Sodium Glucose‐Like Co‐Transporter 2 Inhibitor (SGLT2i) Use in Adults With Cystic Fibrosis

ABSTRACT

Sodium‐glucose cotransporter 2 inhibitors (SGLT2i) also called flozins or gliflozins have been demonstrated to have multi‐system benefits across the endocrine, metabolic, renal and cardiovascular systems. As a result, indications for use of SGLT2i have grown, however, there is limited evidence describing their use in people with CF (pwCF). We describe safe, tolerable and effective use of SGLT2i in three adults with CF. Indications for SGLT2i in our three cases varied. Our first case required it for glycaemic management due to predominantly type 2 diabetes phenotype. The next case had heavy proteinuria due to CF diabetes‐related nephropathy. And the last case had non‐diabetes related nephropathy. All cases tolerated SGLT2i without any side effects. Our findings add to the limited literature on SGLT2i use in pwCF, which will become increasingly relevant given an ageing CF population in the post‐modulator era.

Use of sodium glucose‐like co‐transporter 2 inhibitors in people with cystic fibrosis may be considered for glycaemic, renal and cardiac benefits. We described safe, tolerable and effective use in three adults with CF.

1. Introduction

With an ageing cystic fibrosis (CF) population, attention is pivoting to extrapulmonary co‐morbidities including diabetes, renal and cardiovascular disease. Sodium‐glucose cotransporter 2 inhibitors (SGLT2i), also called gliflozins or flozins, are a class of agents that have revolutionised glycaemic, cardiovascular, metabolic and renal management. Their predominant mechanism of action is at the proximal renal tubule where they inhibit glucose reabsorption leading to increased urinary glucose losses [1]. However, they also have diverse and pleomorphic effects. For example, studies in people living with type 2 diabetes have demonstrated a reduction in hospitalisation from heart failure, cardiovascular and renal protection, in addition to their glycaemic benefits [2]. Additionally, they offer modest weight loss/neutrality, improvements in blood pressure and are generally well tolerated. With wide‐ranging multi‐system benefits, SGLT2i have quickly become a core component of therapeutic regimens for many people living with diabetes and/or cardiovascular or renal disease [3, 4, 5].

Despite widespread uptake and use of SGLT2i, evidence on their use in people with CF (pwCF) remains limited with trials still recruiting (NCT06149793). Only one case series comprising eight adults has been published to date highlighting experiences of SGLT2i use in pwCF [6]. Here, we aim to add to the limited literature and share our experiences.

2. Case Series

2.1. Methods

Our adult CF centre at the Prince Charles Hospital in Australia currently provides clinical care for over 360 pwCF and serves a large geographic area comprising regional, rural and remote parts of Queensland, Australia. Our CF Endocrine Service is embedded within the pre‐existing CF multi‐disciplinary team and comprises endocrinology, diabetes education and dietetics. As part of a CF Endocrine service audit, we evaluated use of SGLT2i in pwCF at our centre. Appropriate authorisation for this project was obtained through the Metro North Health and Hospital Services Human Research Ethics Committee (Project ID: 103775; EX/2023/MNHB/103775). The authors declare that written informed consent was obtained for the publication of this manuscript and accompanying images and attest that the form used to obtain consent from the patient(s) complies with the Journal requirements as outlined in the author guidelines. The audit involved database‐driven diagnostics and correlation with pharmacy records to capture all pwCF attending our centre currently or previously prescribed SGLT2i for any indication. The audit was completed in August 2025.

2.2. Results

In total, three [3] pwCF were identified to be initiated on SGLT2i use and currently on continued treatment. Biological sex, genotype, CF modulator use, FEV1, diabetes status, anthropometric data are presented in Table 1.

TABLE 1.

Case study characteristics.

