Potential benefits of early addition of rosiglitazone in combination with glimepiride in the treatment of type 2 diabetes

• Published in: Diabetes, obesity & metabolism Vol. 10; no. 10; pp. 862 - 873
• Main Authors: Rosenstock, J, Chou, H.S, Matthaei, S, Seidel, D.K, Hamann, A
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.10.2008; Blackwell Publishing Ltd
• Subjects: Adult; Aged; Aged, 80 and over; Blood Glucose - analysis; Cholesterol, LDL - blood; combination treatment; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; glimepiride; glycaemic control; Glycated Hemoglobin A - analysis; Humans; hypoglycaemia; Hypoglycemic Agents - therapeutic use; Insulin - blood; Insulin Resistance; Male; Metformin - therapeutic use; Middle Aged; rosiglitazone; Single-Blind Method; Sulfonylurea Compounds - therapeutic use; Thiazolidinediones - therapeutic use; Treatment Outcome; Triglycerides - blood; type 2 diabetes mellitus
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2007.00815.x

To assess the efficacy and tolerability of early combination therapy with rosiglitazone (RSG) and glimepiride (GLIM) vs. GLIM monotherapy in patients with type 2 diabetes mellitus (T2DM). Strategies for the addition of RSG in combination with GLIM were evaluated with data from two randomized, double-blind, placebo (PBO)-controlled studies. Study A - addition of RSG (4 or 8 mg) or PBO to continued GLIM 3 mg once daily; study B - addition of low-dose RSG (4 mg) prior to uptitration of GLIM (from 2 to 4 mg) vs. continued uptitration of GLIM (from 2 to 8 mg). Study A reported significant reductions in fasting plasma glucose (FPG) from baseline to week 26 with the addition of both 4 and 8 mg RSG to GLIM 3 mg [-21 mg/dl (-1.2 mmol/l), p = 0.0019 and -43 mg/dl (-2.4 mmol/l), p < 0.0001, respectively] and in haemoglobin A₁c (HbA₁c) (-0.63%, p = 0.00015 and -1.17%, p < 0.0001, respectively) from a baseline of 8.2 and 8.1%, respectively. At the end of the study, target HbA₁c <7.0% was achieved in 43 and 68% of patients in the RSG 4 mg + GLIM and RSG 8 mg + GLIM groups, respectively, compared with 32% in the PBO + GLIM (GLIM alone) group. In study B, addition of RSG to GLIM reduced mean FPG and HbA₁c levels at week 24 from baseline [-28 mg/dl (-1.5 mmol/l), p < 0.0001, and -0.68%, p < 0.0001, respectively]. There were no significant changes with GLIM monotherapy in either study. Favourable effects of RSG + GLIM on insulin sensitivity, β-cell function and cardiovascular disease biomarkers were also observed. All treatments were similarly well tolerated. Early addition of RSG to GLIM is an effective and well-tolerated treatment option to improve glycaemic control in sulphonylurea-treated patients with T2DM.