Long‐term effects on glycaemic control and β‐cell preservation of early intensive treatment in patients with newly diagnosed type 2 diabetes: A multicentre randomized trial

Aim To determine the effects of early intensive glycaemic control with intensive insulin treatment (IIT) or initial combined oral antidiabetic drug (COAD) therapy on long‐term glycaemic control and the preservation of β‐cell function in people with type 2 diabetes mellitus (T2DM). Methods Newly diagnosed drug‐naïve patients with T2DM from 8 outpatient diabetes centres were randomized to receive either IIT ( n = 50; glargine/glulisine) or COAD ( n = 47; glimepiride/metformin) as intensive treatment until the termination criteria to ensure euglycaemia were met. After intensive treatment, the patients completed a follow‐up period with either lifestyle modification (LSM) alone or rescue therapy to maintain target glycated haemoglobin levels of <7% (53 mmol/mol) up to week 104. The primary outcomes were analysed after excluding participants who were anti‐glutamic acid decarboxylase autoantibody‐positive. Results Both intensive treatment methods were effective for short‐term glycaemic control, but improvements in the disposition index (DI) were significantly greater in the IIT group than in the COAD group ( P = .021). During the follow‐up period after intensive treatment, the two groups significantly differed in rescue method regarding the maintenance of comparable levels of glycaemic control ( P = .010) and more participants who received IIT exhibited well‐controlled glycaemia with LSM alone. Additionally, the IIT group maintained a higher DI than the COAD group during the follow‐up period. Cox regression analysis showed that the IIT method was associated with a 52.5% lower risk of failing to maintain drug‐free glycaemic remission compared with the COAD method ( P = .015). Conclusions The findings indicate that outpatient clinic‐based IIT to ensure euglycaemia in newly diagnosed patients with T2DM might be an effective initial therapeutic option for improvements in β‐cell function and glycaemic control over the long term, without serious adverse events.