Ertugliflozin plus sitagliptin versus either individual agent over 52 weeks in patients with type 2 diabetes mellitus inadequately controlled with metformin: The VERTIS FACTORIAL randomized trial

Abstract

AimTo evaluate the efficacy and safety of ertugliflozin and sitagliptin co‐administration vs the individual agents in patients with type 2 diabetes who are inadequately controlled with metformin.MethodsIn this study (http://Clinicaltrials.gov NCT02099110), patients with glycated haemoglobin (HbA1c) ≥7.5% and ≤11.0% (≥58 and ≤97 mmol/mol) with metformin ≥1500 mg/d (n = 1233) were randomized to ertugliflozin 5 (E5) or 15 (E15) mg/d, sitagliptin 100 mg/d (S100) or to co‐administration of E5/S100 or E15/S100. The primary endpoint was change from baseline in HbA1c at Week 26.ResultsAt Week 26, least squares mean HbA1c reductions from baseline were greater with E5/S100 (−1.5%) and E15/S100 (−1.5%) than with individual agents (−1.0%, −1.1% and −1.1% for E5, E15 and S100, respectively; P < .001 for all comparisons). HbA1c <7.0% (<53 mmol/mol) was achieved by 26.4%, 31.9%, 32.8%, 52.3% and 49.2% of patients in the E5, E15, S100, E5/S100 and E15/S100 groups, respectively. Fasting plasma glucose reductions were significantly greater with E5/S100 and E15/S100 compared with individual agents. Body weight and systolic blood pressure (SBP) significantly decreased with E5/S100 and E15/S100 vs S100 alone. Glycaemic control, body weight and SBP effects of ertugliflozin were maintained to Week 52. Genital mycotic infections were more common among ertugliflozin‐treated patients compared with those treated with S100. Incidences of symptomatic hypoglycaemia and adverse events related to hypovolaemia or urinary tract infection were similar among groups.ConclusionsIn patients with uncontrolled type 2 diabetes while using metformin, co‐administration of ertugliflozin and sitagliptin provided more effective glycaemic control through 52 weeks compared with the individual agents.

Assessment of the Drug Interaction Potential of Ertugliflozin With Sitagliptin, Metformin, Glimepiride, or Simvastatin in Healthy Subjects

“…5,7 It is likely to be used in combination with a number of other antihyperglycemic and lipid-lowering agents (eg, statins) for comorbidities associated with diabetes. 5,7 It is likely to be used in combination with a number of other antihyperglycemic and lipid-lowering agents (eg, statins) for comorbidities associated with diabetes.…”

“…5,7 It is likely to be used in combination with a number of other antihyperglycemic and lipid-lowering agents (eg, statins) for comorbidities associated with diabetes. 5 Similar to these results, on a background of metformin, ertugliflozin at 5-and 15-mg doses provided sustained glycemic control over 52 weeks. 5,7,22,23 Coadministration of ertugliflozin with sitagliptin 100 mg provided greater glycemic control compared with each individual dose of ertugliflozin and sitagliptin with inadequate control on either metformin or diet and exercise.…”

“…5,7,22,23 Coadministration of ertugliflozin with sitagliptin 100 mg provided greater glycemic control compared with each individual dose of ertugliflozin and sitagliptin with inadequate control on either metformin or diet and exercise. 5,7,22 Due to the linear and time-independent PK of ertugliflozin, single-dose PK are predictive of multiple-dose PK of ertugliflozin. 23 Ertugliflozin as an add-on to metformin, and metformin and sitagliptin, also provided clinically meaningful body weight and systolic blood pressure reductions.…”

A Phase 1, Randomized, Placebo‐ and Active‐Controlled Crossover Study to Determine the Effect of Single‐Dose Ertugliflozin on QTc Interval in Healthy Volunteers

“…Results of phase 3 studies of ertugliflozin in patients with T2DM inadequately controlled with diet and exercise alone demonstrate that, when used either as monotherapy or in combination with sitagliptin, at doses of 5 mg and 15 mg for 26 weeks, ertugliflozin provided effective glycemic control, reduced body weight, and was generally well tolerated. Other phase 3 studies have shown that administration of ertugliflozin at doses of 5 mg or 15 mg to patients with T2DM inadequately controlled on metformin or metformin and sitagliptin provided more effective glycemic control over 26 weeks compared with placebo or that, when coadministered with sitagliptin, provided more effective glycemic control compared with either agent alone …”

Practical Ways to Achieve Targets in Diabetes Care 2017

“…Each study underscored the SGLT‐2 inhibitor's efficacy. In the VERTIS FACTORIAL study, 1233 patients with type 2 diabetes (T2D) on stable metformin therapy were randomized to one of five arms: 5 mg ertugliflozin, 15 mg ertugliflozin, 100 mg sitagliptin (a dipeptidyl peptidase‐4 [DPP‐4] inhibitor branded as Januvia by Merck), a combination regimen of 5 mg ertugliflozin and 100 mg sitagliptin, or a combination regimen of 15 mg ertugliflozin and 100 mg sitagliptin. After 52 weeks, HbA1c declined by 1.4% from a baseline of 8.6% in both combination therapy groups compared with an HbA1c decline of approximately 1% from the same baseline in all monotherapy groups.…”