Rosiglitazone RECORD study: glucose control outcomes at 18 months

Abstract

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 < or = 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 < or = 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.

FIGURE 1

Flow diagram of the study design. This diagram includes 11 participants whose completer status was unknown at the time the database was locked for analysis, but whose status was subsequently established. *For definition of intention-to-treat (ITT) population, see text. †Includes people who moved to the Post-Randomized Treatment phase of the study, and people who withdrew completely. ‡‘Other’ reasons include lost to follow-up, consent withdrawn, sponsor terminated, non-compliance and miscellaneous reasons, including one on metformin + rosiglitazone group with ALT > 3 × upper limit of normal. §Two participants on sulfonylurea + metformin withdrew because of an adverse event in error, later resumed assigned therapy, and are not included as ‘withdrawn’. OGLD, oral glucose-lowering drug.

FIGURE 2

Time course for HbA_1c (upper panels) and fasting plasma glucose (FPG; lower panels) during the 18-month treatment period. Data are model adjusted mean ± se. Left-hand panels show addition of rosiglitazone (▵; n = 253) or sulfonylurea (▴; n = 263) to metformin; right-hand panels show addition of rosiglitazone (□; n = 301) or metformin (▪; n = 272) to sulfonylurea.