pf-04971729 and Mycoses

To evaluate the effectiveness and safety of the novel sodium-glucose cotransporter inhibitor, ertugliflozin, compared with a placebo or other antihyperglycemic agents for type 2 diabetes patients.. We carried out a meta-analysis of randomized controlled trials to assess the benefits and harms of ertugliflozin. Online database searches were carried out in PubMed, EMBASE, WEB OF SCIENCE and Cochrane from inception up to 11 March 2021. Our end-points were glycated hemoglobin, fasting plasma glucose and bodyweight. We analyzed the results using a random effects model, computed weighted mean differences and risk ratios.. A total of 10 randomized controlled trials with 13,223 patients met the inclusion criteria. Compared with a placebo, the weighted mean differences in glycated hemoglobin were -0.77% (95% confidence interval [CI] -0.86 to -0.68%) for ertugliflozin 5 mg, and -0.82% (95% CI -1.01 to -0.63%) for ertugliflozin 15 mg. Ertugliflozin 5 mg daily was also associated with bodyweight loss (weighted mean difference -1.87 kg, 95% CI -2.12 to -1.6). When compared with a placebo, ertugliflozin significantly reduced fasting plasma glucose by -1.62 mmol/L (weighted mean difference, 95% CI -1.82 to -1.42 for 5 mg ertugliflozin). Yet, we observed a rising risk for genital mycotic infections (risk ratio 4.34, 95% CI 2.78-6.76). The results were similar for the 15 mg ertugliflozin group.. Ertugliflozin effectively reduces glycated hemoglobin levels and provides extra clinical benefits including bodyweight and fasting plasma glucose. Common adverse effects, including genital mycotic infections and so on, were reviewed.

Topics: Blood Glucose; Bridged Bicyclo Compounds, Heterocyclic; Diabetes Mellitus, Type 2; Genital Diseases; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Mycoses; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors

Topics: Adult; Aged; Black People; Bridged Bicyclo Compounds, Heterocyclic; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Male; Middle Aged; Mycoses; Sodium-Glucose Transporter 2 Inhibitors; White People

To evaluate the long-term efficacy and safety of ertugliflozin in adults with type 2 diabetes mellitus inadequately controlled on metformin.. A 104-week Phase III, randomized double-blind study with a 26-week placebo-controlled period (Phase A) and a 78-week period (Phase B) where blinded glimepiride was added to non-rescued placebo participants with fasting fingerstick glucose ≥6.1 mmol/L. Results through week 104 are reported.. Mean (standard error) change in HbA1c from baseline was -0.7% (0.07) and -1.0% (0.07) at week 52; -0.6% (0.08) and -0.9% (0.08) at week 104 for ertugliflozin 5 and 15 mg. At week 52, 34.8% and 36.6% participants had HbA1c <7.0%, and 24.6% and 33.7% at week 104, for ertugliflozin 5 and 15 mg. Ertugliflozin reduced fasting plasma glucose (FPG), body weight and systolic blood pressure (SBP) from baseline through week 104. The incidence of female genital mycotic infections (GMIs) was higher with ertugliflozin, and symptomatic hypoglycaemia was lower for ertugliflozin versus placebo/glimepiride. Minimal bone mineral density (BMD) changes were observed, similar to placebo/glimepiride, except at total hip where reduction in BMD was greater with ertugliflozin 15 mg versus placebo/glimepiride: difference in least squares means (95% CI) -0.50% (-0.95, -0.04) at week 52 and -0.84% (-1.44, -0.24) at week 104.. Ertugliflozin maintained improvements from baseline in HbA1c, FPG, body weight and SBP through week 104. Ertugliflozin was well tolerated, with non-clinically relevant changes in BMD. Compared with placebo/glimepiride, ertugliflozin increased female GMIs, but reduced the incidence of symptomatic hypoglycaemia. ClinicalTrials.gov Identifier: NCT02033889.

Topics: Aged; Blood Glucose; Bone Density; Bridged Bicyclo Compounds, Heterocyclic; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Mycoses; Reproductive Tract Infections; Sulfonylurea Compounds; Vulvovaginitis

To conduct a phase III study to evaluate the efficacy and safety of ertugliflozin monotherapy in people with type 2 diabetes.. This was a 52-week, double-blind, multicentre, randomized, parallel-group study with a 26-week, placebo-controlled treatment period (phase A), followed by a 26-week active-controlled treatment period (phase B) in 461 men and women, aged ≥18 years with inadequate glycaemic control (glycated haemoglobin [HbA1c] concentration 7.0% to 10.5% [53-91 mmol/mol], inclusive) despite diet and exercise. Results from phase A are reported in the present paper. The primary endpoint was the change in HbA1c from baseline to week 26.. At week 26, the placebo-adjusted least squares mean HbA1c changes from baseline were -0.99% and -1.16% for the ertugliflozin 5 and 15 mg doses, respectively ( P  < .001 for both doses). The odds of having HbA1c <7.0% (53 mmol/mol) were significantly greater in the ertugliflozin 5 and 15 mg groups compared with the placebo group. Both doses of ertugliflozin significantly lowered fasting plasma glucose and 2-hour postprandial glucose levels and body weight. The placebo-adjusted differences in changes from baseline in systolic blood pressure were not statistically significant. A higher incidence of genital mycotic infections occurred in men and women treated with ertugliflozin compared with placebo. There was no significant difference between treatments in the proportion of participants with symptomatic hypoglycaemia or adverse events associated with urinary tract infection or hypovolaemia.. Ertugliflozin 5 and 15 mg treatment for 26 weeks provides effective glycaemic control, reduces body weight and is generally well tolerated, when used as monotherapy.

Topics: Anti-Obesity Agents; Bridged Bicyclo Compounds, Heterocyclic; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diet, Diabetic; Dose-Response Relationship, Drug; Double-Blind Method; Exercise; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Immunity, Mucosal; Incidence; Male; Membrane Transport Modulators; Mycoses; Overweight; Reproductive Tract Infections; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors

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