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Diabet Med. 2010 Sep;27(9):1024-32. doi: 10.1111/j.1464-5491.2010.03020.x.

Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial.

Collaborators (134)

Chacra A, Dias MA, Dinato M, Eliaschewitz F, Ellinger V, Forti A, Godoy A, Gomes M, Halpern A, Hissa M, Lerario AC, Macedo G, Manenti E, Oliveira JE, Pedrosa H, Rassi N, Repetto G, Salles J, Sgarbi JA, Ruy Lyra da Silva F, Suplicy H, Tschiedel B, Vargas R, Zanella M, Aronson R, Cha J, Goldenberg R, Hudson N, Kamouna M, Klassen L, Kooy J, MacKinnon R, Misik K, O'Mahony M, Skamene A, Twum-Barima Y, Wade A, Woo V, Konieczny M, Kuleta J, Laskawiec G, Mader P, Pieniazek A, Szolkiewicz M, Szymczyk I, Zytkiewicz-Jaruga D, Barnea A, Busegeanu M, Crisan C, Lichiardopol R, Mindrescu N, Morosanu M, Pop L, Stamoran M, Szilagyi I, Barbarash O, Chernova N, Chumakova G, Raskina T, Zonova E, Botsyurko V, Katerenchuk V, Mankovsky B, Pertseva T, Serhiyenko A, Vlasenko M, Abernethy J, Ahmann AJ, Arakaki RF, Baliga S, Bartkowiak AJ Jr, Bernstein BR, Blair-Britt L, Bolognese M, Busch RS, Buynak R, Byrd LJ, Cardona DW, Chappel CM, Christensen RB, Cohen L, Copeland TN, Corder C, Crabtree Y, Dwarakanathan A, Donovan DS, Jackson Downey H, Evans RM, Eyzaguirre R, Goldberg RB, Goldstein BJ, Gollapudi GM, Gottschlich GM, Guice M, Handelsman Y, Hartman I, Hoekstra JA, Hollander P, Jackson RL, Jasper D, Kalafer M, Kaye WA, Koehler LR, Lender D, Lodewick P, Lovell CF, Lucas KJ, Lyons TJ, Marcelli M, Miers W, Miller SS, Norwood PS, Ovalle F, Peters PJ, Phillips F, Riveland BR, Rizvi SW, Rosenstock J, Schumacher DR, Schwartz SL, Schwartz RB, Scott CL, Shah AJ, Shandilya L, Shomali M, Siddiqqi MI, Soule J, Strzinek R, Sugimoto D, Underberg J, Wade TA, Wittmer BA, Zamora BM, Zisser HC.

Author information

1
Medstar Research Institute and Georgetown University Medical School, Washington, DC, USA.

Abstract

AIMS:

To evaluate the dose-response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes.

METHODS:

Randomized, double-blind, placebo-controlled, parallel-group, 13 week study of 542 patients with Type 2 diabetes inadequately controlled [glycated haemoglobin (HbA(1c)) > or = 7.0 and < 9.0% (> or = 53 and < 75 mmol/mol)] on metformin (> or = 1000 mg/day) treated with subcutaneous lixisenatide doses of 5, 10, 20 or 30 microg once daily or twice daily or placebo. The primary end-point was change in HbA(1c) from baseline to 13 weeks in the intent-to-treat population.

RESULTS:

Lixisenatide significantly improved mean HbA(1c) from a baseline of 7.55% (59.0 mmol/mol); respective mean reductions for 5, 10, 20 and 30 microg doses were 0.47, 0.50, 0.69 and 0.76% (5.1, 5.5, 7.5 and 8.3 mmol/mol), on once-daily and 0.65, 0.78, 0.75 and 0.87% (7.1, 8.5, 8.2 and 9.5 mmol/mol) on twice-daily administrations vs. 0.18% (2.0 mmol/mol) with placebo (all P < 0.01 vs. placebo). Target HbA(1c) < 7.0% (53 mmol/mol) at study end was achieved in 68% of patients receiving 20 and 30 microg once-daily lixisenatide vs. 32% receiving placebo (P < 0.0001). Dose-dependent improvements were observed for fasting, postprandial and average self-monitored seven-point blood glucose levels. Weight changes ranged from -2.0 to -3.9 kg with lixisenatide vs. -1.9 kg with placebo. The most frequent adverse event was mild-to-moderate nausea.

CONCLUSIONS:

Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin. Dose-response relationships were seen for once- and twice-daily regimens, with similar efficacy levels, with a 20 microg once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio. This new, once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies.

PMID:
20722676
PMCID:
PMC3068287
DOI:
10.1111/j.1464-5491.2010.03020.x
[Indexed for MEDLINE]
Free PMC Article

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