Improved Glycemic Control With No Weight Increase in Patients With Type 2 Diabetes After Once-Daily Treatment With the Long-Acting Glucagon-Like Peptide 1 Analog Liraglutide (NN2211)
A 12-week, double-blind, randomized, controlled trial
- Sten Madsbad, MD, DMSC1,
- Ole Schmitz, MD, DMSC2,
- Jonas Ranstam, PHD3,
- Grethe Jakobsen, MSCPHARM3,
- David R. Matthews, DPHIL, FRCP4 and
- on behalf of the NN2211-1310 International Study Group
- 1Hvidovre Hospital, University of Copenhagen, Denmark
- 2University Hospital of Aarhus, Aarhus, Denmark
- 3Novo Nordisk A/S, Bagsvaerd, Denmark
- 4Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, U.K
- Address correspondence and reprint requests to Dr. Sten Madsbad, Department of Endocrinology, Hvidovre Hospital, Kettegaards Allé 30, DK-2650, Hvidovre, Denmark. E-mail: sten.madsbad{at}hh.hosp.dk
Abstract
OBJECTIVE—Liraglutide is a long-acting glucagon-like peptide 1 analog designed for once daily injection. This study assessed the efficacy and safety of liraglutide after 12 weeks of treatment in type 2 diabetic patients.
RESEARCH DESIGN AND METHODS—A double-blind, randomized, parallel-group, placebo-controlled trial with an open-label comparator arm was conducted among 193 outpatients with type 2 diabetes. The mean age was 56.6 years and the mean HbA1c was 7.6% across the treatment groups. Patients were randomly assigned to one of five fixed-dosage groups of liraglutide (0.045, 0.225, 0.45, 0.60, or 0.75 mg), placebo, or open-label sulfonylurea (glimepiride, 1–4 mg). The primary end point was HbA1c after 12 weeks; secondary end points were fasting serum glucose, fasting C-peptide, fasting glucagon, fasting insulin, β-cell function, body weight, adverse events, and hypoglycemic episodes.
RESULTS—A total of 190 patients were included in the intention-to-treat (ITT) analysis. HbA1c decreased in all but the lowest liraglutide dosage group. In the 0.75-mg liraglutide group, HbA1c decreased by 0.75 percentage points (P < 0.0001) and fasting glucose decreased by 1.8 mmol/l (P = 0.0003) compared with placebo. Improvement in glycemic control was evident after 1 week. Body weight decreased by 1.2 kg in the 0.45-mg liraglutide group (P = 0.0184) compared with placebo. The proinsulin-to-insulin ratio decreased in the 0.75-mg liraglutide group (−0.18; P = 0.0244) compared with placebo. Patients treated with glimepiride had decreased HbA1c and fasting glucose, but slightly increased body weight. No safety issues were raised for liraglutide; observed adverse events were mild and transient.
CONCLUSIONS—A once-daily dose of liraglutide provides efficacious glycemic control and is not associated with weight gain. Adverse events with the drug are mild and transient, and the risk of hypoglycemia is negligible.
- GLP-1, glucagon-like peptide 1
- HOMA, homeostasis model assessment
- ITT, intention to treat
- OHA, oral hypoglycemic agent
Footnotes
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D.R.M. has received consulting fees from Novo Nordisk, and the Oxford Centre for Diabetes, Endocrinology & Metabolism is supported by Novo Nordisk in an academic partnership.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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- Accepted March 7, 2004.
- Received October 21, 2003.
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