The sodium–glucose cotransporter 2 inhibitor ipragliflozin improves liver function and insulin resistance in Japanese patients with type 2 diabetes

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.

Metabolomic analysis of serum samples from a clinical study on ipragliflozin and metformin treatment in Japanese patients with type 2 diabetes: Exploring human metabolites associated with visceral fat reduction

“…However, the decrease in these levels observed in the metformin group may have been caused by vitamin B12 deficiency because of metformin. Finally, a previous study reported that SGLT2 inhibitors improved liver function, decreased hepatic insulin resistance, and increased hepatic insulin clearance 50 …”

“…Finally, a previous study reported that SGLT2 inhibitors improved liver function, decreased hepatic insulin resistance, and increased hepatic insulin clearance. 50 This is the first study that identified metabolites in serum sam- This study has several limitations. First, unfortunately, we…”

Urinary α1 microglobulin level is useful for selecting sodium‐glucose transporter 2 inhibitor or metformin for visceral fat reduction in patients with type 2 diabetes

“…Ipragliflozin treatment has been reported to improve liver function. 16 In the metformin group, responders had high HbA1c levels at baseline and the high fasting blood glucose levels decreased after 24 weeks. Therefore, metformin is more suitable for patients with worse blood glucose control.…”

“…GPT levels decreased in the ipragliflozin group, which may reflect the amelioration of fatty liver disease. Ipragliflozin treatment has been reported to improve liver function 16 . In the metformin group, responders had high HbA1c levels at baseline and the high fasting blood glucose levels decreased after 24 weeks.…”

Fasting hepatic insulin clearance reflects postprandial hepatic insulin clearance: a brief report

“…Despite these limitations, we consider that our study would contribute to our daily clinical work or clinical studies. We previously reported that SGLT2 inhibitor increased postprandial HIC, and decreased hyperinsulinemia, insulin resistance, and liver functions [ 28 ]. We consider that our findings contribute to the treatment strategy, because we can estimate postprandial HIC from only one fasting blood sample based on our results.…”