Abstract

Background: Cystic Fibrosis-Related Diabetes (CFRD) affects up to 50% of adults with cystic fibrosis and has traditionally been managed with insulin monotherapy according to current guidelines. However, the era of highly effective CFTR modulator therapies has transformed the clinical landscape, improving survival while dramatically increasing the prevalence of overweight and obesity in this population. This fundamental demographic shift from historically underweight patients to increasingly overweight and obese adults challenges conventional CFRD management paradigms and necessitates novel therapeutic approaches focused on concurrent weight management.

Objective: This mini-review examines emerging evidence for novel antidiabetic therapies with weight management benefits, specifically GLP-1 receptor agonists and SGLT2 inhibitors, in overweight and obese adults with CFRD, synthesizing recent case series data with contemporary obesity research to evaluate therapeutic potential for this evolving patient population.

Key findings: Recent case series demonstrate substantial weight reduction outcomes with GLP-1 receptor agonists in overweight and obese CFRD patients, including significant weight loss (median -7.2 kg, BMI reductions up to 8.1 kg/m2), improved glycemic control with a 31.5% reduction in insulin requirements, and unexpected pulmonary function improvements in 73% of patients. SGLT2 inhibitor case series similarly show modest but meaningful weight reduction alongside glycemic management with additional cardiovascular and renal protective effects. Both therapeutic classes demonstrate acceptable safety profiles while addressing the critical need for weight management in this transformed patient population.

Implications: The emergence of overweight and obesity as dominant concerns in adult CFRD patients necessitates a fundamental paradigm shift from traditional weight-promoting approaches toward comprehensive weight management strategies. The convergence of improved CF survival, the obesity epidemic, and effective weight-reducing therapeutic options demands personalized, multi-drug approaches. Randomized controlled trials focusing specifically on weight management outcomes in obese CFRD adults are urgently needed to establish evidence-based protocols for this evolving demographic.

Keywords: Cystic fibrosis-related diabetes; Obesity; Overweight; Weight management; GLP-1 receptor agonists; SGLT2 inhibitors; CFTR modulators; Weight reduction