A double‐blind randomized study comparing the effects of continuing or not continuing rosiglitazone + metformin therapy when starting insulin therapy in people with Type 2 diabetes 1

Aims  To compare the efficacy and safety of either continuing or discontinuing rosiglitazone + metformin fixed‐dose combination when starting insulin therapy in people with Type 2 diabetes inadequately controlled on oral therapy. Methods  In this 24‐week double‐blind study, 324 individuals with Type 2 diabetes inadequately controlled on maximum dose rosiglitazone + metformin therapy were randomly assigned to twice‐daily premix insulin therapy (target pre‐breakfast and pre‐evening meal glucose ≤ 6.5 mmol/l) in addition to either rosiglitazone + metformin (8/2000 mg) or placebo. Results  Insulin dose at week 24 was significantly lower with rosiglitazone + metformin (33.5 ± 1.5 U/day, mean ±  se ) compared with placebo [59.0 ± 3.0 U/day; model‐adjusted difference −26.6 (95% CI −37.7, −15,5) U/day, P  < 0.001]. Despite this, there was greater improvement in glycaemic control [HbA 1c rosiglitazone + metformin vs. placebo 6.8 ± 0.1 vs. 7.5 ± 0.1%; difference −0.7 (−0.8, −0.5)%, P  < 0.001] and more individuals achieved glycaemic targets (HbA 1c  < 7.0% 70 vs. 34%, P  < 0.001). The proportion of individuals reporting at least one hypoglycaemic event during the last 12 weeks of treatment was similar in the two groups (rosiglitazone + metformin vs. placebo 25 vs. 27%). People receiving rosiglitazone + metformin in addition to insulin reported greater treatment satisfaction than those receiving insulin alone. Both treatment regimens were well tolerated but more participants had oedema [12 (7%) vs. 4 (3%)] and there was more weight gain [3.7 vs. 2.6 kg; difference 1.1 (0.2, 2.1) kg, P  = 0.02] with rosiglitazone + metformin. Conclusions  Addition of insulin to rosiglitazone + metformin enabled more people to reach glycaemic targets with less insulin, and was generally well tolerated.