Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy (VERTIS MET)

• Published in: Diabetes, obesity & metabolism Vol. 20; no. 3; pp. 520 - 529
• Main Authors: Rosenstock, Julio, Frias, Juan, Páll, Dénes, Charbonnel, Bernard, Pascu, Raluca, Saur, Didier, Darekar, Amanda, Huyck, Susan, Shi, Harry, Lauring, Brett, Terra, Steven G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2018; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Antidiabetics; Blood Glucose - drug effects; Blood Glucose - metabolism; Blood pressure; Blood Pressure - drug effects; Body weight; Bone density; Bone Density - drug effects; Bone mineral density; Bridged Bicyclo Compounds, Heterocyclic - administration & dosage; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - physiopathology; Diabetes Mellitus, Type 2 - prevention & control; Double-Blind Method; ertugliflozin; Female; Glycated Hemoglobin A - metabolism; Humans; Hypoglycemia; Hypoglycemic Agents - administration & dosage; Infections; Male; Metformin; Metformin - administration & dosage; Middle Aged; SGLT2 inhibitor; Sodium-Glucose Transporter 2 Inhibitors - administration & dosage; Treatment Outcome; type 2 diabetes mellitus; Urinary tract; Weight Loss - drug effects; Young Adult; type 2 diabetes mellitus; bone mineral density; ertugliflozin; SGLT2 inhibitor
• ISSN: 1462-8902; 1463-1326; 1463-1326
• DOI: 10.1111/dom.13103

Aim We evaluated the efficacy and safety of ertugliflozin, an SGLT2 inhibitor, in type 2 diabetes mellitus (T2DM) inadequately controlled (HbA1c, 7.0%‐10.5%) with metformin monotherapy (≥1500 mg/d for ≥8 weeks). Methods This was a double‐blind, 26‐week, multicentre study with ongoing 78‐week extension (ClinicalTrials.gov identifier: NCT02033889). A total of 621 participants were randomized 1:1:1 to placebo, or ertugliflozin 5 or 15 mg/d. The primary endpoint was change from baseline at week 26 in HbA1c. Secondary efficacy endpoints were change from baseline at week 26 in fasting plasma glucose (FPG), body weight, systolic/diastolic blood pressure (SBP/DBP) and number of participants with HbA1c <7.0% (53 mmol/mol). Pre‐specified adverse events (AEs) of special interest and percent change from baseline in bone mineral density (BMD) were also assessed at week 26. Results At week 26, the placebo‐adjusted least‐squares mean change from baseline HbA1c (8.1%) was −0.7% and −0.9% for ertugliflozin 5 and 15 mg, respectively (both P < .001), to final means of 7.3% and 7.2%, respectively. The odds of HbA1c <7.0% were significantly greater in both ertugliflozin groups vs placebo. Ertugliflozin significantly reduced FPG, body weight, SBP and DBP vs placebo. The incidence of genital mycotic infections was higher in the ertugliflozin groups (female subjects: placebo, 0.9%; ertugliflozin 5 mg, 5.5%; ertugliflozin 15 mg, 6.3% [P = .032]; male subjects: 0%; 3.1%; 3.2%, respectively), as was the incidence of urinary tract infections and symptomatic hypoglycaemia. The incidence of hypovolaemia AEs was similar across groups. Ertugliflozin had no adverse impact on BMD at week 26. Conclusions Ertugliflozin added to metformin in patients with inadequately controlled T2DM improved glycaemic control, reduced body weight and BP, but increased the incidence of genital mycotic infections.