Once-Weekly Tirzepatide Versus Dulaglutide for

Tirzepatide and Cardiovascular Outcomes Tirzepatide is a dual agonist at the GLP-1 and GIP receptors with incremental benefits on glycemic control, weight loss and associated metabolic risk factors in comparison with selective GLP-1RAs
Tirzepatide produced favorable effects on quality of life, six-minute walk distance and the composite of cardiovascular death or heart failure events in patients with HFpEF and obesity
SURPASS-CVOT demonstrated that tirzepatide was non-inferior to dulaglutide and superior to a putative placebo on MACE
This pre-specified analysis investigated outcomes in patients with and without a prior history of heart failure<br>

Study Design Key Inclusion Criteria
≥40 years
Diagnosis of type 2 diabetes
Established ASCVD
HbA1c ≥7% and ≤10.5%
Body mass index ≥25 kg/m2<br>

SURPASS-CVOT Heart Failure Outcomes SURPASS-CVOT:
Tirzepatide vs. Dulaglutide Indirect Comparison:
Tirzepatide vs. Placebo<br>

SURPASS-CVOT Mortality Outcomes All-Cause Mortality Non-Cardiovascular Death<br>

Baseline Characteristics<br>

Baseline Medication Use<br>

Baseline Metabolic Risk Factors<br>

Change from Baseline in HbA1c and Body Weight<br>

Change from Baseline in Systolic Blood Pressure and eGFR<br>

Composite Heart Failure Endpoints All-Cause Death or Hospitalization or Urgent Visits for Heart Failure CV Death or Hospitalization or Urgent Visits for Heart Failure<br>

All-Cause Mortality and Heart Failure Events All-Cause Mortality Hospitalization or Urgent Visits for Heart Failure<br>

Key Clinical Endpoints<br>

Change from Baseline in eGFR in High and Very-High Risk CKD<br>

SGLT2 Inhibitor Initiation Post-Baseline<br>

Patient Reported Outcomes: Transformed Total Score of APPADL at Baseline and Month 48<br>

Patient Reported Outcomes: EQ-5D-5L VAS Score at Baseline and Month 48<br>

Safety Overview<br>

Limitations SURPASS-CVOT demonstrated non-inferiority for the primary endpoint and all subsequent analyses should be considered exploratory
SURPASS-CVOT was not a heart failure trial, accordingly ejection fraction, BNP levels or underlying cause of heart failure is not known
The impact of disproportionately greater use of SGLT2 inhibitors during the trial in the dulaglutide group remains to be determined
The profile of sex, race and geographical representation of patients may limit the generalizability of the findings
The mechanism underlying potential benefits of incretin targeted agents on HF outcomes remains to be determined
SURPASS-CVOT was an active comparator trial and did not involve a direct comparison with placebo<br>

Conclusions Treatment with tirzepatide:
was non-inferior compared with dulaglutide on the composite endpoint of cardiovascular death and HF events
was superior to both a putative placebo and indirect comparison with placebo treated patients from REWIND on the composite endpoint of cardiovascular death and HF events
was superior to dulaglutide on the composite endpoint of all-cause death and HF events in patients with and without a prior history of HF
had favorable effects on HbA1c, body weight, blood pressure and eGFR compared with dulaglutide in patients with and without a prior history of HF
Safety outcomes were similar in the tirzepatide and dulaglutide groups, however an increase in GI adverse events was observed with TZP in patients with and without a prior history of HF
Overall, SURPASS-CVOT demonstrated potentially favorable effects of TZP on HF outcomes in patients with and without a prior history of HF<br>

Final Comment The finding that tirzepatide was comparable to dulaglutide on a range of cardiovascular outcomes and had favorable effects on mortality and an expanded MACE endpoint including coronary revascularization in patients with and without a history of heart failure further establishes this as a potential therapeutic option for the treatment of patients with type 2 diabetes and atherosclerotic cardiovascular disease<br>