Sitagliptin-induced hyperthyroidism: a case report

Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is commonly used to manage type 2 diabetes mellitus (T2DM). Although generally considered safe, recent studies suggest a potential role of DPP-4 inhibitors in modulating immune responses, potentially leading to autoimmune conditions, including thyroid dysfunction. This case report aims to investigate the potential association between sitagliptin use and hyperthyroidism, emphasizing the significance of regular thyroid function monitoring in patients treated with DPP-4 inhibitors. A 54-year-old man with a history of hypertension and a family history of diabetes and hypothyroidism was initiated on sitagliptin and metformin for diabetes (HbA1c=8.1%) with normal thyroid function. Three months after initiating treatment, the patient noted weight loss and other initial symptoms of hyperthyroidism; however, nine months later, the patient developed full symptoms of hyperthyroidism, including significant weight loss, palpitations, tremors, and fatigue. Laboratory findings confirmed elevated total T3 (260 ng/dL) and total T4 (20 µg/dL) levels, suppressed TSH (<0.05 µIU/mL) levels, and increased anti-thyroid peroxidase (anti-TPO) antibodies (548 IU/mL). Although thyroid-stimulating hormone receptor antibody (TRAb) testing, ultrasonography, and scintigraphy were not performed, the temporal relationship between sitagliptin initiation and symptom onset, followed by resolution upon drug discontinuation, strongly suggests a probable association. Sitagliptin was discontinued, and Carbimazole was initiated, resulting in clinical and biochemical im­provement. The patient’s thyroid function normalized within six months, further supporting the association between sitagliptin and hyperthyroidism. Carbimazole was continued for 15-months resulting in Hb1Ac (6.6%), total T3 (140 ng/dL), total T4 (8.85 µg/dL), and TSH (1.81 µIU/mL) levels. Five months after discontinuation of Carbimazole, laboratory investigations revealed HbA1c (6.6%), fasting blood glucose (112.33 mg/dL), vitamin D (29.7 ng/mL), vitamin B12 (231 pg/mL), total T3 (151 ng/dL), total T4 (9.84 µg/dL), and TSH (1.18 µIU/mL) levels. In conclusion, this case suggests a potential association between sitagliptin and hyperthyroidism, possibly via immunomodulation. While routine thyroid function monitoring in patients on DPP-4 inhibitors may be considered, larger studies are needed to confirm this association.