PMID- 16330291
OWN - NLM
STAT- MEDLINE
DCOM- 20060201
LR  - 20221207
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 27
IP  - 10
DP  - 2005 Oct
TI  - Rosiglitazone/metformin fixed-dose combination compared with uptitrated metformin 
      alone in type 2 diabetes mellitus: a 24-week, multicenter, randomized, 
      double-blind, parallel-group study.
PG  - 1548-61
AB  - BACKGROUND: Management of type 2 diabetes mellitus (DM) that involves uptitration 
      of monotherapy to the maximum dose has been associated with delays in achieving 
      glycemic control and an increased number of adverse events (AEs). Studies have 
      reported the benefits of adding a thiazolidinedione to metformin (MET), but none 
      has compared the effect of adding a thiazolidinedione to MET versus increasing 
      the daily dose of MET to 3 g. OBJECTIVE: The goal of this study was to 
      investigate the benefits of fixed-dose combination rosiglitazone and MET 
      (RSG/MET) compared with high-dose MET monotherapy in patients with type 2 DM. 
      METHODS: This was a 24-week, multicenter, randomized, double-blind, 
      parallel-group study. Patients previously treated with MET entered a 4-week, 
      single-blind, run-in period with MET 2 g/d and were then randomized to RSG/MET 4 
      mg/2 g per day or MET 2.5 g/d. At week 8, medication was escalated to RSG/MET 8 
      mg/2 g per day or MET 3 g/d. The primary efficacy end point was change in 
      glycosylated hemoglobin (HbA1c) at week 24. Tolerability was assessed, including 
      the frequency and severity of AEs. RESULTS: A total of 568 patients comprised the 
      safety population (MET, 280; RSG/MET, 288) and 551 formed the intent-to-treat 
      group (MET, 272; RSG/MET, 279). Baseline characteristics of the safety population 
      were comparable in the 2 groups; body mass index (mean [SD]) was 32.2 (4.8) 
      kg/m(2) and 32.1 (4.9) kg/m(2) in the RSG/MET and MET groups, respectively. 
      RSG/MET reduced HbA(1c) (mean [SD]) from 7.4% (1.0%) to 7.1% (1.1%) at week 24, 
      compared with a reduction from 7.5% (1.0%) to 7.4% (1.1%) with MET (treatment 
      difference, -0.22%; P = 0.001). Fasting plasma glucose (mean [SD]) was reduced 
      from 166.2 (29) to 144.1 (33) mg/dL with RSG/MET and from 169.3 (33) to 164.0 
      (37) mg/dL with MET (treatment difference, -18.3 mg/dL; P < 0.001). In addition, 
      54% of patients treated with RSG/MET achieved HbA(1c) levels <7.0%, compared with 
      36% with MET (odds ratio, 2.42; P < 0.001). RSG/MET increased homeostasis model 
      assessment (HOMA) estimates of insulin sensitivity by 34.4% versus 6.5% with MET 
      (treatment difference, 24.8%; P < 0.001). HOMA beta-cell function increased by 
      15.9% with RSG/MET versus 2.5% with MET (treatment difference, 14.0%; P < 0.001). 
      RSG/MET decreased C-reactive protein by a mean of 39.4% versus 16.0% with MET 
      (treatment difference, -33.8%; P < 0.001). RSG/MET was generally well tolerated, 
      with the majority of AEs mild to moderate in nature. Serious AEs were reported in 
      3% of patients receiving RSG/MET and 2% with MET. Overall rates of 
      gastrointestinal AEs were 23% with RSG/MET and 26% with MET; however, there was 
      an increased incidence of diarrhea (14% vs 6%) and abdominal pain (9% vs 6%) with 
      MET. There was a mean (SE) increase in weight with RSG/MET (1.3 [0.22] kg) and a 
      mean decrease (-0.9 [0.26] kg) with MET. Patients receiving RSG/MET reported 
      improvements in treatment satisfaction compared with MET. CONCLUSIONS: In this 
      study, the RSG/MET fixed-dose combination (8 mg/2 g per day) was an effective and 
      well-tolerated treatment for type 2 DM and enabled more patients to reach 
      glycemic targets than high-dose MET (3 g/d).
FAU - Bailey, Clifford J
AU  - Bailey CJ
AD  - Aston University, Aston Triangle, Birmingham, UK. C.J.Bailey@aston.ac.uk
FAU - Bagdonas, Alfredas
AU  - Bagdonas A
FAU - Rubes, Josip
AU  - Rubes J
FAU - McMorn, Stephen O
AU  - McMorn SO
FAU - Donaldson, Jill
AU  - Donaldson J
FAU - Biswas, Nandita
AU  - Biswas N
FAU - Stewart, Murray W
AU  - Stewart MW
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Blood Glucose)
RN  - 0 (Drug Combinations)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Lipids)
RN  - 0 (Thiazolidinediones)
RN  - 05V02F2KDG (Rosiglitazone)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Algorithms
MH  - Blood Glucose/analysis
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy
MH  - Double-Blind Method
MH  - Drug Combinations
MH  - Europe
MH  - Female
MH  - Glycated Hemoglobin/analysis
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/*therapeutic use
MH  - Insulin/blood
MH  - Lipids/blood
MH  - Male
MH  - Metformin/administration & dosage/*therapeutic use
MH  - Middle Aged
MH  - Rosiglitazone
MH  - Thiazolidinediones/administration & dosage/*therapeutic use
MH  - Time Factors
EDAT- 2005/12/07 09:00
MHDA- 2006/02/02 09:00
CRDT- 2005/12/07 09:00
PHST- 2005/08/26 00:00 [accepted]
PHST- 2005/12/07 09:00 [pubmed]
PHST- 2006/02/02 09:00 [medline]
PHST- 2005/12/07 09:00 [entrez]
AID - S0149-2918(05)00200-6 [pii]
AID - 10.1016/j.clinthera.2005.10.012 [doi]
PST - ppublish
SO  - Clin Ther. 2005 Oct;27(10):1548-61. doi: 10.1016/j.clinthera.2005.10.012.