Ertugliflozin and Sitagliptin Co-initiation in Patients with Type 2 Diabetes: The VERTIS SITA Randomized Study

Sam Miller, Tania Krumins, Haojin Zhou, Susan Huyck, Jeremy Johnson, Gregory Golm, Steven G Terra, James P Mancuso, Samuel S Engel, Brett Lauring, Sam Miller, Tania Krumins, Haojin Zhou, Susan Huyck, Jeremy Johnson, Gregory Golm, Steven G Terra, James P Mancuso, Samuel S Engel, Brett Lauring

Abstract

Introduction: Ertugliflozin is an oral sodium-glucose cotransporter 2 inhibitor that is being developed to treat type 2 diabetes mellitus (T2DM). This study assessed the efficacy and safety of co-initiation of ertugliflozin and sitagliptin compared with placebo in patients with T2DM inadequately controlled on diet and exercise.

Methods: In this phase III, randomized, double-blind, multicenter, placebo-controlled 26-week study (NCT02226003), patients with T2DM and glycated hemoglobin (HbA1c) 8.0-10.5% on diet/exercise were randomized 1:1:1 to ertugliflozin 5 mg once daily (QD) and sitagliptin 100 mg QD (E5/S100), ertugliflozin 15 mg QD and sitagliptin 100 mg QD (E15/S100), or placebo. The primary efficacy endpoint was the change from baseline in HbA1c at week 26.

Results: The mean baseline HbA1c of the randomized patients (n = 291) was 8.9%. At week 26, both ertugliflozin/sitagliptin treatments provided significant reductions from baseline in HbA1c compared with placebo [least squares mean HbA1c change (95% confidence intervals) from baseline was - 0.4% (- 0.7, - 0.2), - 1.6% (- 1.8, - 1.4), and - 1.7% (- 1.9, - 1.5) for placebo, E5/S100, and E15/S100, respectively]. At week 26, 8.3%, 35.7%, and 31.3% of patients receiving placebo, E5/S100, and E15/S100, respectively, had HbA1c < 7.0%. Significant reductions in fasting plasma glucose, 2-h post-prandial glucose, body weight, and systolic blood pressure were observed with both ertugliflozin/sitagliptin groups compared with placebo. The incidence of adverse events (AEs) was similar across the groups. The incidences of the pre-specified AEs of urinary tract infection, genital mycotic infection, symptomatic hypoglycemia, and hypovolemia were low and not meaningfully different across groups.

Conclusion: Co-initiation of ertugliflozin with sitagliptin in patients with T2DM inadequately controlled on diet and exercise provided a clinically meaningful improvement in glycemic control over 26 weeks.

Clinical trial registration: Clinicaltrials.gov NCT02226003.

Keywords: Ertugliflozin; Glycemic control; SGLT2 inhibitor; Sitagliptin; Type 2 diabetes mellitus.

Figures

Fig. 1
Fig. 1
Change over time in a glycated hemoglobin (HbA1c), b body weight, and c systolic blood pressure (SBP)a. LS least squares, SE standard error. a Relevant p values are provided in Tables 2 and 3
Fig. 2
Fig. 2
a Mean change from baseline in estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2) through week 26. b Mean change from baseline in serum creatinine (mg/dL) through week 26. SE standard error

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