An evaluation of canagliflozin for the treatment of type 2 diabetes: an update.

IntroductionSodium-glucose cotransporter-2 inhibitors (SGLT2is) are proven to ameliorate kidney and heart failure in patients with type 2 diabetes (T2D), in addition to improving glycemic controls. Canagliflozin is a SGLT2i and has proved beneficial for kidney and heart diseases in addition to decreasing the incidence of the composite outcomes of cardiovascular diseases and stroke.Areas coveredThis paper reviews the development of canagliflozin and its effects on renal dysfunction, heart failure, and vascular diseases.Expert opinionCanagliflozin contributes to the inhibition of renal function, decline progression and, therefore, is effective for T2D patients with chronic kidney dysfunction and albuminuria. The Canagliflozin Cardiovascular Assessment Study (CANVAS) revealed that patients showed increased incidence of amputation via unknown mechanisms, which has not been observed in other studies that used real-world data. Moreover, canagliflozin has been proven effective for anemia-associated outcomes of chronic kidney failure. Meta-analyses have revealed that canagliflozin contributed to lower diastolic blood pressure when compared with other SGLT2is. A subanalysis of CANVAS data proved that canagliflozin reduced the risk of hemorrhagic stroke. Canagliflozin should be used for T2D patients with chronic kidney failure and/or albuminuria and those with vascular diseases, with monitoring for ulcers and/or the pulse on the lower limb.

A case of an elderly patient with insulin-dependent diabetes and dementia receiving one basal insulin plus one bolus insulin injections a day for 6 months.

Multiple daily injections of insulin, referred to basal-bolus regimen, are generally essential in achieving glycemic control and preventing ketosis in insulin-dependent diabetes, such as type 1 diabetes (T1D). A 75-year-old man with T1D receiving basal-bolus insulin therapy exhibited symptoms of dementia after hospitalization due to pyelonephritis and failed to continue insulin self-injection. Given that his social and familial circumstances allowed insulin injection once a day during the morning, bolus insulin injections needed to be discontinued. Ketonuria was observed the day following discontinuation of bolus insulin. Although increasing the basal insulin dose (degludec) from 10 to 15 units improved ketonuria, his preprandial glucose levels increased to ≥ 500 mg/dL before lunch and ≥ 400 mg/dL before dinner. Hence, another bolus insulin injection was simultaneously added to the basal insulin dose before breakfast, which, subsequently, decreased his preprandial glucose levels to ≤ 220 mg/dL before lunch and ≤ 350 mg/dL before dinner. For half a year after discharge, ketonuria or hypoglycemia had not been detected. After 6 months, he was able to restart intensive insulin therapy with familial support. Hence, in cases where elderly patients with diabetes exhibit symptoms of dementia and can receive insulin injection once a day due to their social circumstances, short-term one basal plus one bolus insulin injections a day might be considered to prevent life-threatening diabetes complications among those who are insulin-dependent.

Effects of Canagliflozin on Hepatic Steatosis, Visceral Fat and Skeletal Muscle among Patients with Type 2 Diabetes and Non-alcoholic Fatty Liver Disease.

Objective We assessed the effect of canagliflozin, an sodium-glucose co-transporter type-2 inhibitor, on hepatic steatosis using three imaging modalities: magnetic resonance imaging (MRI), computed tomography, and transient elastography. We further determined factors associated with improving hepatic steatosis by canagliflozin among patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Methods We conducted a six-month prospective single-arm study between August 2015 and June 2017. The primary outcome was the change in hepatic steatosis assessed using the hepatic proton density fat fraction (PDFF) on MRI before and after treatment with canagliflozin. The secondary outcomes were changes in measures of glucose metabolism, including the hepatic glucose uptake on fluorodeoxyglucose-positron emission tomography, and the inflammation and volumes of visceral and subcutaneous adipose tissue and skeletal muscle. Patients Nine patients with type 2 diabetes and NAFLD completed this study. All participants received canagliflozin at a dose of 100 mg daily. Results Canagliflozin caused a significant reduction in hepatic PDFF from baseline [median 20.6% (interquartile range 11.7%, 29.8%)] after 6 months [10.6% (5.4%, 22.6%), p=0.008]. Canagliflozin also significantly reduced the body weight, glycated hemoglobin, homeostasis model assessment of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hs-CRP), and volumes of adipose tissue and skeletal muscle (all p<0.05). The reduction in hepatic PDFF was not correlated with changes in the body weight, HOMA-IR, hs-CRP, or volume of adipose tissue and skeletal muscle from baseline after six months. Conclusion Among patients with type 2 diabetes and NAFLD, canagliflozin improved hepatic steatosis. The effect may be independent of reducing adiposity, insulin resistance, inflammation, and skeletal muscle volume.

