Glucagon-like Peptide1 Receptor Agonist Treatment of Cystic Fibrosis-related Diabetes Complicated by Obesity: A Cases Series and Literature Review

Overview

Journal J Clin Transl Endocrinol

Specialty Endocrinology

Date 2025 Jan 7

PMID 39764279

Authors

Ammar Ahmed

Anvitha Ankireddypalli

Tasma Harindhanavudhi

Antoinette Moran

Amir Moheet

Affiliations

Soon will be listed here.

Abstract

Cystic fibrosis-related diabetes (CFRD) is the most common non-pulmonary comorbidity in people with cystic fibrosis (CF). Current guidelines recommend insulin therapy as the treatment of choice for people with CFRD. In the past, obesity and overweight were uncommon in individuals with CF. However, in recent years, advancements in CF therapies have led to a significant increase in the prevalence of overweight and obesity within this population. Glucagon-like peptide1 receptor agonist (GLP-1 RA) therapies could potentially improve glycemic control in people with CF by increasing insulin secretion, slowing gastric emptying, and promoting weight loss through central appetite suppression, which in turn can enhance insulin sensitivity. We report, for the first time, five cases of individuals with CFRD complicated by obesity treated with GLP 1-RA for at least two years. With GLP 1-RA therapy, 4 out of 5 individuals exhibited weight reduction ranging from 7% to 19% over two years, while forced expiratory volume in 1 s (FEV1)/predicted FEV1 % remained stable or improved in all cases. The impact on glycemic control was variable. Insulin requirements either reduced or remained stable in all five cases. Overall, GLP-1 RA was well tolerated in this case series; one individual discontinued the medication after two years of therapy due to poor appetite and nausea.

References

Holst J . Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005. Diabetologia. 2006; 49(2):253-60. DOI: 10.1007/s00125-005-0107-1. View

Culhane S, George C, Pearo B, Spoede E . Malnutrition in cystic fibrosis: a review. Nutr Clin Pract. 2013; 28(6):676-83. DOI: 10.1177/0884533613507086. View

Holt M, Richards J, Cook D, Brierley D, Williams D, Reimann F . Preproglucagon Neurons in the Nucleus of the Solitary Tract Are the Main Source of Brain GLP-1, Mediate Stress-Induced Hypophagia, and Limit Unusually Large Intakes of Food. Diabetes. 2018; 68(1):21-33. PMC: 6314470. DOI: 10.2337/db18-0729. View

. Standards of medical care in diabetes--2009. Diabetes Care. 2009; 32 Suppl 1:S13-61. PMC: 2613589. DOI: 10.2337/dc09-S013. View

Petersen M, Begnel L, Wallendorf M, Litvin M . Effect of elexacaftor-tezacaftor-ivacaftor on body weight and metabolic parameters in adults with cystic fibrosis. J Cyst Fibros. 2021; 21(2):265-271. PMC: 9999463. DOI: 10.1016/j.jcf.2021.11.012. View

Geyer M, Sullivan T, Tai A, Morton J, Edwards S, Martin A . Exenatide corrects postprandial hyperglycaemia in young people with cystic fibrosis and impaired glucose tolerance: A randomized crossover trial. Diabetes Obes Metab. 2018; 21(3):700-704. DOI: 10.1111/dom.13544. View

Hillman M, Eriksson L, Mared L, Helgesson K, Landin-Olsson M . Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus. J Cyst Fibros. 2011; 11(2):144-9. DOI: 10.1016/j.jcf.2011.11.001. View

Gray M, Winpenny J, Verdon B, McAlroy H, Argent B . Chloride channels and cystic fibrosis of the pancreas. Biosci Rep. 1995; 15(6):531-41. DOI: 10.1007/BF01204355. View

Bailey J, Rozga M, McDonald C, Bowser E, Farnham K, Mangus M . Effect of CFTR Modulators on Anthropometric Parameters in Individuals with Cystic Fibrosis: An Evidence Analysis Center Systematic Review. J Acad Nutr Diet. 2020; 121(7):1364-1378.e2. DOI: 10.1016/j.jand.2020.03.014. View

10.

Kastner-Cole D, Palmer C, Ogston S, Mehta A, Mukhopadhyay S . Overweight and obesity in deltaF508 homozygous cystic fibrosis. J Pediatr. 2005; 147(3):402-4. DOI: 10.1016/j.jpeds.2005.06.003. View

11.

Stephenson A, Mannik L, Walsh S, Brotherwood M, Robert R, Darling P . Longitudinal trends in nutritional status and the relation between lung function and BMI in cystic fibrosis: a population-based cohort study. Am J Clin Nutr. 2013; 97(4):872-7. DOI: 10.3945/ajcn.112.051409. View

12.

Volkova N, Moy K, Evans J, Campbell D, Tian S, Simard C . Disease progression in patients with cystic fibrosis treated with ivacaftor: Data from national US and UK registries. J Cyst Fibros. 2019; 19(1):68-79. DOI: 10.1016/j.jcf.2019.05.015. View

13.

Nauck M, Petrie J, Sesti G, Mannucci E, Courreges J, Lindegaard M . A Phase 2, Randomized, Dose-Finding Study of the Novel Once-Weekly Human GLP-1 Analog, Semaglutide, Compared With Placebo and Open-Label Liraglutide in Patients With Type 2 Diabetes. Diabetes Care. 2015; 39(2):231-41. DOI: 10.2337/dc15-0165. View

14.

Coderre L, Debieche L, Plourde J, Rabasa-Lhoret R, Lesage S . The Potential Causes of Cystic Fibrosis-Related Diabetes. Front Endocrinol (Lausanne). 2021; 12:702823. PMC: 8361832. DOI: 10.3389/fendo.2021.702823. View

15.

Litvin M, Yoon J . Nutritional excess in cystic fibrosis: the skinny on obesity. J Cyst Fibros. 2019; 19(1):3-5. DOI: 10.1016/j.jcf.2019.12.002. View

16.

Schirra J, Katschinski M, Weidmann C, Schafer T, Wank U, Arnold R . Gastric emptying and release of incretin hormones after glucose ingestion in humans. J Clin Invest. 1996; 97(1):92-103. PMC: 507066. DOI: 10.1172/JCI118411. View

17.

Stallings V, Stark L, Robinson K, Feranchak A, Quinton H . Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. J Am Diet Assoc. 2008; 108(5):832-9. DOI: 10.1016/j.jada.2008.02.020. View

18.

Borowitz D, Baker R, Stallings V . Consensus report on nutrition for pediatric patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2002; 35(3):246-59. DOI: 10.1097/00005176-200209000-00004. View

19.

Nauck M, Quast D, Wefers J, Meier J . GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art. Mol Metab. 2020; 46:101102. PMC: 8085572. DOI: 10.1016/j.molmet.2020.101102. View

20.

Gnanapragasam H, Mustafa N, Bierbrauer M, Andrea Providence T, Dandona P . Semaglutide in Cystic Fibrosis-Related Diabetes. J Clin Endocrinol Metab. 2020; 105(7). DOI: 10.1210/clinem/dgaa167. View