Objective: This study was conducted to characterize differences in clinical background between patients with and without increased glucagon secretion while on SGLT2 inhibitors (S).

Methods: Of the 75 type 2 diabetic patients admitted for glycemic control who were not receiving incretin-related drugs nor S at admission, 22 patients received S but no incretin-related drugs after admission and were subjected to meal tolerance tests (MTTs) during early morning fasting hours at admission and after improving glycemic control. Blood samples were drawn from these patients preprandially and 30, 60, and 120 minutes postprandially to measure their glucose, C-peptide, and glucagon (Mercodia) values. First, based on changes in glucagon secretion observed in MTTs, they were divided into those with increased AUC glucagon (n = 13) and those without (n = 9) and compared for changes in MTT parameters. Then, they were also divided canagliflozin (Cana) group (n = 12) and other S (non-Cana) group (n = 10) and compared for changes in MTT parameters.

Results: Although those without increased AUC glucagon showed a significant increase in ΔCPR/Δglucose 0-30 min after improving glycemic control, those with increased AUC glucagon did not. Increased Δ CPR/Δ glucose 0-30 min values were noted in 5 of 13 of those with increased AUC glucagon but in 9/9 of those without, suggesting that those without increased AUC glucagon were more likely to be associated with increased Δ CPR/Δ glucose 0-30 min values. On the other hand, no significant difference was seen in changes in AUC glucagon or in the proportion of patients with increased AUC glucagon between the Cana and non-Cana groups.

Conclusions: Study results suggest that differences in the recovery of insulin secretion between patients may affect glucagon secretion to a greater extent than differences between S with or without SGLT1-inhibitory properties.


M. Ishiguro: None. Y. Mori: None. R. Nishimura: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly Japan K.K., Medtronic, Merck & Co., Inc., Novo Nordisk Inc., Sanofi K.K., Takeda Pharmaceutical Company Limited.

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