The effect of long-term past glycemic control on executive function among patients with type 2 diabetes mellitus.

OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) show more executive dysfunction than nondiabetics. However, how long poor glycemic control affects executive function remains unclear. Thus, we aimed to investigate the relationships in a cross-sectional study. METHODS: We studied 118 T2DM outpatients (age, ≥ 60 years; excluding history of stroke, dementia and severe hypoglycemia). HbA1c values were recorded every ≤ 12 weeks for ≥ 5 years. All patients underwent verbal-fluency tests (reflecting executive function) and Mini-Mental State Examination (MMSE). The correlation between past glycemic control values and both cognitive tests scores was investigated. As markers of past glycemic control, we used average hemoglobin A1c (HbA1c) values and glycemic control variability [coefficient of variation (CV) of HbA1c values (HbA1c-CV)]. RESULTS: Verbal-fluency tests scores correlated with HbA1c-CV, but not with average HbA1c values, after adjusting for age, years of education and sex. Verbal-fluency tests scores correlated with HbA1c-CV for the past 5 years, best compared with HbA1c-CV for past < 5 years. MMSE scores were also related to only HbA1c-CV for the past 3 years in an adjustment model. CONCLUSIONS: Five-year HbA1c variability affected executive function in T2DM patients, but not average HbA1c values. Long-term longitudinal studies may be required.

Effects of switching to low-dose rosuvastatin (5 mg/day) on glucose metabolism and lipid profiles in Japanese patients with type 2 diabetes and dyslipidemia: a single-arm, prospective, interventional trial.

AIMS: We investigated the effects of switching from other statins, such as pravastatin (5 or 10 mg/day), rosuvastatin (2.5 mg/day), or pitavastatin (1 or 2 mg/day), to low-dose rosuvastatin (5 mg/day) on glucose metabolism and lipid profiles in Japanese patients with type 2 diabetes and dyslipidemia. METHODS: This was a prospective, two-center, open-label, single-arm, interventional trial. Several clinical parameters were analyzed at baseline and 24 weeks after switching from other statins to rosuvastatin at 5 mg/day. The primary endpoints were changes in hemoglobin (Hb) A1c level and lipid profile. RESULTS: Forty-five patients were enrolled in the trial. The mean HbA1c level increased significantly from 7.1 ± 0.7 to 7.5 ± 0.9% (P < 0.001), whereas the mean low-density lipoprotein cholesterol (LDL-C) level decreased significantly from 108.9 ± 16.5 to 91.6 ± 24.5 mg/dL (P < 0.001). Multiple linear regression analysis showed that changes in HbA1c levels were significantly and positively correlated with fasting plasma glucose (FPG) levels at baseline. Receiver operating characteristic (ROC) curve analysis examining the relationship between HbA1c and FPG showed that FPG was a significant predictor of changes in HbA1c levels (area under the curve, 0.72). The cutoff FPG value of 168 mg/dL had a sensitivity of 47% and a specificity of 93%. CONCLUSIONS: Switching to a low dose of rosuvastatin impaired glucose metabolism in Japanese patients with type 2 diabetes and dyslipidemia. Patients with high FPG levels were particularly prone to an exacerbation of glucose metabolism.