Variable	Case Study 1	Case Study 2	Case Study 3
Demographics	80 M	35 M	40 M
Genotype	Rare mutation	Heterozygous F508del	Homozygous F508del
SGLT2i commenced	June 2023	November 2024	October 2024
Pre‐SGLT2i FEV1 (litres / % predicted)	0.84 L / 32%	1.29 L / 28.4%	2.39 L / 59.7%
Most recent FEV1 (on SGLT2i) (litres / % predicted)	0.90 L / 34%	1.21 L / 26.7%	1.94 L / 48.4%
Diabetes status	Type 2 diabetes diagnosed	CF‐diabetes insulin requiring since 2014	No history of diabetes
BMI kg/m 2	22.5	17.53	28.3
CFTR Modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI)	ETI since July 2025	ETI since 2019 with intermittent breaks due to liver derangements	Continuous ETI since June 2022
Pre‐ETI modulator use	Not eligible	Nil	Ivacaftor since 2014
Sputum rheology	Previous to ETI & SGLT2i sputum was variable between yellow moderate viscosity to purulent green. Post‐ETI sputum thinner, lighter colour and decreased in volume.	Consistently has moderate viscosity, light green sputum with no discernible change with ETI or SGLT2i	No regular production of sputum available for assessment.
Sputum microbiology	Prior positivity for Pseudomonas aeruginosa and Staphylococcus aureus	Current positivity for Pseudomonas aeruginosa and Staphylococcus aureus	Prior positivity for Pseudomonas aeruginosa

Indications for SGLT2i initiation varied among the identified three cases. One case had a history of type 2 diabetes exacerbated by a long history of glucocorticoid use. He commenced oral anti‐hyperglycaemic therapy under supervision of CF Endocrine service which initially comprised Metformin 1 g daily and a dipeptidyl peptide peptidase inhibitors (DPP4i) sitagliptin 100 mg daily. Subsequently, gliclazide 30 mg daily was added to reach glycaemic targets. On this diabetes regimen his HbA1c remained within an individualised target range of 7.5%–8.0%. In late 2022, he experienced three hospitalisations for pulmonary exacerbations over a six‐month period which was associated with up titrated doses of glucocorticoids. This led to significant deterioration in his glycaemia with HbA1c peaking at 10.6%. His preference was to avoid insulin due to risk of hypoglycaemia, which aligned with his care team's concerns given his age and history of recurrent falls. The CF Endocrine team commenced SGLT2i (empagliflozin 10 mg) for glycaemic management in June 2023 and ceased the DPP4i in the context of mild pancreatitis. Empagliflozin was well‐tolerated and consistently continued for over two years. During this time, he had reduced frequency of hospitalisations and was able to be maintained on 8 mg daily dose of prednisolone, which had been unsuccessful to wean. With initiation of SGLT2i, his diabetes management was also optimised with his HbA1c subsequently returning to his individualised target range (see Figure 2). He continues on SGLT2i to‐date.

FIGURE 2.

Change in HbA1c with SGLT2i initiation. Change in glycaemia with initiation of SGLT2i in case study 1 (green line) and case study 2 (blue line) showing differing trajectories.

The other two cases were commenced on SGLT2i for management of chronic kidney disease and associated proteinuria. One case had a longstanding history of CF‐related diabetes requiring insulin with chronic hyperglycaemia (HbA1c persistently > 9% for over 10 years). He experienced frequent pulmonary exacerbations, even whilst on ETI which were associated with acute kidney injury. He was found to have nephrotic range proteinuria on screening and associated renal decline. He was commenced on SGLT2i in consultation with endocrinology, nephrology and CF physicians in November 2024 (dapagliflozin 10 mg daily) and ramipril 2.5 mg daily. Despite reported SGLT2i, ETI and ramipril adherence, his proteinuria did not improve (Figure 1). However, his eGFR did increment from a nadir of 40 mL/min/1.73 m2 to 77 mL/min/1.73 m2. With regards to glycaemia his HbA1c fluctuated between 7.9% and 11.9%, with psychosocial factors significantly impacting self‐management of diabetes (see Figure 2). He remained normotensive throughout, at times requiring down‐titration of his ramipril due to symptoms of postural hypotension. To date, he continues on SGLT2i.

