Comparison of fixed-dose rosiglitazone/metformin combination therapy with sulphonylurea plus metformin in overweight individuals with Type 2 diabetes inadequately controlled on metformin alone.
ABSTRACT This 52-week, randomized, double-blind, parallel-group study was designed to compare rosiglitazone/metformin fixed-dose combination therapy with combination sulphonylurea plus metformin therapy in overweight individuals with inadequately controlled type 2 diabetes mellitus.
Individuals with inadequate glycaemic control (HbA (1c)> or =7%) while on metformin monotherapy (> or =0.85 g/day) entered a 4-week run-in period during which they received metformin 2 g/day. At the end of the run-in, individuals with fasting plasma glucose > or =7.0 mmol/l were randomized to treatment with metformin (2 g/day) and either rosiglitazone (4 mg/day; RSG+MET [N=294]) or a sulphonylurea (glibenclamide 5 mg/day or gliclazide 80 mg/day; SU+MET [N=302]). Medications were up-titrated to maximum tolerated doses (rosiglitazone 8 mg, glibenclamide 15 mg or gliclazide 320 mg plus metformin 2 g/day) during the first 12 weeks of double-blind treatment. The primary efficacy end point was the change in HbA (1c) from baseline after 52 weeks of treatment.
RSG+MET was non-inferior to SU+MET with respect to changes in HbA (1c) after one year of treatment (DeltaHbA (1c)= -0.78% and -0.86%, respectively; treatment difference =0.09%, 95% CI=-0.08, 0.25). The HbA (1c) reductions with RSG+MET, but not SU+MET, were accompanied by significant improvements in measures of beta-cell function including proinsulin:insulin ratio. The degree of beta-cell failure was significantly greater with SU+MET compared to RSG+MET as measured by the coefficient of failure (0.543 vs. 0.055 HbA (1c)%/year, respectively, p=0.0002). The proportion of individuals who experienced hypoglycaemic events was significantly (p<0.0001) lower with RSG+MET (6%) than with SU+MET (30%). Diastolic ambulatory blood pressure and cardiovascular biomarkers (high-sensitivity C-reactive protein and plasminogen activator inhibitor-1) were also reduced following one year of treatment with RSG+MET but not SU+MET. Both treatments were generally well tolerated.
Fixed-dose combination therapy with rosiglitazone/metformin is non-inferior to sulphonylurea plus metformin combination therapy in reducing HbA (1c) over one year of treatment. Improvements in measures of beta-cell function suggest that the improvements in glycaemic control may be better maintained in long-term therapy with the rosiglitazone/metformin combination.
- SourceAvailable from: Nalinee Poolsup[Show abstract] [Hide abstract]
ABSTRACT: Background and Aim. Diabetes mellitus is a chronic disease that has a great impact on patients and society. Metformin monotherapy is capable of maintaining a target glycemic control only for a short term. The aim of this study was to determine the efficacy of combination therapy of metformin with any antidiabetic agents in type 2 diabetes mellitus (T2DM) patients. Methods. Reports of randomized controlled trials (RCTs) of combination therapy of metformin with various antidiabetic agents in T2DM failing metformin alone were identified. Results. Eight studies were identified in our paper. Thiazolidinediones (TZDs) were as effective as dipeptidyl peptidase IV inhibitors (DPP IV inhs) in reducing HbA1c value (pooled mean difference −0.03%; 95% CI −0.16 to 0.10%). In comparison between TZDs and sulphonylureas (SUs), TZDs reduced fasting plasma insulin (FPI) more effectively than SUs (pool mean difference −5.72 μU/mL; 95% CI −8.21 to −3.22 μU/mL, P < 0.00001), but no significant differences were detected in the effects on HbA1c and fasting plasma glucose (FPG) (pooled mean difference −2.19 mg/dL; 95% CI −11.32 to 6.94 mg/dL, P = 0.64). Conclusions. Our study showed that TZDs reduced FPG better than did DPP IV inhs and decreased FPI more than did SUs.03/2012; 2012:798146. DOI:10.5402/2012/798146