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


METHODS
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).


RESULTS
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 A(1c) (HbA(1c)) (-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 HbA(1c) <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 HbA(1c) 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, beta-cell function and cardiovascular disease biomarkers were also observed. All treatments were similarly well tolerated.


CONCLUSIONS
Early addition of RSG to GLIM is an effective and well-tolerated treatment option to improve glycaemic control in sulphonylurea-treated patients with T2DM.
Rosenstock
J
J
Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA. juliorosenstock@dallasdiabetes.com
Chou
H S
HS
Matthaei
S
S
Seidel
D K
DK
Hamann
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D000077154:Rosiglitazone; D016037:Single-Blind Method; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D000077154:Rosiglitazone; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D014280:Triglycerides; C057619:glimepiride