Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes on a background of metformin

• Published in: Diabetes, obesity & metabolism Vol. 17; no. 6; pp. 591 - 598
• Main Authors: Amin, N. B., Wang, X., Jain, S. M., Lee, D. S., Nucci, G., Rusnak, J. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2015; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Antidiabetics; Blood Glucose - drug effects; Blood Glucose - metabolism; Blood pressure; Blood Pressure - drug effects; Body weight; Body Weight - drug effects; Bridged Bicyclo Compounds, Heterocyclic - administration & dosage; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination - methods; ertugliflozin; Female; Genital Diseases, Female - chemically induced; Genital Diseases, Male - chemically induced; Glucose; Glucose transporter; Glycated Hemoglobin A - drug effects; Glycated Hemoglobin A - metabolism; HbA1c; Hemoglobin; Humans; Hypoglycemia; Hypoglycemia - chemically induced; Hypoglycemic Agents - administration & dosage; Male; Metformin; Metformin - administration & dosage; Middle Aged; Mycoses - chemically induced; PF-04971729; Safety; Sitagliptin Phosphate - administration & dosage; Sodium; sodium-glucose linked co-transporter (SGLT); Sodium-Glucose Transport Proteins - antagonists & inhibitors; type 2 diabetes mellitus (T2DM); Urinary tract; Urinary Tract Infections - chemically induced; sodium-glucose linked co-transporter (SGLT); PF-04971729; ertugliflozin; HbA1c; type 2 diabetes mellitus (T2DM)
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12460

Aim 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. Methods 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. Results 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. Conclusion 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.