Short-term intensive insulin therapy in type 2 diabetes mellitus: a systematic review and meta-analysis

Background Studies have shown that, when implemented early in the course of type 2 diabetes mellitus, treatment with intensive insulin therapy for 2-3 weeks can induce a glycaemic remission, wherein patients are able to maintain normoglycaemia without any anti-diabetic medication. We thus did a systematic review and meta-analysis of interventional studies to assess the effect of short-term intensive insulin therapy on the pathophysiological defects underlying type 2 diabetes mellitus (pancreatic beta-cell dysfunction and insulin resistance) and identify clinical predictors of remission. Methods We identified studies published between 1950 and Nov 19, 2012, which assessed the effect of intensive insulin therapy on beta-cell function or insulin resistance, or both, or assessed long-term drug-free glycaemic remission in adults aged 18 years or older with newly diagnosed type 2 diabetes mellitus. We calculated pooled estimates by random-effects model. This study is registered with International Prospective Register of Systematic Reviews, number CRD42012002829. Findings We identified 1645 studies of which seven fulfilled inclusion criteria (n=839 participants). Five studies were non-randomised. A pooled analysis of the seven studies showed a post-intensive insulin therapy increase in Homeostasis Model Assessment of beta-cell function as compared with baseline (1.13, 95% CI 1.02 to 1.25) and a decrease in Homeostasis Model Assessment of Insulin Resistance (-0.57, -0.84 to -0.29). In the four studies that assessed glycaemic remission (n=559 participants), the proportion of participants in drug-free remission was about 66.2% (292 of 441 patients) after 3 months of follow-up, about 58 9% (222 of 377 patients) after 6 months, about 46.3% (229 of 495 patients) after 12 months, and about 42.1% (53 of 126 patients) after 24 months. Patients who achieved remission had higher body-mass index than those who did not achieve remission (1.06 kg/m(2), 95% CI 0.55 to 1.58) and lower fasting plasma glucose (-0.59 mmol/L, 95% CI -1.11 to -0.07) at baseline. Interpretation Short-term intensive insulin therapy can improve the underlying pathophysiology in early type 2 diabetes mellitus, and thus might provide a treatment strategy for modifying the natural history of diabetes.