Purpose: Dulaglutide, a long acting GLP-1 receptor agonist (GLP-1 RA) is reported to reduce decline in eGFR in patients with diabetic kidney disease (DKD). Dulaglutide has been applied to the treatment and prevention of advanced DKD. GLP-1RA is well known to suppress glucagon secretion from the pancreas. In advanced DKD, renal gluconeogenesis is reduced due to the progression of DKD, and thereby the incidence of hypoglycemia is increased in advanced DKD. However, hypoglycemia due to GLP-1RA is rarely reported in advanced DKD. The present study was performed in order to get further insight into the risk management of hypoglycemia in advanced DKD patients treated with GLP-RA using continuous glucose monitoring (CGM).

Methods: Eleven patients with advanced DKD (eGFR<45) were included in the present study. Whole patients were treated with dulaglutide over 1 year and no other hypoglycemic agents were administered. Two weeks CGM was performed using Free Style Libre Pro. In the case of nocturnal hypoglycemia, the effect of oral administration of medium-chain triglyceride (MCT), which directly stimulates hepatic glucose production, was studied.

Results: Two weeks CGM revealed that asymptomatic nocturnal and persistent hypoglycemia lasting 4 to 6 hours occurred in patients with advanced DKD during dulaglutide monotherapy. Late evening oral administration of a small amount (10-15g) of MCT is effective to avoid dulaglutide-induced nocturnal and persistent hypoglycemia.

Discussion: Dulaglutide-induced nocturnal hypoglycemia in advanced DKD may be attributed to reduced hepatic glycogenolysis and renal gluconeogenesis.

Conclusion: The present study firstly demonstrated that dulaglutide produced asymptomatic nocturnal and persistent hypoglycemia in patients with advanced DKD, which can be prevented by the administration of MCT. CGM is essential for early detection and prevention of dulaglutide-induced hypoglycemia.


H. Nishihara: None. M. Inoue: None. J. Umezu: None. K. Arai: None. T. Sudo: None. J. Sasaki: None. C. Koizumi: None. M. Saito: None. H. Sunagawa: None. A. Hirai: None.

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