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

Diabetes Obes Metab. 2018 May;20(5):1121-1130. doi: 10.1111/dom.13196. Epub 2018 Jan 22.

Abstract

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.

Keywords: Korea; blood glucose; combination; drug therapy; glimepiride; hyperglycaemia; hypoglycaemic agents; insulin glargine; insulin glulisine; type 2 diabetes mellitus.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Resistance, Multiple
  • Drug Therapy, Combination / adverse effects
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / analysis
  • Hospitals, University
  • Humans
  • Hyperglycemia / prevention & control*
  • Hypoglycemia / prevention & control*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Insulin / therapeutic use*
  • Insulin Resistance
  • Insulin Secretion / drug effects
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Male
  • Metformin / administration & dosage
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Middle Aged
  • Outpatient Clinics, Hospital
  • Republic of Korea
  • Sulfonylurea Compounds / administration & dosage
  • Sulfonylurea Compounds / adverse effects
  • Sulfonylurea Compounds / therapeutic use*

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • hemoglobin A1c protein, human
  • glimepiride
  • Metformin