Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin

The VERTIS SITA2 placebo-controlled randomized study

Samuel Dagogo-Jack, Jie Liu, Roy Eldor, Guillermo Amorin, Jeremy Johnson, Darcy Hille, Yuqin Liao, Susan Huyck, Gregory Golm, Steven G. Terra, James P. Mancuso, Samuel S. Engel, Brett Lauring

Research output: Contribution to journalArticle

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Abstract

Aims: To assess ertugliflozin in patients with type 2 diabetes who are inadequately controlled by metformin and sitagliptin. Materials and Methods: In this double-blind randomized study (Clinicaltrials.gov NCT02036515), patients (glycated haemoglobin [HbA1c] 7.0% to 10.5% [53-91 mmol/mol] receiving metformin ≥1500 mg/d and sitagliptin 100 mg/d; estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2) were randomized to ertugliflozin 5 mg once-daily, 15 mg once-daily or placebo. The primary efficacy endpoint was change from baseline in HbA1c at Week 26; treatment was continued until Week 52. Results: A total of 464 patients were randomized (mean baseline HbA1c, 8.0% [64.3 mmol/mol]; eGFR, 87.9 mL/min/1.73 m2). After 26 weeks, placebo-adjusted least squares (LS) mean changes in HbA1c from baseline were −0.7% (−7.5 mmol/mol) and −0.8% (−8.3 mmol/mol) for ertugliflozin 5 and 15 mg, respectively (both P <.001); 17.0%, 32.1% and 39.9% of patients receiving placebo, ertugliflozin 5 mg or ertugliflozin 15 mg, respectively, had HbA1c <7.0% (53 mmol/mol). Significant reductions in fasting plasma glucose, body weight (BW) and systolic blood pressure (SBP) were observed with ertugliflozin relative to placebo. The positive effects of ertugliflozin on glycaemic control, BW and SBP were maintained through Week 52. A higher incidence of genital mycotic infections was observed in male and female patients receiving ertugliflozin (3.7%-14.1%) vs placebo (0%-1.9%) through Week 52. The incidence of urinary tract infections, symptomatic hypoglycaemia and hypovolaemia adverse events were not meaningfully different across groups. Conclusions: Ertugliflozin added to metformin and sitagliptin was well-tolerated, and provided clinically meaningful, durable glycaemic control, BW and SBP reductions vs placebo over 52 weeks.

Original languageEnglish (US)
Pages (from-to)530-540
Number of pages11
JournalDiabetes, Obesity and Metabolism
Volume20
Issue number3
DOIs
StatePublished - Mar 1 2018

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Metformin
Type 2 Diabetes Mellitus
Placebos
Safety
Blood Pressure
Body Weight
Glomerular Filtration Rate
5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-1-hydroxymethyl-6,8-dioxabicyclo(3.2.1)octane-2,3,4-triol
Sitagliptin Phosphate
Hypovolemia
Incidence
Glycosylated Hemoglobin A
Least-Squares Analysis
Hypoglycemia
Double-Blind Method
Urinary Tract Infections
Fasting
Glucose

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin : The VERTIS SITA2 placebo-controlled randomized study. / Dagogo-Jack, Samuel; Liu, Jie; Eldor, Roy; Amorin, Guillermo; Johnson, Jeremy; Hille, Darcy; Liao, Yuqin; Huyck, Susan; Golm, Gregory; Terra, Steven G.; Mancuso, James P.; Engel, Samuel S.; Lauring, Brett.

In: Diabetes, Obesity and Metabolism, Vol. 20, No. 3, 01.03.2018, p. 530-540.

Research output: Contribution to journalArticle

Dagogo-Jack, Samuel ; Liu, Jie ; Eldor, Roy ; Amorin, Guillermo ; Johnson, Jeremy ; Hille, Darcy ; Liao, Yuqin ; Huyck, Susan ; Golm, Gregory ; Terra, Steven G. ; Mancuso, James P. ; Engel, Samuel S. ; Lauring, Brett. / Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin : The VERTIS SITA2 placebo-controlled randomized study. In: Diabetes, Obesity and Metabolism. 2018 ; Vol. 20, No. 3. pp. 530-540.
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T1 - Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin

T2 - The VERTIS SITA2 placebo-controlled randomized study

AU - Dagogo-Jack, Samuel

AU - Liu, Jie

AU - Eldor, Roy

AU - Amorin, Guillermo

AU - Johnson, Jeremy

AU - Hille, Darcy

AU - Liao, Yuqin

AU - Huyck, Susan

AU - Golm, Gregory

AU - Terra, Steven G.

