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Initial treatment with fixed‐dose combination rosiglitazone/glimepiride in patients with previously untreated type 2 diabetes
Author(s) -
Chou H. S.,
Palmer J. P.,
Jones A. R.,
Waterhouse B.,
FerreiraCornwell C.,
Krebs J.,
Goldstein B. J.
Publication year - 2008
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2007.00753.x
Subject(s) - medicine , rosiglitazone , glimepiride , regimen , fixed dose combination , adiponectin , type 2 diabetes , adverse effect , gastroenterology , clinical endpoint , diabetes mellitus , pharmacology , endocrinology , insulin resistance , insulin , randomized controlled trial
Aim: This study assessed the efficacy and safety of two different dosing regimens of fixed‐dose combination (FDC) rosiglitazone (RSG) plus glimepiride (GLIM) compared with RSG or GLIM monotherapy in drug‐naive subjects with type 2 diabetes mellitus (T2DM). Methods: Drug‐naive subjects (n = 901) were enrolled into this 28‐week, double‐blind, parallel‐group study if their glycosylated haemoglobin A 1c (HbA 1c ) was >7.5% but ≤12%. Subjects were randomized to receive either GLIM [4 mg once daily (OD) maximal], RSG (8 mg OD maximal) or RSG/GLIM FDC regimen A (4 mg/4 mg OD maximal) or RSG/GLIM FDC regimen B (8 mg/4 mg OD maximal). Patients were assessed for efficacy and safety every 4 weeks for the first 12 weeks of the study, and at weeks 20 and 28. The primary efficacy endpoint was change in HbA 1c from baseline. Key secondary endpoints included the proportion of patients achieving recommended HbA 1c and fasting plasma glucose (FPG) targets; change from baseline in FPG, insulin, C‐reactive protein (CRP), adiponectin, free fatty acids and lipids; and percentage change in homeostasis model assessment‐estimated insulin sensitivity and β‐cell function. Safety evaluations included adverse‐event (AE) monitoring and clinical laboratory evaluations. Results: At week 28, both RSG/GLIM FDC regimens significantly reduced HbA 1c (mean ± s.d.: −2.4 ± 1.4% FDC regimen A; −2.5 ± 1.4% FDC regimen B) to a greater extent than RSG (−1.8 ± 1.5%) or GLIM (−1.7 ± 1.4%) monotherapy (model‐adjusted mean treatment difference, p < 0.0001 vs. both RSG and GLIM). Significantly more subjects achieved HbA 1c target levels of ≤6.5 and <7% with either RSG/GLIM FDC regimen compared with RSG or GLIM alone (model‐adjusted odds ratio, p < 0.0001 for both comparisons). Similarly, a significantly greater reduction in FPG levels was observed in subjects treated with the RSG/GLIM FDC [mean ± s.d. (mg/dl): −69.5 ± 57.5 FDC regimen A; −79.9 ± 56.8 FDC regimen B) compared with RSG (−56.6 ± 58.1) or GLIM (−42.2 ± 66.1) monotherapy (model‐adjusted mean treatment difference, p < 0.0001 for both comparisons). Improvement in CRP was also observed in subjects who were treated with a RSG/GLIM FDC or RSG monotherapy compared with GLIM monotherapy. RSG/GLIM FDC was generally well tolerated, with no new safety or tolerability issues identified from its monotherapy components, and a similar AE profile was observed across FDC regimens. The most commonly reported AE was hypoglycaemia, and the incidence of confirmed symptomatic hypoglycaemia (3.6–5.5%) was comparable among subjects treated with an RSG/GLIM FDC and GLIM monotherapy. Conclusions: Compared with RSG or GLIM monotherapy, the RSG/GLIM FDC improved glycaemic control with no significant increased risk of hypoglycaemia. RSG/GLIM FDC provides an effective and well‐tolerated treatment option for drug‐naive individuals with T2DM.