VERTIS CV Trial: Ertugliflozin Effect on CV Outcomes in Type 2 Diabetes

VERTIS CV Trial

VERTIS CV Trial: The SGLT-2 inhibitors are the next generation drugs for type 2 diabetes as well as patients with heart failure. We have seen a surge of these drugs in last 5 years. Emagliflozin and dapagliflozin are already being widely used for DM2 as well as patients with heart failure with or without DM2. Ertugliflozin is the next in line SGLT2 inhibitor that has shown to be relatively more efficacious in terms of decreasing HbA1c. Indirect comparisons for HbA1c reduction found that ertugliflozin 5 mg was more effective than dapagliflozin 5 mg when added to metformin monotherapy, whereas ertugliflozin 15 mg was more effective than dapagliflozin 10 mg and empagliflozin 25 mg when added to diet/exercise and to metformin monotherapy. (source)

Clinical Question of the VERTIS CV trial:

To evaluate the long-term effects of ertugliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes..

Bottom Line:

Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, ertugliflozin was shown to have safe profile with respect to major adverse cardiovascular events and was noninferior to placebo.

Trial Design:

Randomized, double-blind, parallel-group, placebo-controlled trial

Population:

In total, 8246 patients were included and were randomized to ertugliflozin (N=5493) divided 1:1 between 5 mg or 15 mg ertugliflozin or placebo (N=2745)

Inclusion Criteria:

  • Patients were eligible if they were at least 40 years of age and had type 2 diabetes (HbA1c of 7.0 to 10.5%) and established atherosclerotic cardiovascular disease involving the coronary, cerebrovascular, or peripheral arterial systems.

Exclusion Criteria:

  • Key exclusion criteria were a history of type 1 diabetes or ketoacidosis and an estimated GFR below 30.

Primary Outcomes:

  1. Death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke %

11.9% patients in the ertugliflozin had primary endpoint event compared to 11.9% in the placebo group showing noninferiority
HR 0.97; 95% CI, 0.85 to 1.11; P<0.001 for noninferiority

Key Secondary Outcomes:

1. Death from cardiovascular causes or hospitalization for heart failure %

8.1% (ertugliflozin) vs 9.1% (placebo)
HR 0.70; 95% CI, 0.58 to 0.85; P<0.001

2. Death from renal causes, renal replacement therapy, or doubling of the serum creatinine level

3.2% (ertugliflozin) vs. 3.9% (placebo)
(HR 0.81 CI 95% 0.63–1.04)

3. Death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina
15% vs. 16% 
(HR 0.92 CI 95%, 0.82–1.04)

Take Home Point:

Ertugliflozin has known to decrease HbA1c further but based on the active trial results major adverse cardiac event reductions were statistically significant only for canagliflozin and empagliflozin. Ertugliflozin showed statistically significant superiority to placebo for just one endpoint, hospitalization for heart failure, making it probably not the firstline choice in comparison to other SGLT2 inhibitors.

Source: NEJM