Comparison of uptitration of gliclazide with the addition of rosiglitazone to gliclazide in patients with type 2 diabetes inadequately controlled on half-maximal doses of a sulphonylurea

Abstract.

Patients with type 2 diabetes who are inadequately controlled on a half-maximal dose of a sulphonylurea may be managed by either increasing the dose of sulphonylurea or adding another agent. In this study, 471 patients inadequately controlled (fasting plasma glucose [FPG] ≥7.0 and ≤15.0 mmol/l) on 160 mg/day gliclazide were randomised to receive either the addition of rosiglitazone (4 mg b.i.d.) or to have their gliclazide uptitrated to a maximum of 320 mg/day during a 26-week treatment period. A reduction in HbA_1c of 1.3% (p=0.0001) was observed in the combination treatment group compared to the uptitrated gliclazide group after 26 weeks. The proportion of patients who achieved an HbA_1c value <7% was also greater in this group (48% vs. 22%). FPG was reduced by 3.0 mmol/l (p=0.0001) in the rosiglitazone plus gliclazide group compared to the uptitrated gliclazide group after 26 weeks. The improved efficacy of the combination treatment was accompanied by increased incidence of signs or symptoms suggestive of hypoglycaemia compared with uptitrating the gliclazide dose (6% vs. 2%). Only 1% of patients reported severe hypoglycaemia. The combination treatment led to increases in plasma lipoproteins, and more patients experienced oedema (11% vs. 3%). A significant increase in body weight was observed in patients receiving rosiglitazone plus gliclazide versus uptitrated gliclazide (3.4 kg; p=0.0001). The addition of rosiglitazone (4 mg b.i.d.) to gliclazide (160 mg/day) was well tolerated, and significantly more effective in improving glycaemia than uptitrating gliclazide to 320 mg/day.