Objective: Type 2 diabetes mellitus (T2DM) is generally regarded as an irreversible chronic condition. As a very low calorie diet (VLCD) can bring about acute return to normal glucose control in some people with T2DM, this study tested the potential durability of this normalization. The underlying mechanisms were defined. Research Design and Methods: People with T2DM duration 0.5-23 years (n=30) followed a VLCD for 8 weeks. All oral agents or insulins were stopped at baseline. Following stepped return to isocaloric diet, a structured, individualized program of weight maintenance was provided. Glucose control, insulin sensitivity, insulin secretion, hepatic and pancreas fat content were quantified at baseline, after return to isocaloric diet and after 6 months to permit the primary comparison of change between post-weight loss and 6 months in responders. Responders were defined as achieving fasting blood glucose <7mmol/l after return to isocaloric diet. Results: Weight fell (98.0±2.6 to 83.8±2.4 kg) and remained stable over 6 months (84.7±2.5 kg). 12/30 achieved fasting plasma glucose <7mmol/l following return to isocaloric diet (responders), and 13/30 after 6 months. Responders had shorter duration diabetes and higher initial fasting plasma insulin level. HbA1c fell from 7.1±0.3 to 5.8±0.2% (55±4 to 40±2mmol/mol) in responders (p<0.001), and from 8.4±0.3 to 8.0±0.5% (68±3 to 64±5mmol/mol) in non-responders, remaining constant at 6 months (5.9±0.2 and 7.8±0.3%; 41±2 and 62±3 mmol/mol respectively). The responders were characterized by return of first phase insulin response. Conclusions: A robust and sustainable weight loss program achieved continuing remission of diabetes for at least 6 months in the 40% who responded to a VLCD by achieving fasting plasma glucose of <7mmol/l. T2DM is a potentially reversible condition.