Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin (GetGoal-F1).

Abstract

AIMS:

To assess the efficacy and safety of one- and two-step dose-increase regimens of lixisenatide once daily in participants with Type 2 diabetes mellitus insufficiently controlled with metformin.

METHODS:

This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre study enrolling participants with Type 2 diabetes (n = 484) treated with metformin. Participants were randomized to receive either lixisenatide in a one-step dose increase or a two-step dose increase vs. placebo for 24 weeks, followed by a ≥ 52-week variable double blind period. Primary outcome was HbA1c reduction at week 24.

RESULTS:

Lixisenatide one-/two-step once daily significantly improved HbA1c at week 24 compared with placebo (P < 0.0001) and allowed more participants to achieve HbA1c < 53 mmol/mol (< 7.0%) (P ≤ 0.0005). Improvements were observed in fasting plasma glucose (-0.5/-0.6 vs. +0.1 mmol/l; P < 0.001) and body weight (-2.6/-2.7 vs. -1.6 kg; P < 0.005). At week 24, adverse events were reported by 67.7/70.8/65.6% of participants treated with lixisenatide one-/two-step/placebo, respectively--nausea and vomiting being reported most frequently. Symptomatic hypoglycaemia occurred in 1.9/2.5% of participants on one-/two-step lixisenatide and 0.6% with placebo, with no severe episodes. Lixisenatide continued to be efficacious and well tolerated during the variable double-blind extension period of at least 52 weeks.

CONCLUSIONS:

Lixisenatide one- or two-step dose-increase regimens significantly improved glycaemic control and decreased body weight over 24 weeks and during a long-term extension period without increasing hypoglycaemia. The study confirmed that tolerability in the one-step group was at least similar to the two-step dose increase, with nausea/vomiting and hypoglycaemia frequency being lower in the one-step regimen.

• Authors: G B Bolli, M Munteanu, S Dotsenko, E Niemoeller, G Boka, Y Wu, M Hanefeld
• Journal: Diabetic medicine : a journal of the British Diabetic Association (Diabet Med) Vol. 31 Issue 2 Pg. 176-84 (Feb 2014) ISSN: 1464-5491 [Electronic] England
• PMID: 24117597 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Chemical References

• Hypoglycemic Agents
• Peptides
• Placebos
• lixisenatide
• Metformin

Topics

• Adult
• Aged
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Drug Administration Schedule
• Female
• Humans
• Hypoglycemic Agents (administration & dosage, adverse effects)
• Male
• Metformin (therapeutic use)
• Middle Aged
• Peptides (administration & dosage, adverse effects)
• Placebos
• Treatment Failure
• Treatment Outcome
• Young Adult