Abstract
Sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment is a therapeutic approach for type 2 diabetes mellitus (T2DM). Some reports have shown that SGLT2i treatment improves insulin resistance; however, few studies have evaluated insulin resistance by the glucose clamp method. Hepatic insulin clearance (HIC) is a new pathophysiological mechanism of T2DM. The effect of SGLT2i treatment on hepatic insulin clearance and insulin resistance is not well known. We investigated the effect of SGLT2i treatment on insulin resistance, insulin secretion, incretin levels, body composition, and hepatic insulin clearance. We conducted a meal tolerance test (MTT) and a hyperinsulinemic-euglycemic clamp test in 9 T2DM patients. Ipragliflozin (50 mg/day) was administered, and the MTT and clamp test were performed after 4 months. We calculated HIC as the postprandial C-peptide AUC-to-insulin AUC ratio. We also measured GLP-1, GIP, and glucagon levels during the MTT. Body weight and HbA1c were decreased, although not significantly, after 4 months of treatment. Postprandial glucose, fasting insulin and postprandial insulin were significantly decreased. Insulin resistance with the glucose clamp was not changed, but the HOMA-IR and insulin sensitivity indices were significantly improved. Incretin and glucagon levels were not changed. Hepatic insulin clearance was significantly increased, but whole-body insulin clearance was not changed. The FIB-4 index and fatty liver index were significantly reduced. The HOMA-beta and insulinogenic indices were not changed, but the C-peptide index was significantly increased. Although the number of patients was small, these results suggested that SGLT2i treatment improved liver function, decreased hepatic insulin resistance, and increased hepatic insulin clearance, despite the small weight reduction.
Highlights
Abbreviations ALT Alanine aminotransferase AST Aspartate aminotransferase AUC Area under the curve BMI Body mass index CPI C-peptide index CPR C-peptide immunoreactivity eGFR Estimated glomerular filtration rate FLI Fatty liver index glucose disposal rate (GDR) Glucose disposal rate
A glucose clamp test and an oral glucose tolerance test were performed, and Sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment was found to improve insulin sensitivity in an American p opulation[5]. These results suggest that SGLT2i treatment improves muscle insulin sensitivity but increases endogenous glucose production via glucagon secretion
We evaluated the effect of SGLT2i treatment on insulin resistance and whole-body insulin clearance by the glucose clamp method, and we evaluated the effect on hepatic insulin clearance and beta-cell function by a meal tolerance test in Japanese individuals
Summary
Abbreviations ALT Alanine aminotransferase AST Aspartate aminotransferase AUC Area under the curve BMI Body mass index CPI C-peptide index CPR C-peptide immunoreactivity eGFR Estimated glomerular filtration rate FLI Fatty liver index GDR Glucose disposal rate. In one study performed by dual-tracer glucose administration combined with a mixed meal in a European population, SGLT2i treatment increased insulin sensitivity and the secretion of glucagon-like peptide-1 (GLP-1) but increased endogenous glucose production and glucagon s ecretion[4]. A glucose clamp test and an oral glucose tolerance test were performed, and SGLT2i treatment was found to improve insulin sensitivity in an American p opulation[5]. These results suggest that SGLT2i treatment improves muscle insulin sensitivity but increases endogenous glucose production via glucagon secretion. An American study showed that the SGLT2i canagliflozin improved liver insulin sensitivity and beta-cell function and increased hepatic insulin clearance, as evaluated by the glucose clamp method and a mixed meal tolerance test[9]. We need an study of SGLT2i treatment in Asian individuals
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