FIGURE 1.

Change in proteinuria with SGLT2i. Change in proteinuria with initiation of SGLT2i in case study 2 (blue line) and case study 3 (red line) showing differing trajectories.

The last case had chronic kidney disease secondary to post‐infectious glomerulonephritis, unrelated to his cystic fibrosis. He did not have a history of diabetes. His eGFR was noted to decline over time to a nadir of 40 mL/min/1.73 m2 in February 2024, at which time a renal biopsy elucidated his renal diagnosis. Subsequently in October 2024, he was commenced on dapagliflozin 10 mg together with irbesartan 150 mg daily. His proteinuria significantly improved and he has remained normotensive throughout (Figure 1) and continues on SGLT2i without any issues.

Nutritional parameters including fat soluble vitamin levels and body mass index were noted to be stable for all cases. Bone mineral density continues to be monitored with no overt decline or fracture capture.

3. Discussion

Our centre audit found three pwCF were using SGTL2i for differing indications with variable responses. Our cases were treated continuously with SGLT2i for over six months with view to continued therapy. Specifically, none of the cases reported genitourinary infections, urinary frequency or other metabolic derangements with SGLT2i use. Nutritional parameters including fat soluble vitamin levels and body mass index were also noted to be stable. Pulmonary function remained unchanged with SGLT2i commencement.

Compared to the only other case series published by Moheet and colleagues reporting SGLT2i use in pwCF [6], only one of our three cases was co‐administered SGLT2i with insulin. Despite reported adherence, the SGLT2i had variable impact on glycaemia, with no change in total daily insulin requirements and proteinuria. This aligns with their findings where a quarter of their cases (2/8) did not demonstrate improvements in glycaemia or reduction in insulin requirements. It remains unclear whether renal impairment observed in our case reduced glycaemic benefit through proximal tubule mechanisms or this reflects inter‐individual variability in drug response.

In contrast to the study published by Moheet and colleagues [6], two pwCF in our series did not have CF‐related diabetes. Indications for SGLT2i initiation in these cases aligned with evidence‐based practice guidelines for type 2 diabetes [3] and proteinuria without diabetes [4]. Communication across disciplines and with the CF care team ensured there were no significant drug–drug interactions. Subsidised access to SGLT2i was sought to avoid out‐of‐pocket expenses for the patients and this facilitated continued treatment. In both of these cases, therapeutic efficacy was demonstrated with improvement in glycaemic management and urinary protein losses, respectively. These findings have important clinical implications given an ageing CF population who may meet cardiovascular and/or renal indications for use of these therapies in the absence of CF‐related diabetes. Finally, there was no notable change in pulmonary function and sputum rheology with initiation of SGLT2i in our cases; however, their potential impact on pulmonary outcomes in non‐CF conditions continue to be explored [7, 8, 9].

In conclusion, we present and discuss data from three pwCF who continue safely on long‐term SGLT2i for glycaemic and renal indications. Our findings add to the limited literature on long‐term use of SGLT2i in pwCF. Clinicians caring for pwCF should carefully consider the potential risk of SGLT2i against their robust evidence‐based benefits for diabetes, renal, and cardiac management to prevent unwarranted exclusion of the CF population.

Author Contributions

E.J.: writing of first draft, data collection, A.M.: data collection, review, and editing. S.K.: conceptualisation, review and editing, supervision.

Funding

The authors have nothing to report.

Ethics Statement

The authors declare that they have obtained appropriate authorisation to access and publish the patients' data from: Institution review board or Ethics committee name: Metro North Hospital and Health Services. Authorisation number: Project ID: 103775; EX/2023/MNHB/103775.

Conflicts of Interest

The authors declare no conflicts of interest.

Johnson E., Matson A., Cobb R., and Kumar S., “Sodium Glucose‐Like Co‐Transporter 2 Inhibitor (SGLT2i) Use in Adults With Cystic Fibrosis,” Respirology Case Reports 14, no. 3 (2026): e70533, 10.1002/rcr2.70533.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.