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

AIM:

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.

METHOD:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: A Hamann, J Garcia-Puig, G Paul, J Donaldson, M Stewart
• Journal: Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association (Exp Clin Endocrinol Diabetes) Vol. 116 Issue 1 Pg. 6-13 (Jan 2008) ISSN: 0947-7349 [Print] Germany
• PMID: 18095238 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Glycated Hemoglobin A
• Hypoglycemic Agents
• Lipids
• Sulfonylurea Compounds
• Thiazolidinediones
• Rosiglitazone
• Metformin

Topics

• Blood Pressure
• Diabetes Mellitus, Type 2 (complications, drug therapy, physiopathology)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Glycated Hemoglobin (analysis)
• Humans
• Hypoglycemia (epidemiology)
• Hypoglycemic Agents (administration & dosage)
• Insulin Resistance
• Insulin-Secreting Cells (physiology)
• Lipids (blood)
• Male
• Metformin (administration & dosage, adverse effects)
• Obesity (complications, physiopathology)
• Rosiglitazone
• Sulfonylurea Compounds (administration & dosage, adverse effects)
• Thiazolidinediones (administration & dosage, adverse effects)