sitagliptin-phosphate and Urinary-Tract-Infections

To evaluate the efficacy and safety of titrated canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin and sitagliptin.. In this randomized, double-blind study, patients with T2DM (N = 218) on metformin ≥1500 mg/day and sitagliptin 100 mg received canagliflozin 100 mg or placebo. After 6 weeks, the canagliflozin dose was increased from 100 to 300 mg (or from placebo to matching placebo) if all of the following criteria were met: baseline estimated glomerular filtration rate ≥70 ml/min/1.73 m(2) ; fasting self-monitored blood glucose ≥5.6 mmol/l (≥100 mg/dl); and no volume depletion-related adverse events (AEs) within 2 weeks before dose increase. Endpoints included change in glycated haemoglobin (HbA1c) at week 26 (primary); proportion of patients achieving HbA1c <7.0%; and changes in fasting plasma glucose (FPG), body weight and systolic blood pressure (SBP). Safety was assessed using AE reports.. Overall, 85.4% of patients were titrated to canagliflozin 300 mg or matching placebo (mean ± standard deviation time to titration 6.2 ± 0.8 weeks). At week 26, canagliflozin (pooled 100 and 300 mg) demonstrated superiority in HbA1c reduction versus placebo (-0.91% vs. -0.01%; p < 0.001). Canagliflozin provided significant reductions in FPG, body weight and SBP compared with placebo (p < 0.001). The overall AE incidence was 39.8 and 44.4% for canagliflozin and placebo, respectively. Canagliflozin was associated with an increased incidence of genital mycotic infections.. Titrated canagliflozin significantly improved HbA1c, FPG, body weight and SBP, and was generally well tolerated over 26 weeks in patients with T2DM as add-on to metformin and sitagliptin.

Topics: Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Hypovolemia; Male; Metformin; Middle Aged; Mycoses; Reproductive Tract Infections; Sitagliptin Phosphate; Treatment Failure; Treatment Outcome; Urinary Tract Infections

To investigate the efficacy and safety of ertugliflozin, in a phase II dose-ranging study, in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin.. A total of 328 patients [mean T2DM duration, 6.3 years; mean glycated haemoglobin (HbA1c), 8.1%] were randomized to once-daily ertugliflozin (1, 5, 10, 25 mg), sitagliptin (100 mg) or placebo, for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in HbA1c concentration and the secondary efficacy endpoints were changes from baseline to week 12 in body weight, fasting plasma glucose (FPG) and systolic/diastolic blood pressure (SBP/DBP). Safety and tolerability were also monitored.. Ertugliflozin (1-25 mg/day) produced significant reductions in HbA1c concentration [placebo-corrected least-squares mean (LSM) -0.45% (1 mg) to -0.72% (25 mg); p ≤ 0.002, similar to sitagliptin (-0.76%; p = 0.0001)], FPG (LSM -1.17 to -1.90 mmol/l; p < 0.0001) and body weight (-1.15 to -2.15%; p < 0.0001). The LSM SBP decreased by -3.4 to -4.0 mmHg from baseline with ertugliflozin 5-25 mg/day. No reductions in body weight or blood pressure were observed with sitagliptin. After randomization, 2.7% of patients (9/328) withdrew because of adverse events (AEs); the frequency of AEs was evenly distributed across groups. No dose-related increase in AE frequency occurred with ertugliflozin. Hypoglycaemia was reported in 5 (1.5%) randomized participants (all in the ertugliflozin group). The frequency of urinary tract infection was 3.2% for ertugliflozin (pooled across groups), 1.8% for sitagliptin, 7.4% for placebo, and the frequency of genital fungal infections was 3.7% for ertugliflozin (pooled) versus 1.9% for placebo.. Ertugliflozin (1-25 mg/day) improved glycaemic control, body weight and blood pressure in patients with T2DM suboptimally controlled on metformin, and was well tolerated.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Bridged Bicyclo Compounds, Heterocyclic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Genital Diseases, Female; Genital Diseases, Male; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Mycoses; Sitagliptin Phosphate; Sodium-Glucose Transport Proteins; Urinary Tract Infections

