Glucagon-like peptide 1 receptor agonists in end-staged kidney disease and kidney transplantation: A narrative review

Kristin K Clemens; Jaclyn Ernst; Tayyab Khan; Sonja Reichert; Qasim Khan; Heather LaPier; Michael Chiu; Saverio Stranges; Gurleen Sahi; Fabio Castrillon-Ramirez; Louise Moist; OK TRANSPLANT Investigators

doi:10.1016/j.numecd.2023.03.023

Glucagon-like peptide 1 receptor agonists in end-staged kidney disease and kidney transplantation: A narrative review

Nutr Metab Cardiovasc Dis. 2023 Jun;33(6):1111-1120. doi: 10.1016/j.numecd.2023.03.023. Epub 2023 Apr 5.

Authors

Affiliations

¹ Department of Medicine, Division of Endocrinology and Metabolism, Western University, 268 Grosvenor Street, N6A 4V2, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, 1465 Richmond Street, N6G 2M1, London, Ontario, Canada; Centre for Diabetes, Endocrinology and Metabolism, St. Joseph's Health Care London, 268 Grosvenor Street, N6A 4V2, London, Ontario, Canada; ICES Western, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada; Lawson Health Research Institute, 750 Base Line Road East, Suite 300, N6C 2R5, London, Ontario, Canada; Department of Medicine, Western University, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada. Electronic address: kristin.clemens@sjhc.london.on.ca.
² Department of Medicine, Western University, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada.
³ Department of Medicine, Division of Endocrinology and Metabolism, Western University, 268 Grosvenor Street, N6A 4V2, London, Ontario, Canada; Centre for Diabetes, Endocrinology and Metabolism, St. Joseph's Health Care London, 268 Grosvenor Street, N6A 4V2, London, Ontario, Canada.
⁴ Department of Family Medicine, Western University, 1465 Richmond Street, N6G 2M1, London, Ontario, Canada.
⁵ Department of Medicine, Division of Gastroenterology, Western University, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada.
⁶ Centre for Diabetes, Endocrinology and Metabolism, St. Joseph's Health Care London, 268 Grosvenor Street, N6A 4V2, London, Ontario, Canada.
⁷ Department of Medicine, Division of Nephrology, Western University, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada.
⁸ Department of Epidemiology and Biostatistics, Western University, 1465 Richmond Street, N6G 2M1, London, Ontario, Canada; Department of Medicine, Western University, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada; Department of Family Medicine, Western University, 1465 Richmond Street, N6G 2M1, London, Ontario, Canada.
⁹ Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street, N6A 5C1, London, Ontario, Canada.
¹⁰ Department of Epidemiology and Biostatistics, Western University, 1465 Richmond Street, N6G 2M1, London, Ontario, Canada; Lawson Health Research Institute, 750 Base Line Road East, Suite 300, N6C 2R5, London, Ontario, Canada; Department of Medicine, Division of Nephrology, Western University, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada.

PMID: 37100640
DOI: 10.1016/j.numecd.2023.03.023

Abstract

Aims: Glucagon-like peptide 1 receptor agonists (GLP-1RA) improve glycemic control and promote weight loss in type 2 diabetes (DM2) and obesity. We identified studies describing the metabolic benefits of GLP-1RA in end-staged kidney disease (ESKD) and kidney transplantation.

Data synthesis: We searched for randomized controlled trials (RCTs) and observational studies that investigated the metabolic benefits of GLP-1RA in ESKD and kidney transplantation. We summarized the effect of GLP-1RA on measures of obesity and glycemic control, examined adverse events, and explored adherence with therapy. In small RCTs of patients with DM2 on dialysis, liraglutide for up to 12 weeks lowered HbA1c by 0.8%, reduced time in hyperglycemia by ∼2%, lowered blood glucose by 2 mmol/L and reduced weight by 1-2 kg, compared with placebo. In prospective studies inclusive of ESKD, 12 months of semaglutide reduced HbA1c by 0.8%, and contributed to weight losses of 8 kg. In retrospective cohort studies in DM2 and kidney transplantation, 12 months of GLP-1RA lowered HbA1c by 2%, and fasting glucose by ∼3 mmol/L compared with non-use, and in some reports, weight losses of up to 4 kg were described. Gastrointestinal (GI) side effects were most commonly reported, with hypoglycemia described with GLP-1RA in hemodialysis, particularly in those using insulin.

Conclusions: GLP-1RA are growing in popularity in those with DM2 and obesity. In small RCTs and observational cohort studies modest glycemic and weight benefits have been described in ESKD and transplantation, but GI side effects may limit adherence. Larger and longer term studies of GLP-1RA remain important.

Keywords: Blood glucose; Diabetes mellitus; End stage kidney disease; Glucagon like peptide 1 receptor; Hemoglobin A1c; Kidney transplantation.

Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2* / diagnosis
Diabetes Mellitus, Type 2* / drug therapy
Glucagon-Like Peptide-1 Receptor / agonists
Glycated Hemoglobin
Humans
Hypoglycemic Agents / adverse effects
Kidney Failure, Chronic* / diagnosis
Kidney Failure, Chronic* / surgery
Kidney Transplantation* / adverse effects
Liraglutide / adverse effects
Obesity / drug therapy
Weight Loss

Substances

Hypoglycemic Agents
Glycated Hemoglobin
Liraglutide
Glucagon-Like Peptide-1 Receptor

Grants and funding

CIHR/Canada