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

• Type of Material: Article
• Authors: Priyathama Vellanki, Emory University; Neda Rasouli, University of Colorado; David Baldwin, Rush University; Sara Alexanian, Boston University; Isabel Anzola, Emory University; Maria Urrutia, Emory University; Saumeth Cardona, Emory University; Limin Peng, Emory University; Francisco Pasquel, Emory University; Guillermo Umpierrez, Emory University; J Haw, Emory University; Maya Fayfman, Emory University
• Language: English
• Date: 2019-04-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 John Wiley & Sons Ltd
• Final Published Version (URL): http://dx.doi.org/10.1111/dom.13587
• Title of Journal or Parent Work: Diabetes Obesity & Metabolism
• Volume: 21
• Issue: 4
• Start Page: 837
• End Page: 843
• Grant/Funding Information: This was an investigator-initiated study funded by Boehringer Ingelheim and Atlanta and Colorado CTSA grants, Public Health Service Grant UL1 RR025008 and UL1 TR001082 from the Clinical and Translational Science Award program, and 1P30DK111024-01 from the National Institutes of Health and National Center for Research Resources.; PV was funded in part by K12HD085850.
• Keywords: Life Sciences & Biomedicine; Mortality; Glucose control; Endocrinology & Metabolism; Hospitalized patients; randomised trial; Critically ill; glycaemic control; Science & Technology; Infection; Inpatient management; General medicine; DPP-IV inhibitor; Sitagliptin; Therapy; incretin therapy; Hyperglycemia
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Public Health; Biology, Biostatistics

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.