To assess the efficacy and safety of dapagliflozin as add-on therapy in patients with type 2 diabetes who were inadequately controlled with a dipeptidyl peptidase-4 inhibitor with or without metformin.. In this 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 study with a 24-week blinded extension period, 432 patients were randomized to receive dapagliflozin 10 mg/day or placebo added to sitagliptin (100 mg/day) ± metformin (≥1,500 mg/day).. Baseline HbA1c and FPG levels were 7.9% (63.0 mmol/mol) and 162.2 mg/dL (9.0 mmol/L) for the dapagliflozin group and 8.0% (64.0 mmol/mol) and 163 mg/dL (9.0 mmol/L) for placebo. At week 24, dapagliflozin significantly reduced mean HbA1c levels (-0.5% [-4.9 mmol/mol]) versus placebo (0.0% [+0.4 mmol/mol]). Dapagliflozin reduced body weight versus placebo (-2.1 and -0.3 kg) and reduced HbA1c levels in patients with baseline values ≥8.0% (-0.8% [8.7 mmol/mol] and 0.0% [0.3 mmol/mol]) and fasting plasma glucose levels (-24.1 mg/dL [-1.3 mmol/L] and 3.8 mg/dL [0.2 mmol/L]). Similar results were observed when data were stratified by background therapy. Glycemic and weight benefits observed at week 24 were maintained through week 48. Changes from baseline in systolic blood pressure at week 8 were not significantly different between treatment groups. Over 48 weeks, fewer patients receiving dapagliflozin were discontinued or rescued for failing to achieve glycemic targets compared with placebo. Adverse events were balanced between groups, and discontinuation rates were low. At week 48, signs and symptoms suggestive of genital infection were more frequent with dapagliflozin (9.8%) than with placebo (0.4%). Signs and symptoms suggestive of urinary tract infection were balanced between dapagliflozin (6.7%) and placebo (6.2%).. These results suggest that in patients with type 2 diabetes, inadequately controlled on sitagliptin with or without metformin, add-on treatment with dapagliflozin provides additional clinical benefit and is well tolerated.

Topics: Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Urinary Tract Infections; Weight Loss

To examine the effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor that lowers blood glucose by increasing urinary glucose excretion (UGE), on asymptomatic bacteriuria and urinary tract infections (UTIs).. In a randomized, double-blind, placebo-controlled, multicenter, dose-ranging phase 2 study, subjects with type 2 diabetes with inadequate glycemic control while receiving metformin were enrolled and randomized to one of seven arms - placebo; canagliflozin doses 50 mg, 100 mg, 200 mg, 300 mg daily, or 300 mg twice daily; and sitagliptin 100 mg daily - for 12 weeks.. This study is registered under Clinicaltrials.gov identification number NCT00642278.. Canagliflozin increased renal glucose excretion by 35.4-61.6 mg/mg creatinine in the five dose groups. In the placebo group renal glucose excretion was increased by 1.9 mg/mg creatinine, and in the sitagliptin group it decreased by 1.9 mg/mg creatinine. Asymptomatic bacteriuria (ASB) were present in 6.4% of canagliflozin and 6.5% of placebo/sitagliptin (control) subjects at randomization and, at 12 weeks, in 7.7% and 6.3% of subjects, respectively (odds ratio [OR] 1.23; 95% confidence interval [CI], 0.45-3.89). For subjects with initially negative urine cultures at baseline, 3 out of 82 (3.7%) who received controls and 10 out of 207 (4.8%) who received canagliflozin developed bacteriuria (p = 0.76) at week 12. There were 21 adverse event (AE) reports of UTI; 16 (5.0%) in canagliflozin subjects and 5 (3.8%) in control subjects (OR 1.31; 95% CI, 0.45-4.68).. In this trial, when compared with control subjects, canagliflozin increased UGE but was not associated with increased bacteriuria or AE reports of UTI. However, further studies enrolling larger numbers of subjects with longer term exposure to canagliflozin will be necessary to more fully understand the impact of this agent on the risk of developing UTI.

Topics: Bacteriuria; Blood Glucose; Canagliflozin; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucosides; Glycosuria; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Pyrazines; Sitagliptin Phosphate; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes; Triazoles; Urinary Tract Infections