Volume 21, Issue 4 p. 837-843
ORIGINAL ARTICLE

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

Priyathama Vellanki MD

Priyathama Vellanki MD

Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia

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Neda Rasouli MD

Neda Rasouli MD

Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado-Denver, Denver, Colorado

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David Baldwin MD

David Baldwin MD

Division of Endocrinology, Department of Medicine, Rush University Medical Center, Chicago, Illinois

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Sara Alexanian MD

Sara Alexanian MD

Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University, Boston, Massachusetts

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Isabel Anzola MD

Isabel Anzola MD

Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia

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Maria Urrutia MD

Maria Urrutia MD

Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia

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Saumeth Cardona MD

Saumeth Cardona MD

Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia

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Limin Peng PhD

Limin Peng PhD

Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, Georgia

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Francisco J. Pasquel MD

Francisco J. Pasquel MD

Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia

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Guillermo E. Umpierrez MD

Corresponding Author

Guillermo E. Umpierrez MD

Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia

Correspondence

Guillermo E. Umpierrez MD, Department of Medicine, Emory University School of Medicine, 69 Jesse Hill Jr Drive SE, Glenn Building, Suite 202, Atlanta, Georgia 30303.

Email: geumpie@emory.edu

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Linagliptin Inpatient Research Group

Linagliptin Inpatient Research Group

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First published: 20 November 2018
Citations: 52
Funding information This was an investigator-initiated study funded by Boehringer Ingelheim, 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. P. V. was funded in part by K12HD085850; The funding sources were not involved in study design, data collection, interpretation, statistical analysis, manuscript preparation or the decision to submit the manuscript for publication; Boehringer Ingelheim; National Center for Research Resources, Grant/Award Number: 1P30DK111024-01UL1 TR001082UL1RR025008

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.

CONFLICTS OF INTEREST

G. E. U. has received unrestricted research support for inpatient studies (to Emory University) from Merck, Novo Nordisk, AstraZeneca, Boehringer Ingelheim and Sanofi and has received advisory/consulting fees from Sanofi and Merck. P. V. has received consulting fees from Boehringer Ingelheim and Merck. F. J. P. has received consulting fees from Merck, Sanofi and Boehringer Ingelheim. N. R. has received research support from Novo Nordisk, AstraZeneca, Boehringer Ingelheim and Intarcia. The remaining authors have no conflicts of interest.

Author contributions

P.V and G.E.U wrote the first draft of the manuscript. P.V, N.R, D.B, S.A, I.A, M.U, F.J.P and G.E.U were all involved in the conduct of the study. L.P analyzed the data. All authors critically reviewed and edited the manuscript for intellectual content.