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),☆☆

https://doi.org/10.1016/j.jdiacomp.2014.01.012Get rights and content
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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.

Keywords

GLP-1 receptor agonists
Lixisenatide
Sulfonylurea
Type 2 diabetes

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Clinical trial number: NCT00713830. GLP-1 Agonist AVE0010 in patients with type 2 diabetes for glycemic control and safety evaluation, on top of sulfonylurea (GETGOAL S). Registry: clinicaltrials.gov.

Conflicts of interest statement: JR has served on scientific advisory boards and received honoraria or consulting fees or grants/research support from insulin and GLP-1 receptor agonist manufacturers, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, Roche, and Amylin. MH has received speaker honoraria from Roche, Bayer, Lilly, Takeda, GlaxoSmithKline, and Sanofi-Aventis, and advisory board honoraria from Takeda, Bristol-Myers Squibb, Sanofi-Aventis, and GlaxoSmithKline. PS has no competing interests to declare. KWM has received speaker honoraria from Sanofi-Aventis and Takeda. GB, PM, TZ, and IM-B are employees of Sanofi. RER has received research support from Amylin, Boehringer Ingelheim, GlaxoSmithKline, Merck, Novo Nordisk, Pfizer, Roche, Sanofi-Aventis, and Takeda, and has acted as a consultant for Amylin, Eli Lilly, Novo Nordisk, Roche, Sanofi-Aventis, and Takeda.

☆☆

Previous presentations: These data were presented in part as posters at the 47th European Association for the Study of Diabetes (EASD) Annual Meeting, Lisbon, Portugal, 12–16 September 2011, and the World Diabetes Congress of the International Diabetes Federation (IDF), Dubai, UAE, 4–8 September 2011.