OBJECTIVE: To assess the metabolic and cardiovascular effects of metformin in patients with type 2 diabetes (DM2) who use insulin. DESIGN: Prospective randomised placebo-controlled clinical study. METHODS: The effects of metformin in 390 DM2 patients during a follow-up period of 4.3 years were studied. Either metformin or placebo was added to the insulin therapy at the maximum tolerated dose (850 mg 1-3 times daily). The primary endpoint was an aggregate score of microvascular and macrovascular events plus acute mortality. The secondary endpoints were separate aggregate scores of macrovascular events plus acute mortality on the one hand and microvascular events on the other. In addition, effects on the HbA1c value, insulin requirement, lipid values, blood pressure, body weight, and BMI were analysed. The trial is registered with Clinical Trials Identifier NCT00375388. RESULTS: Metformin treatment prevented weight gain (-3.07 kg compared to placebo; 95% CI: -3.85 to -2.28; p < 0.001), improved glycaemic control (HbA1c: -0.4%; 95% CI: -0.55 to -0.25; p < 0.001), and reduced insulin requirements (-19.63 IU/day; 95% CI: -24.91 to -14.36; p < 0.001). Metformin was not associated with an improvement in the primary endpoint. It was, however, associated with an improvement in the secondary, macrovascular endpoint (hazard ratio 0.61 (95% CI: 0.40 to 0.94); p = 0.02), which was partly explained by the effect on body weight. The number of patients that had to be treated to prevent one macrovascular event was 16.1 (95% CI: 9.2 to 66.6). CONCLUSION: Metformin, added to insulin in patients with DM2, led to a more favourable body weight, an improved glucose regulation with less insulin and a lower risk of macrovascular events. These findings support the policy of continuing the treatment with metformin in patients with DM2 who start to use insulin.
|Journal||Nederlands Tijdschrift voor Geneeskunde|
|Publication status||Published - 1 Jan 2009|