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).

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.

• Authors: Julio Rosenstock, Markolf Hanefeld, Paramesh Shamanna, Kyung Wan Min, Gabor Boka, Patrick Miossec, Tianyue Zhou, Isabel Muehlen-Bartmer, Robert E Ratner
• Journal: Journal of diabetes and its complications (J Diabetes Complications) 2014 May-Jun Vol. 28 Issue 3 Pg. 386-92 ISSN: 1873-460X [Electronic] United States
• PMID: 24650952 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• Adult
• Aged
• Blood Glucose (metabolism)
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Glucagon (blood)
• Glycated Hemoglobin (metabolism)
• Humans
• Hypoglycemia (blood, 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