Canagliflozin: a sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes mellitus.

The sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin is a novel treatment option for adults with type 2 diabetes mellitus (T2DM). In patients with hyperglycemia, SGLT2 inhibition lowers plasma glucose levels by reducing the renal threshold for glucose (RTG ) and increasing urinary glucose excretion (UGE). Increased UGE is also associated with a mild osmotic diuresis and net caloric loss, which can lead to reductions in body weight and blood pressure (BP).

Diabetic Ketoacidosis and Related Events in the Canagliflozin Type 2 Diabetes Clinical Program.

Objective: This study assessed the incidence of serious adverse events of diabetic ketoacidosis (DKA) among patients with type 2 diabetes treated with canagliflozin.

Research Design And Methods: All serious adverse events of DKA and related events (ketoacidosis, metabolic acidosis, and acidosis) from 17,596 patients from randomized studies of canagliflozin through 11 May 2015 were analyzed.

Results: Serious adverse events of DKA and related events were reported in 12 patients (0.

Efficacy and safety of canagliflozin, an inhibitor of sodium-glucose cotransporter 2, when used in conjunction with insulin therapy in patients with type 2 diabetes.

Objective: There are limited data about the effects of sodium-glucose cotransporter 2 inhibitors when used with insulin. We report the efficacy and safety of canagliflozin in patients with type 2 diabetes using insulin.

Research Design And Methods: The CANagliflozin CardioVascular Assessment Study is a double-blind, placebo-controlled study that randomized participants to placebo, canagliflozin 100 mg, or canagliflozin 300 mg once daily, added to a range of therapies.

Successful integration of nonclinical and clinical findings in interpreting the clinical relevance of rodent neoplasia with a new chemical entity.

Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, has been developed for the treatment of adults with type 2 diabetes mellitus (T2DM). During the phase 3 program, treatment-related pheochromocytomas, renal tubular tumors, and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. Treatment-related tumors were not seen in the 2-year mouse study.

Carbohydrate malabsorption mechanism for tumor formation in rats treated with the SGLT2 inhibitor canagliflozin.

Canagliflozin is an SGLT2 inhibitor used for the treatment of type 2 diabetes mellitus. Studies were conducted to investigate the mechanism responsible for renal tubular tumors and pheochromocytomas observed at the high dose in a 2-year carcinogenicity study in rats. At the high dose (100mg/kg) in rats, canagliflozin caused carbohydrate malabsorption evidenced by inhibition of intestinal glucose uptake, decreased intestinal pH and increased urinary calcium excretion.

Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies.

Objective: To characterize genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) using pooled data from Phase 3 studies.

Research Design And Methods: Genital mycotic infections with canagliflozin 100 and 300 mg were evaluated in Population 1 (N = 2313; mean exposure [weeks]: canagliflozin, 24.3; placebo, 23.

Evaluation of vulvovaginal symptoms and Candida colonization in women with type 2 diabetes mellitus treated with canagliflozin, a sodium glucose co-transporter 2 inhibitor.

Background/objective: Women with type 2 diabetes mellitus (T2DM) are at increased risk for vaginal Candida colonization, perhaps because of glucosuria. Sodium glucose co-transporter 2 (SGLT2) inhibitors, in development for the treatment of T2DM, improve glycemic control by increasing urinary glucose excretion. Vaginal Candida colonization and symptomatic vulvovaginal adverse events (VVAE) were assessed in females with T2DM treated with canagliflozin, a SGLT2 inhibitor.

Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models.

Background: Canagliflozin is a sodium glucose co-transporter (SGLT) 2 inhibitor in clinical development for the treatment of type 2 diabetes mellitus (T2DM).

Methods: (14)C-alpha-methylglucoside uptake in Chinese hamster ovary-K cells expressing human, rat, or mouse SGLT2 or SGLT1; (3)H-2-deoxy-d-glucose uptake in L6 myoblasts; and 2-electrode voltage clamp recording of oocytes expressing human SGLT3 were analyzed. Graded glucose infusions were performed to determine rate of urinary glucose excretion (UGE) at different blood glucose (BG) concentrations and the renal threshold for glucose excretion (RT(G)) in vehicle or canagliflozin-treated Zucker diabetic fatty (ZDF) rats.

Optimized Basal-bolus insulin regimens in type 1 diabetes: insulin glulisine versus regular human insulin in combination with Basal insulin glargine.

Objective: To compare the efficacy and safety of insulin glulisine (GLU), a new rapid-acting insulin analogue, injected 0 to 15 minutes before or immediately after meals, with regular human insulin (RHI), injected 30 to 45 minutes before meals.

Methods: Patients with type 1 diabetes (N = 860) received once-daily insulin glargine and subcutaneous injections of either GLU (premeal or postmeal) or premeal RHI in this open-label, randomized, controlled, multicen-ter, parallel-group, 12-week study.

Results: Baseline to endpoint changes in mean gly-cated hemoglobin (as A1c equivalents) (A1c) occurred in the premeal GLU, postmeal GLU, and premeal RHI groups (-0.

Insulin glulisine provides improved glycemic control in patients with type 2 diabetes.

Objective: Insulin glulisine is a novel analog of human insulin designed for use as a rapid-acting insulin. This study compared the safety and efficacy of glulisine with regular human insulin (RHI) in combination with NPH insulin.

Research Design And Methods: In total, 876 relatively well-controlled patients with type 2 diabetes (mean HbA1c 7.

Activation of Erk1/Erk2 and transiently increased p53 levels together may account for p21 expression associated with phorbol ester-induced transient growth inhibition in HepG2 cells.

In HepG2 cells grown in the presence of serum, enhanced Raf-activation correlated with transient growth inhibition. The activation of Raf was increased either by the phorbol ester-induced activation of protein kinase C (PKC) or by the addition of the PKC inhibitor bisindolylmaleimide I (BIM). Either of these treatments increased the cellular levels of p21 by an Erk1/Erk2 MAP kinase cascade-dependent way, since this increase was prevented by the MEK-inhibitor PD98059.