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

Abstract

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 < or = 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.

FIGURE 1

Time courses for daily insulin dose, HbA_1c and clinic FPG for people with Type 2 diabetes starting insulin while continuing rosiglitazone + metformin (□) or transferring to placebo (•). Data are mean ± se for ITT populations with LOCF, except for dose which is without LOCF. For statistical significance see Results and Table 2.