LEADER
Trial question
What is the effect of liraglutide in patients with T2DM and high cardiovascular risk?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
36.0% female
64.0% male
N = 9340
9340 patients (3337 female, 6003 male).
Inclusion criteria: patients with T2DM who had a glycated hemoglobin level of ≥ 7.0% and high cardiovascular risk.
Key exclusion criteria: T1DM, calcitonin ≥ 50 ng/L, chronic HF, current continuous RRT, ESRD, history of solid organ transplant or awaiting solid organ transplant, malignant neoplasm, personal history of non-familial medullary thyroid carcinoma.
Interventions
N=4668 liraglutide (1.8 mg or maximum tolerated dose once daily as a subcutaneous injection in addition to standard care).
N=4672 placebo (matching placebo once daily as a subcutaneous injection in addition to standard care).
Primary outcome
CV death, nonfatal MI, or nonfatal stroke
13%
14.9%
14.9 %
11.2 %
7.5 %
3.7 %
0.0 %
Liraglutide
Placebo
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in CV death, nonfatal MI, or nonfatal stroke (13% vs. 14.9%; HR 0.87, 95% CI 0.78 to 0.97).
Secondary outcomes
Significant decrease in death due to cardiovascular causes (4.7% vs. 6%; HR 0.78, 95% CI 0.66 to 0.93).
Safety outcomes
No significant differences in adverse events (62.3% vs. 60.8%, p=0.12) and serious adverse events (49.7% vs. 50.4%, p=0.51).
Significant differences in adverse event leading to discontinuation of trial regimen (9.5% vs. 7.3%, p < 0.001) and acute gallstone disease (3.1% vs. 1.9%, p < 0.001).
Conclusion
In patients with T2DM who had a glycated hemoglobin level of ≥ 7.0% and high cardiovascular risk, liraglutide was noninferior to placebo with respect to CV death, nonfatal MI, or nonfatal stroke.
Reference
Steven P Marso, Gilbert H Daniels, Kirstine Brown-Frandsen et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):311-22.
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