Clinical Trial Vertis

STEGLATRO has been evaluated in several Phase 3 studies involving patients with T2DM

Add-on to Diet and Exercise	Add-on to MET	Add-on to Dual Combination	Special Population
VERTIS MONO1 ERTU Monotherapy N=461 View Study Below	VERTIS MET3 ERTU added to MET N=621 View Study Below	VERTIS SITA24 ERTU vs. Placebo N=464 View Study Below	VERTIS CV5 CV Outcomes Trial N= 8,246
	VERTIS SU2 ERTU vs. Glimepiride N=1,326
			VERTIS RENAL6 ERTU vs. Placebo N=468	VERTIS ASIA7 ERTU added to MET N=465

VERTIS MONO Study design¹

A total of 461 patients with type 2 diabetes inadequately controlled on diet and exercise participated in a randomised, double-blind, 26-week, placebo-controlled study to evaluate the efficacy and safety of ertugliflozin monotherapy. These patients, who were not receiving any background antihyperglycaemic treatment for ≥8 weeks, were randomised to ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo administered once daily. The primary endpoint was the change in HbA1c from baseline to week 26.

VERTIS MET Study design³

A total of 621 patients with type 2 diabetes mellitus (T2DM) participated in a randomised, multicentre, parallel-group study to evaluate the efficacy and safety of ertugliflozin 5 or 15 mg in patients with T2DM and on metformin (MET) monotherapy.

The double-blind treatment period was 104 weeks in duration and divided into 2 phases (phase A: weeks 1–26; phase B: weeks 27–104, a 78-week extension period during which the placebo group received blinded glimepiride [if not rescued during phase A]).

The study population included patients ≥18 years of age with T2DM and HbA1c ≥7.0% and ≤10.5% on MET monotherapy (≥1,500 mg/d for ≥8 weeks) and with a body mass index (BMI) 18.0–40.0 kg/m^².

Patients were randomized in a 1:1:1 manner to ertugliflozin 5 mg (n=207), ertugliflozin 15 mg (n=205), or placebo (n=209) administered once daily in addition to continuation of background MET therapy.

Glycaemic rescue therapy (open-label glimepiride in phase A/blinded glimepiride in phase B if not rescued in phase A) was initiated for patients who met progressively stricter glycaemic thresholds during the trial.

The primary efficacy end point was change from baseline at week 26 in HbA1c. Prespecified secondary efficacy end points were changes from baseline at week 26 in fasting plasma glucose, body weight, and systolic and diastolic blood pressure. Participants with HbA1c <7.0% at week 26 and proportions of those who received glycaemic rescue therapy were also evaluated.

Safety assessments included adverse event (AE) monitoring. Prespecified AEs included symptomatic hypoglycaemia and AEs associated with genital mycotic infection, urinary tract infection, and hypovolaemia.

VERTIS SITA2 Study design⁴

A total of 464 patients with type 2 diabetes mellitus on metformin ≥1,500 mg/day and sitagliptin 100 mg/day participated in a randomised, multicentre, parallel-group study to evaluate the efficacy and safety of ertugliflozin as add-on therapy. A total of 462 patients were analysed (2 patients in the ertugliflozin 15-mg group did not receive study medication).

The double-blind treatment period was 52 weeks in duration and divided into two 26- week phases (phase A: weeks 1–26; phase B: weeks 27–52).

Patients on ≥1,500 mg/day metformin and sitagliptin 100 mg/day for ≥8 weeks with HbA1c ≥7.0% and ≤10.5% at screening were eligible to directly enter a placebo run-in period.

Patients on therapy for <8 weeks, on metformin <1,500 mg/day, on a dipeptidyl peptidase 4 inhibitor other than sitagliptin, or on a sulfonylurea were put on the appropriate treatments through wash-off (and titration where appropriate) and dose stabilisation prior to the placebo run-in period.

Patients were randomised in a 1:1:1 manner to ertugliflozin 5 mg (n=156), ertugliflozin 15 mg (n=155), or placebo (n=153) administered once daily in addition to continuation of background metformin and sitagliptin therapy. 464 patients were randomised and 462 were analysed (2 patients in the ertugliflozin 15 mg group did not receive study medication).

The primary efficacy end point was change from baseline in HbA1c at week 26.

Key secondary efficacy end points were change from baseline at week 26 in fasting plasma glucose, body weight, and systolic blood pressure, and the proportion of patients with HbA1c <7.0% at week 26.

Efficacy assessments were also performed at week 52, though no formal hypothesis testing was conducted.

Safety analysis was conducted at week 26 (phase A) and week 52 (phase A+B). Safety assessments included the number of patients with adverse events (AEs), including AEs prespecified for inferential testing (symptomatic hypoglycaemia, AEs associated with genital mycotic infection, urinary tract infection, and hypovolemia).