Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S)

J Diabetes Complications. May-Jun 2014;28(3):386-92. doi: 10.1016/j.jdiacomp.2014.01.012. Epub 2014 Jan 28.

Abstract

Aims: To assess efficacy and safety of lixisenatide once-daily versus placebo in type 2 diabetes mellitus (T2DM) patients inadequately controlled on sulfonylurea (SU) ± metformin.

Methods: In this randomized, double-blind, two-arm, parallel-group, multicenter study, patients received lixisenatide 20 μg once-daily or placebo for 24 weeks in a stepwise dose increase on top of SUs ± metformin. Primary outcome was change in HbA1c from baseline to Week 24.

Results: Lixisenatide provided a significant reduction in HbA1c at Week 24 versus placebo (LS mean: -0.85% vs. -0.10%; p<0.0001) and more patients achieved HbA1c <7.0% (36.4% vs. 13.5%; p<0.0001). Lixisenatide significantly lowered FPG and body weight versus placebo. In breakfast meal test patients, lixisenatide reduced 2-hour PPG versus placebo (LS mean: -111.48 vs. -3.80 mg/dL [-6.19 vs. -0.21 mmol/L]; p<0.0001) and glucose excursion (-94.11 vs. +6.24 mg/dL [-5.22 vs. +0.35 mmol/L]), and reduced 2-hour glucagon, insulin, proinsulin, and C-peptide. The percentage of AEs was 68.3% for lixisenatide and 61.1% for placebo; and for SAEs: 3.5% versus 5.6%, respectively. Lixisenatide did not significantly increase symptomatic hypoglycemia versus placebo (15.3% vs. 12.3%, respectively); one severe episode of hypoglycemia was reported with lixisenatide.

Conclusions: Once-daily lixisenatide significantly improved glycemic control, with a pronounced postprandial effect, without significant increase in symptomatic/severe hypoglycemia risk and with weight loss over 24 weeks.

Trial registration: ClinicalTrials.gov NCT00713830.

Keywords: GLP-1 receptor agonists; Lixisenatide; Sulfonylurea; Type 2 diabetes.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glucagon / blood
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / prevention & control*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood
  • Internationality
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Peptides / therapeutic use*
  • Postprandial Period*
  • Sulfonylurea Compounds / therapeutic use*
  • Treatment Outcome

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Peptides
  • Sulfonylurea Compounds
  • lixisenatide
  • Glucagon
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT00713830