Liraglutide, a Long-Acting Human Glucagon-Like Peptide-1 Analog, Given as Monotherapy Significantly Improves Glycemic Control and Lowers Body Weight Without Risk of Hypoglycemia in Patients With Type 2 Diabetes
- Tina Vilsbøll, MD, DMSC1,
- Milan Zdravkovic, MD, PHD2,
- Tu Le-Thi, MSC2,
- Thure Krarup, MD, DMSC1,
- Ole Schmitz, MD, DMSC3,
- Jean-Pierre Courrèges, MD4,
- Robert Verhoeven, MD5,
- Ingrid Bugánová, MD6 and
- Sten Madsbad, MD, DMSC7
- 1Department of Internal Medicine, Gentofte Hospital, Hellerup, Denmark
- 2Novo Nordisk, Bagsværd, Denmark
- 3Århus Hospital, Århus, Denmark
- 4Centre Hospitalier de Narbonne, Narbonne, France
- 5Gelre Ziekenhuis, Apeldoorn, the Netherlands
- 6Dibetologická Ambulancia, Zilina, Slovakia
- 7Hvidovre Hospital, Copenhagen, Denmark
- Address correspondence and reprint requests to Tina Vilsbøll, MD, DMSC, Internal Medicine F, Gentofte Hospital, Niels Andersens Vej 65, DK-2900 Hellerup, Denmark. E-mail:
Liraglutide is a long-acting human glucagon-like peptide-1 (GLP-1) analog (1–4), and the current study was undertaken to evaluate efficacy and safety after 14 weeks' treatment with liraglutide in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS—
Main inclusion criteria were patients aged ≥18 years with type 2 diabetes and A1C ≥7.5 and ≤10.0% (diet) or ≥7.0 and ≤9.5% (mono–oral antidiabetes drug); previous therapy was discontinued. Fasting plasma glucose (FPG) at randomization was 7–13 mmol/l. If FPG was >15 mmol/l during the study, the patient was withdrawn. The study was conducted in accordance with the Declaration of Helsinki (5). The study was double-blind, randomized (1:1:1:1), and placebo-controlled using three doses of liraglutide (0.65, 1.25, or 1.90 mg). The following main efficacy parameters were assessed: A1C, insulin, proinsulin, glucagon, fructosamine, lipids, home-measured seven-point plasma glucose profiles, and body weight. Safety parameters (adverse events, hypoglycemic episodes, clinical laboratory parameters, antibodies against liraglutide, vital signs, electrocardiogram, and thyroid (including ultrasonography) and parathyroid parameters were assessed. Liraglutide or placebo was administered in the evening (as in the most recently completed phase 2 study) (6) as once-daily subcutaneous injections in the abdomen or thigh.
Baseline characteristics are given in Table 1. The placebo group accounted for almost one-half of the patient withdrawals, primarily due to ineffective therapy. Withdrawals due to adverse events were infrequent and occurred at a comparable level in all groups (Table 1).
After 14 weeks of treatment, estimated change in A1C for placebo, 1.90, 1.25, or 0.65 mg was +0.29, −1.45, −1.40, and −0.98%, respectively (change for 1.90 mg vs. placebo: −1.74% [95% CI −2.18 to −1.29], P < 0.0001; 1.25 mg vs. placebo: −1.69% [−2.13 to −1.24], P < 0.0001; and 0.65 mg vs. placebo: −1.27% [−1.72 to −0.82], P < 0.0001). The …