Effect of canagliflozin on the overall clinical state including insulin resistance in Japanese patients with type 2 diabetes mellitus.

AIMS: Information on the clinical efficacy of SGLT2 inhibitors in the Japanese population is limited. The aim of this single-arm, single-center, open-label study was to confirm the body weight- and fat mass-lowering effects of canagliflozin (CANA) and the accompanying improvement in insulin resistance in Japanese patients with Type 2 diabetes mellitus (T2DM). METHODS: Thirty-eight patients were enrolled and administered 100 mg CANA once daily for 24 weeks. Blood and anthropometric parameters were examined before and after treatment. In a subset of patients, insulin sensitivity was assessed based on the glucose infusion rate (GIR) during a hyperinsulinemic euglycemic clamp test. RESULTS: CANA treatment significantly decreased hemoglobin A1c, fasting plasma glucose, and plasma liver enzyme levels, and increased plasma adiponectin levels. In addition, a significant reduction in body weight, visceral and subcutaneous fat area, fat and lean mass, and liver steatosis was also observed. The change in plasma adiponectin levels significantly correlated with the changes in both body fat mass and visceral fat area. GIR increased from 3.25 ±â€¯1.53 to 4.11 ±â€¯1.30 mg/kg/min (P < 0.05). CONCLUSIONS: CANA improved insulin resistance and decreased visceral fat mass in Japanese patients with T2DM.

Both glimepiride and high-dose metformin are important for sustained glucose lowering in Japanese type 2 diabetes patients on glimepiride-sitagliptin-metformin therapy: subanalysis of a single-center, open-label, randomized study.

BACKGROUND: In a previous single-center, open-label randomized 3-month study of triple oral antidiabetes drug (OAD) therapy, we investigated factors affecting the glycemic control afforded by sitagliptin, high-dose metformin, and low-dose glimepiride. Patients were prospectively assigned to either Group 1 (50% reduction in metformin) or Group 2 (discontinuation of glimepiride) and compared. The results showed that the glycated hemoglobin (HbA1c) levels of patients in Group 2 deteriorated more than those in Group 1, whereas HbA1c levels were maintained in some patients in both groups. MATERIALS AND METHODS: To determine the factors associated with maintenance of HbA1c under this triple OAD regimen, data from the prospective study were further analyzed. RESULTS: In both Groups 1 and 2, the baseline HbA1c level was higher in patients with HbA1c ≥7.0% after 3 months of treatment than those with an HbA1c level of <7.0%. A generalized linear model revealed that high-dose metformin was associated with a deterioration of HbA1c levels in Group 2. CONCLUSIONS: Together, the findings indicate that glimepiride and high-dose metformin are important for sustained glycemic control in triple OAD therapy with sitagliptin, metformin, and sulfonylurea.

Effects of celiac superior mesenteric ganglionectomy on glucose homeostasis and hormonal changes during oral glucose tolerance testing in rats.

The liver plays an important role in maintaining glucose homeostasis in the body. In the prandial state, some of the glucose which is absorbed by the gastrointestinal tract is converted into glycogen and stored in the liver. In contrast, the liver produces glucose by glycogenolysis and gluconeogenesis while fasting. Thus, the liver contributes to maintaining blood glucose level within normoglycemic range. Glycogenesis and glycogenolysis are regulated by various mechanisms including hormones, the sympathetic and parasympathetic nervous systems and the hepatic glucose content. In this study, we examined a rat model in which the celiac superior mesenteric ganglion (CSMG) was resected. We attempted to elucidate how the celiac sympathetic nervous system is involved in regulating glucose homeostasis by assessing the effects of CSMG resection on glucose excursion during an oral glucose tolerance test, and by examining hepatic glycogen content and hepatic glycogen phosphorylase (GP) activity. On the oral glucose tolerance test, CSMG-resected rats demonstrated improved glucose tolerance and significantly increased GP activity compared with sham-operated rats, whereas there were no significant differences in insulin, glucagon or catecholamine levels between the 2 groups. These results suggest that the celiac sympathetic nervous system is involved in regulating the rate of glycogen consumption through GP activity. In conclusion, the examined rat model showed that the celiac sympathetic nervous system regulates hepatic glucose metabolism in conjunction with vagal nerve innervations and is a critical component in the maintenance of blood glucose homeostasis.