Glycaemic efficacy and safety of linagliptin compared to a basal-bolus insulin regimen in patients with type 2 diabetes undergoing non-cardiac surgery: A multicentre randomized clinical trial

Diabetes Obes Metab. 2019 Apr;21(4):837-843. doi: 10.1111/dom.13587. Epub 2018 Dec 17.

Abstract

Aims: The use of incretin-based therapy, rather than or complementary to, insulin therapy is an active area of research in hospitalized patients with type 2 diabetes (T2D). We determined the glycaemic efficacy and safety of linagliptin compared to a basal-bolus insulin regimen in hospitalized surgical patients with T2D.

Materials and methods: This prospective open-label multicentre study randomized T2D patients undergoing non-cardiac surgery with admission blood glucose (BG) of 7.8 to 22.2 mmol/L who were under treatment with diet, oral agents or total insulin dose (TDD) ≤ 0.5 units/kg/day to either linagliptin (n = 128) daily or basal-bolus (n = 122) with glargine once daily and rapid-acting insulin before meals. Both groups received supplemental insulin for BG > 7.8 mmol/L. The primary endpoint was difference in mean daily BG between groups.

Results: Mean daily BG was higher in the linagliptin group compared to the basal-bolus group (9.5 ± 2.6 vs 8.8 ± 2.3 mmol/L/dL, P = 0.03) with a mean daily BG difference of 0.6 mmol/L (95% confidence interval 0.04, 1.2). In patients with randomization BG < 11.1 mmol/L (63% of cohort), mean daily BG was similar in the linagliptin and basal-bolus groups (8.9 ± 2.3 vs 8.7 ± 2.3 mmol/L, P = 0.43); however, patients with BG ≥ 11.1 mmol/L who were treated with linagliptin had higher BG compared to the basal-bolus group (10.9 ± 2.6 vs 9.2 ± 2.2 mmol/L, P < 0.001). Linagliptin resulted in fewer hypoglycaemic events (1.6% vs 11%, P = 0.001; 86% relative risk reduction), with similar supplemental insulin and fewer daily insulin injections (2.0 ± 3.3 vs 3.1 ± 3.3, P < 0.001) compared to the basal-bolus group.

Conclusions: For patients with T2D undergoing non-cardiac surgery who presented with mild to moderate hyperglycaemia (BG < 11.1 mmol/L), daily linagliptin is a safe and effective alternative to multi-dose insulin therapy, resulting in similar glucose control with lower hypoglycaemia.

Keywords: DPP-IV inhibitor; glycaemic control; incretin therapy; randomised trial.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amputation
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Digestive System Surgical Procedures
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Female
  • Glycated Hemoglobin A / metabolism
  • Gynecologic Surgical Procedures
  • Hospitalization
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use
  • Insulin Glargine / therapeutic use*
  • Insulin, Short-Acting / therapeutic use*
  • Linagliptin / therapeutic use*
  • Male
  • Middle Aged
  • Orthopedic Procedures
  • Perioperative Care / methods*
  • Surgical Procedures, Operative*
  • Treatment Outcome
  • Urologic Surgical Procedures

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Insulin, Short-Acting
  • hemoglobin A1c protein, human
  • Insulin Glargine
  • Linagliptin