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Cardiovascular and renal outcomes by baseline albuminuria status and renal function: Results from the LEADER
Ofri Mosenzon1, Stephen C Bain2, Hiddo J L Heerspink3,4
1Diabetes Unit, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.
Insights
In patients with type 2 diabetes, higher urinary albumin-to-creatinine ratio (UACR) and lower estimated glomerular filtration rate (eGFR) indicate increased cardiorenal risks. Liraglutide showed similar or lower risks across subgroups.
Area of Science:
- Cardiology
- Nephrology
- Endocrinology
Background:
- Cardiorenal outcomes are critical in type 2 diabetes.
- Urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are key indicators of kidney function.
- The LEADER trial evaluated liraglutide in high cardiovascular risk patients with type 2 diabetes.
Purpose of the Study:
- To assess cardiorenal outcomes based on baseline UACR and eGFR in the LEADER trial cohort.
- To investigate the impact of UACR and eGFR on major adverse cardiovascular events and renal outcomes.
- To evaluate the efficacy of liraglutide in different UACR and eGFR subgroups.
Main Methods:
- The LEADER trial was a multinational, double-blind study comparing liraglutide to placebo in type 2 diabetes patients.
- Patients were randomized and followed for 3.5 to 5 years.
- Post hoc Cox regression analyses examined outcomes across baseline UACR and eGFR subgroups.
Main Results:
- Increasing UACR and decreasing eGFR were significantly associated with higher risks of primary composite outcomes, heart failure hospitalization, renal events, and death.
- P-values for trends across subgroups were <.0001.
- Liraglutide demonstrated generally lower or similar risks of cardiorenal events and death compared to placebo across all UACR and eGFR subgroups.
Conclusions:
- In type 2 diabetes, baseline UACR and eGFR are strong predictors of cardiorenal events and mortality.
- Liraglutide appears to offer cardiorenal benefits or is non-inferior to placebo across a spectrum of kidney function and albuminuria.
- These findings highlight the importance of assessing UACR and eGFR for risk stratification and treatment decisions in type 2 diabetes.
Aim:
To assess cardiorenal outcomes by baseline urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) in the contemporary LEADER cohort.
Materials And Methods:
LEADER was a multinational, double-blind trial. Patients with type 2 diabetes and high cardiovascular (CV) risk were randomized 1:1 to the glucagon-like peptide-1 analogue liraglutide (≤1.8 mg daily; n = 4668) or placebo (n = 4672) plus standard care and followed for 3.5 to 5 years. Primary composite outcomes were time to first non-fatal myocardial infarction, non-fatal stroke or CV death. Post hoc Cox regression analyses of outcomes by baseline UACR and eGFR subgroups were conducted with adjustment for baseline variables.
Results:
In the LEADER population, 1598 (17.5%), 2917 (31.9%), 1200 (13.1%), 1611 (17.6%), 845 (9.2%) and 966 (10.6%) had UACR = 0, >0 to <15, 15 to <30, 30 to <100, 100 to <300 and ≥300 mg/g, respectively. Increasing UACR and decreasing eGFR were linked with higher risks of the primary outcome, heart failure hospitalization, a composite renal outcome and death (P-values for the Cochran-Armitage test for trends were all <.0001). Across UACR and eGFR subgroups, risks of cardiorenal events and death were generally lower or similar with liraglutide versus placebo.
Conclusions:
In a contemporary type 2 diabetes population, increasing baseline UACR and declining eGFR were linked with higher risks of cardiorenal events and death.
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