Effect of metformin plus roziglitazone compared with metformin alone on glycaemic control in well-controlled Type 2 diabetes.
OBJECTIVE
To investigate the effect of metformin plus roziglitazione (RSGMET) compared with metformin alone (MET) on glycaemic control in well-controlled Type 2 diabetes.


METHODS
Subjects (drug naïve or those on glucose-lowering monotherapy) were randomized (n = 526), following a 4-week placebo run-in period, to RSGMET [4 mg rosiglitazone (RSG)/500 mg MET] or MET 500 mg. From weeks 2-18, medication was escalated every 4 weeks (based on gastrointestinal tolerability), then remained at RSGMET 8 mg/2 g or MET 3 g for 14 weeks.


RESULTS
RSGMET reduced HbA(1c) from 7.2 +/- 0.6 to 6.7 +/- 0.8% at week 32, compared with a reduction from 7.2 +/- 0.6 to 6.8 +/- 0.9% with MET (treatment difference -0.13%; P = 0.0357). More subjects achieved an HbA(1c) value of </= 6.5% at week 32 with RSGMET (51.6 vs. 43.7%), but the treatment difference was not significant (odds ratio 1.37, P = 0.0949). RSGMET produced larger reductions from baseline in mean fasting plasma glucose (adjusted difference -0.62 mmol/l, P < 0.0001), with the odds ratio of achieving a target of < 7.0 mmol/l being 2.33 (P < 0.0001). Statistically significant differences in favour of RSGMET relative to MET were seen for homeostatic model assessment (HOMA)-derived estimates of insulin sensitivity and pancreatic B-cell function, C-reactive protein (CRP), and systolic blood pressure. Overall rates of gastrointestinal adverse events (relevant to the known profile of MET) were comparable, but with a lower incidence of diarrhoea (8 vs. 18%) with RSGMET. Hypoglycaemia was reported in </= 7% subjects per group.


CONCLUSIONS
RSGMET provided similar short-term glycaemic control to MET with greater improvements in estimates of insulin sensitivity, B-cell function and CRP, with less diarrhoea and low risk of biochemical hypoglycaemia, suggesting that early use of combination therapy may be appropriate.
Stewart
M W
MW
Solli Klinikk, Jessheim, Norway. Murray_W_Stewart@gsk.com
Cirkel
D T
DT
Furuseth
K
K
Donaldson
J
J
Biswas
N
N
Starkie
M G
MG
Phenekos
C
C
Hamann
A
A
D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin