Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial.

AIMS/OBJECTIVE: Conflicting data regarding cardiovascular effects of thiazolidinediones (TZDs) and extra-skeletal effects of vitamin D supported the need for a definitive trial. The Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) trial aimed to assess the effects of TZDs (rosiglitazone and pioglitazone) on cardiovascular outcomes and the effects of vitamin D (cholecalciferol) on cancers and mortality. METHODS: A large multicentre 3 × 2 factorial double-blind placebo-controlled randomised trial recruited from outpatient primary care and specialty clinics in 33 countries. From June 2009 to July 2010, 1,332 people with type 2 diabetes and other cardiovascular risk factors aged ≥ 50 years whose HbA(1c) was 6.5-9.5% (48-80 mmol/mol) when using two or fewer glucose-lowering drugs were randomised by a central computer system to placebo (n = 541), rosiglitazone 4-8 mg/day (n = 399) or pioglitazone 30-45 mg/day (n = 392); 1,221 participants were randomised to placebo (n = 614) or vitamin D 1,000 IU/day (n = 607). Participants and all study personnel were blind to treatment allocation. The primary outcome for the TZD arm was the composite of myocardial infarction, stroke or cardiovascular death, and for the vitamin D arm it was cancer or all-cause death. All randomised participants were included in the primary analysis. RESULTS: From the study design, 16,000 people were to be followed for approximately 5.5 years. However, the trial was stopped prematurely because of regulatory concerns after a mean of 162 days without consideration of the accrued data. In the TZD arm, the cardiovascular outcome occurred in five participants (0.9%) in the placebo groups and three participants (0.4%) in the TZD groups (two allocated to pioglitazone, one to rosiglitazone). In the vitamin D arm, the primary outcome occurred in three participants (0.5%) in the placebo group and in two participants (0.3%) receiving vitamin D. Adverse events were comparable in all groups. CONCLUSIONS/INTERPRETATION: Uncertainty persists regarding the clinically relevant risks and benefits of TZDs and vitamin D because of the early cancellation of this comprehensive trial.

Feasibility of insulin-glucose infusion in diabetic patients with acute myocardial infarction. A report from the multicenter trial: DIGAMI.

OBJECTIVE: To investigate the effect of insulin-glucose infusion on metabolic control and hypoglycemic episodes and its feasibility and safety in patients with diabetes and myocardial infarction (MI) compared with conventional treatment. RESEARCH DESIGN AND METHODS: Of 327 patients with suspected acute MI 158 were randomized to insulin-glucose infusion for at least 24 h and 169 received conventional therapy. We determined the 24-h blood glucose profile in the infusion group, the degree of metabolic control, hypoglycemic events, and in-hospital complications within the two study groups. RESULTS: Blood glucose fell from 14.6 +/- 2.9 to 9.2 +/- 2.9 mM during the first 24 h in patients receiving insulin-glucose and from 15.8 +/- 4.3 to 12.0 +/- 4.4 mM in control patients (P < 0.01). Serum potassium decreased 0.21 +/- 0.56 mM in the infusion group (P < 0.001) and 0.11 +/- 0.59 mM in the control group (P < 0.05). The difference between the groups was not significant. Twenty-eight of the 158 patients developed an episode of hypoglycemia (blood glucose < 3.0 mM) during the insulin-glucose infusion. There were no significant differences in the number of episodes of ventricular tachyarrhythmias or in ischemic events between patients with and without hypoglycemia. CONCLUSIONS: The protocol outlined in this study gives more rapid and better metabolic control than does conventional treatment. This treatment seems to be a feasible alternative for clinical attempts. Before it can be recommended for general use, the impact on mortality needs to be evaluated.