Chronic incretin-based th...

Patient's age and gender

44 years, male

 

Clinical Presentation

Frequently hospitalized every 3–4 months due to respiratory infections and impaired glucose tolerance.

Clinical history

Cystic fibrosis (CF) of the delF508/delF508 genotype. Long-standing history of pancreatic insufficiency (PI) and receiving pancreatic enzyme replacement therapy (PERT)

 

Physical examination

BMI: 19.1 kg/m²

 

Laboratory examination

Test	Results
Oral glucose tolerance test (OGTT) two months post last CF flare	Fasting blood glucose (FBG): 102 mg/dl 2-hour value: 204 mg/dl
Blood glucose values	30 mins: 256 mg/dl 60 mins: 327 mg/dl 90 mins: 362 mg/dl
HbA1c	6.0%
Average glucose (eAG)	125 mg/dl
Continuous Glucose Monitoring (CGM)	Postprandial hyperglycemia after almost every meal, with occasional low blood glucose levels

 

Diagnosis

Cystic fibrosis-related diabetes

 

 

 

Treatment

The patient was advised to start insulin treatment, but he strongly declined. He also objected to any form of injectable medication or checking his blood glucose using finger sticks. As a result, Sitagliptin 100 mg daily orally was prescribed.

 

Follow-up 1

After 6 months, the CGM blood glucose fluctuations present prior to initiation of therapy were resolved. Two-hour postprandial BG had trended towards normal range, FBG normalized, no hypoglycemia was observed; HbA1c was 5.6%. Excellent glycemic control was sustained. BMI showed a gradual improvement to 19.8 kg/m2

 

Follow-up 2

After 2 years, his lung disease necessitated portable oxygen use, and he underwent a bilateral lung transplant. His glycemic control remained excellent on Sitagliptin even eight years post-transplantation.

Discussion

Sitagliptin is an antidiabetic medication that works by inhibiting dipeptidyl peptidase-4 (DPP-4), an enzyme found on various cell surfaces. This inhibition prevents the breakdown of incretin hormones, including glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), leading to a reduction in high blood sugar levels. In individuals with CF and abnormal glucose metabolism, sitagliptin treatment appears to enhance the body's response to these incretins during meals, resulting in improved early insulin release and suppression of glucagon while not impacting post-meal blood sugar levels or glycated hemoglobin levels. In this particular case, Sitagliptin remained effective over the long term, spanning more than 8 years. Effective glycemic control with Sitagliptin was consistently observed throughout this extended period. Therefore, Sitagliptin therapy can be a valuable approach to managing cystic fibrosis-related diabetes (CFRD). Moreover, it is well-tolerated and does not carry the risk of hypoglycemia.

 

Reference
Sebastián-Valles F, Arranz A, Girón R, Knott-Torcal C, Sampedro‐Núñez M, Jose Carlos Martin-Adan, et al. Continuous Glucose Monitoring as an Additional Tool in Early Cystic Fibrosis-Related Diabetes Monitoring and in the Evaluation of Short-Term Sitagliptin Response. Biomedicines. 2023 Jun 19;11(6):1754.