Introduction, study rationale, and design

• The Phase 3 VERTIS clinical trial program spans 9 clinical trials with about 13,000 patients in 40 countries
• The main goal of the trial was to assess the CV safety of ertugliflozin in patients with T2D and established atherosclerotic cardiovascular disease (ASCVD).
• Patients were randomized in a 1:1:1 fashion to ertugliflozin 5 mg (n=2,752), 15 mg (n=2,747), or matching placebo (n=2,747).
• The primary endpoint was a composite outcome of MACE (CV death, nonfatal myocardial infarction [MI], nonfatal stroke).
• Inclusion criteria were:
  • Age ≥40 years
  • HbA_1c 7.0-10.5% (53-91 mmol/mol)
  • Established ASCVD involving the coronary, cerebrovascular, and/or peripheral artery systems
  • Stable on antihyperglycemic agents (AHAs) or on no background AHA for ≥8 weeks prior to study participation

• Mean duration of follow-up was 3.5 years.

Baseline characteristics and metabolic results

• Baseline characteristics were well balanced between groups.
• Mean age was 64.4 years.
• 30% of participants were female.
• Baseline HbA_1c was 8.2%.
• Mean BMI was 32 kg/m².
• Almost all participants had a history of CV disease.
• Mean decrease in HbA_1c at 18 weeks for 5 mg ertugliflozin vs. placebo: -0.5% (p <0.001).
• Mean decrease in HbA_1c at 18 weeks for 15 mg ertugliflozin vs. placebo: -0.5% (p <0.001).
• Mean decrease in body weight for ertugliflozin 5 mg vs. placebo: 2.4 kg; for ertugliflozin 15 mg vs. placebo: 2.8 kg.

Cardiovascular and renal outcomes

• The primary outcome (CV death, nonfatal MI, or stroke) for ertugliflozin vs. placebo was 11.9% vs. 11.9% (HR 0.97, 95% CI 0.85-1.11, p < 0.001 for noninferiority).
• CV death for ertugliflozin vs. placebo was 1.8% vs. 1.9% (p=0.39).
• MI for ertugliflozin vs. placebo was 1.7% vs. 1.6% (p=0.66).
• Stroke for ertugliflozin vs. placebo was 0.8% vs. 0.8% (p=0.99).
• Hospitalization for heart failure for ertugliflozin vs. placebo was 2.5% vs. 3.6% (p=0.006).
• The renal composite endpoint (renal death, dialysis/transplant, doubling of serum creatinine) for ertugliflozin vs. placebo was 3.2% vs. 3.9% (p=0.08).
• Doubling of serum creatinine for ertugliflozin vs. placebo was 3.1% vs. 3.8%.

Safety results and updated cardiovascular meta-analysis

• Ertugliflozin was generally safe and well tolerated with a safety profile consistent with the known risks of SGLT2 inhibitors.
• Urinary tract infections and genital mycotic infections were slightly higher with ertugliflozin vs. placebo.
• An updated meta-analysis showed that the effects of SGLT2 inhibitors on CV and renal outcomes are largely consistent across the class.
• The greatest magnitude of benefit is for reduction in hospitalization for heart failure and kidney disease progression.