Management of type 2 diabetes in patients with compensated liver cirrhosis: Short of evidence, plenty of potential

Konstantinos Arvanitakis; Theocharis Koufakis; Georgios Kalopitas; Stavros P Papadakos; Kalliopi Kotsa; Georgios Germanidis

doi:10.1016/j.dsx.2023.102935

Management of type 2 diabetes in patients with compensated liver cirrhosis: Short of evidence, plenty of potential

Diabetes Metab Syndr. 2024 Jan;18(1):102935. doi: 10.1016/j.dsx.2023.102935. Epub 2023 Dec 28.

Authors

Konstantinos Arvanitakis¹, Theocharis Koufakis², Georgios Kalopitas¹, Stavros P Papadakos³, Kalliopi Kotsa⁴, Georgios Germanidis⁵

Affiliations

¹ Division of Gastroenterology and Hepatology, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636, Thessaloniki, Greece; Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636, Thessaloniki, Greece.
² Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642, Thessaloniki, Greece.
³ First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
⁴ Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636, Thessaloniki, Greece.
⁵ Division of Gastroenterology and Hepatology, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636, Thessaloniki, Greece; Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636, Thessaloniki, Greece. Electronic address: geogerm@auth.gr.

PMID: 38163417
DOI: 10.1016/j.dsx.2023.102935

Abstract

Background and aims: Treatment of type 2 diabetes (T2D) in patients with compensated cirrhosis is challenging due to hypoglycemic risk, altered pharmacokinetics, and the lack of robust evidence on the risk/benefit ratio of various drugs. Suboptimal glycemic control accelerates the progression of cirrhosis, while the frequent coexistence of nonalcoholic fatty liver disease (NAFLD) with T2D highlights the need for a multifactorial therapeutic approach.

Methods: A literature search was performed in Medline, Google Scholar and Scopus databases till July 2023, using relevant keywords to extract studies regarding the management of T2D in patients with compensated cirrhosis.

Results: Metformin, sodium-glucose co-transporter-2 inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA) are promising treatment options for patients with T2D and compensated liver cirrhosis, offering good glycemic control with minimal risk of hypoglycemia, while their pleiotropic actions confer benefits on NAFLD and body weight, and decrease cardiorenal risk. Sulfonylureas cause hypoglycemia, thus should be avoided, while in specific studies, dipeptidyl peptidase-4 inhibitors have been correlated with increased risk of decompensation and variceal bleeding. Despite the benefits of thiazolidinediones in nonalcoholic steatohepatitis, concerns about edema and weight gain limit their use in compensated cirrhosis. Insulin does not exert hepatotoxic effects and can be administered safely in combination with other drugs; however, the risk of hypoglycemia should be considered.

Conclusions: The introduction of new hepatoprotective diabetes drugs into clinical practice, including tirzepatide, SGLT2i, and GLP-1 RA, sets the stage for future trials to investigate the ideal therapeutic regimen for people with T2D and compensated cirrhosis.

Keywords: Compensated cirrhosis; NASH; Pharmacotherapy; Type 2 diabetes.

Publication types

Review

MeSH terms

Diabetes Mellitus, Type 2* / chemically induced
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / drug therapy
Esophageal and Gastric Varices* / chemically induced
Esophageal and Gastric Varices* / complications
Esophageal and Gastric Varices* / drug therapy
Gastrointestinal Hemorrhage / chemically induced
Gastrointestinal Hemorrhage / complications
Gastrointestinal Hemorrhage / drug therapy
Glucagon-Like Peptide 1
Glucagon-Like Peptide-1 Receptor
Humans
Hypoglycemia* / chemically induced
Hypoglycemic Agents / therapeutic use
Liver Cirrhosis / complications
Liver Cirrhosis / drug therapy
Non-alcoholic Fatty Liver Disease* / complications
Non-alcoholic Fatty Liver Disease* / drug therapy
Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

Hypoglycemic Agents
Sodium-Glucose Transporter 2 Inhibitors
Glucagon-Like Peptide 1
Glucagon-Like Peptide-1 Receptor