Aims  To compare glucose control over 18 months between rosiglitazone oral combination therapy and combination metformin and sulphonylurea in people with Type 2 diabetes.

Methods  RECORD, a multicentre, parallel‐group study of cardiovascular outcomes, enrolled people with an HbA_1c of 7.1–9.0% on maximum doses of metformin or sulphonylurea. If on metformin they were randomized to add‐on rosiglitazone or sulphonylurea (open label) and if on sulphonylurea to rosiglitazone or metformin. HbA_1c was managed to ≤ 7.0% by dose titration. A prospectively defined analysis of glycaemic control on the first 1122 participants is reported here, with a primary outcome assessed against a non‐inferiority margin for HbA_1c of 0.4%.

Results  At 18 months, HbA_1c reduction on background metformin was similar with rosiglitazone and sulphonylurea [difference 0.07 (95% CI −0.09, 0.23)%], as was the change when rosiglitazone or metformin was added to sulphonylurea [0.06 (−0.09, 0.20)%]. At 6 months, the effect on HbA_1c was greater with add‐on sulphonylurea, but was similar whether sulphonylurea was added to rosiglitazone or metformin. Differences in fasting plasma glucose were not statistically significant at 18 months [rosiglitazone vs. sulphonylurea −0.36 (−0.74, 0.02) mmol/l, rosiglitazone vs. metformin −0.34 (−0.73, 0.05) mmol/l]. Increased homeostasis model assessment insulin sensitivity and reduced C‐reactive protein were greater with rosiglitazone than metformin or sulphonylurea (all P ≤ 0.001). Body weight was significantly increased with rosiglitazone compared with sulphonylurea [difference 1.2 (0.4, 2.0) kg, P = 0.003] and metformin [difference 4.3 (3.6, 5.1) kg, P < 0.001].

Conclusions  In people with diabetes, rosiglitazone in combination with metformin or sulphonylurea was demonstrated to be non‐inferior to the standard combination of metformin + sulphonylurea in lowering HbA_1c over 18 months, and produces greater improvements in C‐reactive protein and basal insulin sensitivity but is also associated with greater weight gain.