AU - Mancuso, James P.

AU - Engel, Samuel S.

AU - Lauring, Brett

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Aims: To assess ertugliflozin in patients with type 2 diabetes who are inadequately controlled by metformin and sitagliptin. Materials and Methods: In this double-blind randomized study (Clinicaltrials.gov NCT02036515), patients (glycated haemoglobin [HbA1c] 7.0% to 10.5% [53-91 mmol/mol] receiving metformin ≥1500 mg/d and sitagliptin 100 mg/d; estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2) were randomized to ertugliflozin 5 mg once-daily, 15 mg once-daily or placebo. The primary efficacy endpoint was change from baseline in HbA1c at Week 26; treatment was continued until Week 52. Results: A total of 464 patients were randomized (mean baseline HbA1c, 8.0% [64.3 mmol/mol]; eGFR, 87.9 mL/min/1.73 m2). After 26 weeks, placebo-adjusted least squares (LS) mean changes in HbA1c from baseline were −0.7% (−7.5 mmol/mol) and −0.8% (−8.3 mmol/mol) for ertugliflozin 5 and 15 mg, respectively (both P <.001); 17.0%, 32.1% and 39.9% of patients receiving placebo, ertugliflozin 5 mg or ertugliflozin 15 mg, respectively, had HbA1c <7.0% (53 mmol/mol). Significant reductions in fasting plasma glucose, body weight (BW) and systolic blood pressure (SBP) were observed with ertugliflozin relative to placebo. The positive effects of ertugliflozin on glycaemic control, BW and SBP were maintained through Week 52. A higher incidence of genital mycotic infections was observed in male and female patients receiving ertugliflozin (3.7%-14.1%) vs placebo (0%-1.9%) through Week 52. The incidence of urinary tract infections, symptomatic hypoglycaemia and hypovolaemia adverse events were not meaningfully different across groups. Conclusions: Ertugliflozin added to metformin and sitagliptin was well-tolerated, and provided clinically meaningful, durable glycaemic control, BW and SBP reductions vs placebo over 52 weeks.

AB - Aims: To assess ertugliflozin in patients with type 2 diabetes who are inadequately controlled by metformin and sitagliptin. Materials and Methods: In this double-blind randomized study (Clinicaltrials.gov NCT02036515), patients (glycated haemoglobin [HbA1c] 7.0% to 10.5% [53-91 mmol/mol] receiving metformin ≥1500 mg/d and sitagliptin 100 mg/d; estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2) were randomized to ertugliflozin 5 mg once-daily, 15 mg once-daily or placebo. The primary efficacy endpoint was change from baseline in HbA1c at Week 26; treatment was continued until Week 52. Results: A total of 464 patients were randomized (mean baseline HbA1c, 8.0% [64.3 mmol/mol]; eGFR, 87.9 mL/min/1.73 m2). After 26 weeks, placebo-adjusted least squares (LS) mean changes in HbA1c from baseline were −0.7% (−7.5 mmol/mol) and −0.8% (−8.3 mmol/mol) for ertugliflozin 5 and 15 mg, respectively (both P <.001); 17.0%, 32.1% and 39.9% of patients receiving placebo, ertugliflozin 5 mg or ertugliflozin 15 mg, respectively, had HbA1c <7.0% (53 mmol/mol). Significant reductions in fasting plasma glucose, body weight (BW) and systolic blood pressure (SBP) were observed with ertugliflozin relative to placebo. The positive effects of ertugliflozin on glycaemic control, BW and SBP were maintained through Week 52. A higher incidence of genital mycotic infections was observed in male and female patients receiving ertugliflozin (3.7%-14.1%) vs placebo (0%-1.9%) through Week 52. The incidence of urinary tract infections, symptomatic hypoglycaemia and hypovolaemia adverse events were not meaningfully different across groups. Conclusions: Ertugliflozin added to metformin and sitagliptin was well-tolerated, and provided clinically meaningful, durable glycaemic control, BW and SBP reductions vs placebo over 52 weeks.

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