The once-daily human glucagon-like peptide-1 analog, liraglutide, improves β-cell function in Japanese patients with type 2 diabetes

Yutaka Seino, Mads Frederik Rasmussen, Per Clauson, Kohei Kaku, Yutaka Seino, Mads Frederik Rasmussen, Per Clauson, Kohei Kaku

Abstract

Aims/Introduction: β-cell function was evaluated by homeostasis model assessment of β-cell function (HOMA-B) index, proinsulin:insulin and proinsulin:C-peptide ratios in adult, Japanese type 2 diabetes patients receiving liraglutide.

Materials and methods: Data from two randomized, controlled clinical trials (A and B) including 664 Japanese type 2 diabetes patients (mean values: glycated hemoglobin [HbA1c] 8.61-9.32%; body mass index [BMI] 24.4-25.3 kg/m(2)) were analyzed. In two 24-week trials, patients received liraglutide 0.9 mg (n = 268) or glibenclamide 2.5 mg (n = 132; trial A), or liraglutide 0.6, 0.9 mg (n = 176) or placebo (n = 88) added to previous sulfonylurea therapy (trial B).

Results: Liraglutide was associated with improved glycemic control vs sulfonylurea monotherapy or placebo. In liraglutide-treated groups in trials A and B, area under the curve (AUC) insulin 0-3 h was improved (P < 0.001 for all) and the AUCinsulin 0-3 h:AUCglucose 0-3 h ratio was increased (estimated treatment difference [liraglutide-comparator] 0.058 [0.036, 0.079]). HOMA-B significantly increased with liraglutide relative to comparator in trial B (P < 0.05), but not in trial A. The reduction in fasting proinsulin:insulin ratio was 50% greater than in comparator groups.

Conclusions: In Japanese type 2 diabetes patients, liraglutide was associated with effective glycemic control, restoration of prandial insulin response and indications of improved β-cell function. This trial was registered with Clinicaltrials.gov (trial A: no. NCT00393718/JapicCTI-060328 and trial B: no. NCT00395746/JapicCTI-060324). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00193.x, 2012).

Keywords: Insulin‐secreting cells; Liraglutide; Type 2 diabetes.

Figures

Figure 1
Figure 1
Insulin and glucagon profiles and area under the curve (AUC)0–3 h values for insulin and glucagon by trial (A and B) and by treatment group in the 3 h after the standard meal test at the end of the study period. (a) Insulin profiles (0–3 h) and comparison of AUCinsulin 0–3 h by trial and by treatment group. (b) Glucagon profiles (0–3 h) and comparison of AUCglucagon 0–3 h by trial and by treatment group. Data are last observation carried forward at week 24. Errors bars are standard error. SU, sulfonylureas.

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