Weng J, Li Y, Xu W, et al. 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. Lancet 2008;371:1753–60
This study compared two intensive insulin regimens with oral hypoglycaemic agents in newly diagnosed patients with T2DM (fasting plasma glucose 7.0 to 16.7mmol/L, mean BMI 25kg/m2). After control of blood glucose had been achieved for two weeks the interventions were withdrawn and all patients were monitored on diet and exercise. It found that short-term, intensive insulin therapy increased the number of patients who maintained normoglycaemia at one year on diet and exercise alone compared with short-term oral hypoglycaemic agents .
What is the background to this?
Previous small studies have suggested that, in patients with newly diagnosed type 2 diabetes, short-term intensive insulin therapies could improve β-cell function and result in extended remissions in which only diet was needed to maintain normoglycaemia.
What does this study claim?
More patients achieved target glycaemic control in the insulin groups (97·1% with continuous subcutaneous insulin infusion [CSII] and 95·2% in multiple daily insulin injections [MDI]) in less time (4·0 days in CSII and 5·6 days in MDI) than those treated with oral hypoglycaemic agents (83·5% and 9·3 days), p < 0.0001. 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).
As reported in an accompanying article, the study has limitations. A difference of a few days in the time taken to achieve normoglycaemia with insulin compared with oral hypoglycaemic agents is neither surprising nor likely to translate into significant short or long term outcomes that mean patients live longer or better. Significantly more patients requiring only diet and exercise after a year is more interesting but that benefit may not necessarily be maintained over a longer period nor result in fewer major diabetes-related events – in particular heart attacks, strokes, blindness and end stage renal failure. In addition the study reports limited description of β-cell function and glycaemic control during the year, there is an absence of clinical characterisation of the remission and non-remission groups at one year, and the issue of the single ethnic study group with a mean BMI very different from other populations with newly diagnosed T2DM. The use of intensive insulin therapy to achieve remission in patients with newly diagnosed type 2 diabetes requires further investigation, and more studies are required in larger numbers of patients, from different populations, over a longer period of time, with patient-orientated outcomes and including a health economic evaluation. Although the results from this study are interesting, we should not change our practice on the basis of this single trial.
Design: Randomised controlled trial in nine centres in China.
Patients: 382 patients aged 25–70 years with newly diagnosed type 2 diabetes – fasting plasma glucose 7.0 to 16.7mmol/L. Mean age 51 years, mean body mass index 25 kg/m2 and mean fasting plasma glucose 11.2 mmol/L.
Interventions and comparison: Short-term intensive therapy with multiple daily insulin (MDI) vs. continuous subcutaneous insulin infusion (CSSI) vs. oral hypoglycaemic agents (gliclazide, metformin, or both). Doses were titrated and treatments were maintained for two weeks after normoglycaemia was achieved After the interventions were stopped, patients were followed up on diet and physical exercise alone.
Outcomes: The primary endpoints were the time of glycaemic remission and remission rate at one year.
Results: More patients achieved target glycaemic control in the insulin groups (97·1% in CSII and 95·2% in MDI) in less time (4·0 days in CSII and 5·6 days in MDI) than those treated with oral hypoglycaemic agents (83·5% and 9·3 days). 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).
Sponsorship: 973 programme from the Chinese Government, the natural Science Foundation of Guangdong Province Government, Novo Nordisk (China) and Roche Diagnostics (Shanghai).