Effect of intensive insulin therapy on β-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes:: a multicentre randomised parallel-group trial

Background Early intensive insulin therapy in patients with newly diagnosed type 2 diabetes might improve beta-cell function and result in extended glycaemic remissions. We did a multicentre, randomised trial to compare the effects of transient intensive insulin therapy (continuous subcutaneous insulin infusion [CSII] or multiple daily insulin injections [MDI]) with oral hypoglycaemic agents on beta-cell function and diabetes remission rate. Methods 382 patients, aged 25-70 years, were enrolled from nine centres in China between September, 2004, and October, 2006. The patients, with fasting plasma glucose of 7.0-16.7 mmol/L, were randomly assigned to therapy with insulin (CSII or MDI) or oral hypoglycaemic agents for initial rapid correction of hyperglycaemia. Treatment was stopped after normoglycaemia was maintained for 2 weeks. Patients were then followed-up on diet and exercise alone. Intravenous glucose tolerance tests were done and blood glucose, insulin, and proinsulin were measured before and after therapy withdrawal and at 1-year follow-up. Primary endpoint was time of glycaemic remission and remission rate at 1 year after short-term intensive therapy. Analysis was per protocol. This study was registered with ClinicalTrials.gov, number NCT00147836. Findings More patients achieved target glycaemic control in the insulin groups (97.1% [133 of 137] in CSII and 95.2% [118 of 124] in MDI) in less time (4. 0 days [SD 2.51 in CSII and 5.6 days [SD 3.8] in MDI) than those treated with oral hypoglycaemic agents (83.5% [101 of 1211 and 9.3 days [SD 5.31). Remission rates after 1 year were significantly higher in the insulin groups (51. 1% in CSII and 44.9% in MDI) than in the oral hypoglycaemic agents group (26.7%; p=0.0012). beta-cell function represented by HOMA B and acute insulin response improved significantly after intensive interventions. The increase in acute insulin response was sustained in the insulin groups but significantly declined in the oral hypoglycaemic agents group at 1 year in all patients in the remission group. Interpretation Early intensive insulin therapy in patients with newly diagnosed type 2 diabetes has favourable outcomes on recovery and maintenance of beta-cell function and protracted glycaemic remission compared with treatment with oral hypoglycaernic agents. Funding 973 Programme from the Chinese Government, the Natural Science Foundation of Guangdong Province Government, Novo Nordisk (China), and Roche Diagnostics (Shanghai).