysis of data from GetGoal-L, GetGoal Duo-1, and GetGoal Duo-2 showed no significant differences in efficacy and safety outcomes for lixisenatide-treated white and Latino/ Hispanic patients. 46…”

“…Greater reductions in 2‐hour PPG levels were observed in Asian patients adding lixisenatide to basal insulin in GetGoal‐L‐Asia compared with patients enrolled in the GetGoal‐L and GetGoal Duo‐1 studies, but no significant differences in weight loss between lixisenatide‐ and placebo‐treated Asian patients were observed in GetGoal‐S, GetGoal‐L‐Asia, or GetGoal‐M‐Asia (Table ) . Two meta‐analyses of Asian subpopulations in the GetGoal studies also showed significant reductions versus placebo in Hb A1c levels, FPG levels, and PPG levels at week 24 among patients with poorly controlled glycemia receiving OADs or insulin …”

“…Typical of the pharmacologic class, the most common adverse events experienced by patients treated with lixisenatide across the phase 3 clinical trials were transient, mild‐to‐moderate gastrointestinal manifestations. The frequency of nausea, which mostly occurred during the first 3–4 weeks of treatment and resolved without intervention, varied from 16.3% to 50.0%; frequencies of vomiting ranged from 2.8% to 18.2% and diarrhea from 3.0% to 12.4% (Table ) …”

“…The frequency of nausea, which mostly occurred during the first 3-4 weeks of treatment and resolved without intervention, varied from 16.3% to 50.0%; frequencies of vomiting ranged from 2.8% to 18.2% and diarrhea from 3.0% to 12.4% (Table 3). [19][20][21][22][23][24][25][26][27][28][29][30][31][32]45 Hypoglycemia, serious adverse events, and discontinuation rates are summarized in Table 3. The incidence of hypoglycemia associated with use of lixisenatide as a single agent was low: 0.8% and 2.5% for patients receiving the drug in oneand two-step dose increase schedules, respectively, in the GetGoal-Mono trial.…”

Network Pharmacology and Traditional Chinese Medicine: Development of Anti-Diabetic Therapies

“…Diabetes mellitus, "xiao-ke" in TCM, is a chronic metabolic disease affecting more than 400 million people worldwide [1]. The onset of diabetes is attributed to a deficiency in insulin secretion or impaired biological activity of insulin.…”