Decreased UARC Linked to Reduced Risk for Cardiovascular, Renal Events in T2D

A reduction in urinary albumin-to-creatinine ratio (UACR) over a 1-year period is associated with a decreased risk for cardiovascular and renal events, according to the results of a study published in Diabetes Care.

Studies have shown that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have both cardiovascular and renal benefits in patients with type 2 diabetes (T2D) and elevated cardiovascular risk. However, whether a reduction in these patients’ UACR is associated with a reduction in the risk of future cardiovascular and renal events in those treated with a GLP-1 RA had not yet been established.

To evaluate this association, data from 8,270 participants (35.5% women) with T2D and high cardiovascular risk were analyzed. Individuals were randomly assigned to receive either daily subcutaneous liraglutide (1.8 mg or the maximum tolerated dose) or a matching placebo, while maintaining their standard-of-care therapy. Most participants (>80%) used renin-angiotensin-aldosterone system (RAAS) inhibitors as part of their standard-of care-therapy, more than 40% used insulin, 88% used glucose-lowering agents, and 76% used lipid-lowering agents.

The primary outcome was the time from randomization to the first occurrence of a composite of major adverse cardiovascular events (MACE). The secondary outcome was the time from randomization to nephropathy. UACR and serum creatinine levels were measured at the time of randomization and annually thereafter.

Half of participants experienced an increase in albuminuria during the first year. More than one-third of participants (35%) experienced a reduction of more than 30% in UACR from baseline. On average, individuals who received liraglutide experienced a 15% reduction in UACR from baseline, compared with a 10% increase in the placebo group.

Individuals who experienced a UACR reduction of more than 30% had a significant decrease in risk for MACE (P =.006) and nephropathy (P=.02). Among individuals who had a UACR reduction of more than 30%, no significant difference in risk for MACE or nephropathy was observed between individuals who received liraglutide and those who did not.

Among individuals who experienced a reduction of UACR of more than 30%, those who received liraglutide experienced a significant reduction in risk for nephropathy, whereas individuals who did not receive liraglutide did not. A significant decrease in the risk for MACE was observed in individuals who had microalbuminuria or macroalbuminuria at baseline who experienced a decrease in UACR of more than 30%.

These findings indicated that a reduction in UACR in a 1-year period predicts a reduced risk for major cardiovascular and renal outcomes. Though liraglutide administration was more likely to result in a significant reduction in UACR (>30%) than placebo, a reduction in UACR without liraglutide was still associated with a decreased risk for MACE and renal outcomes.

Limitations of this study include its post hoc nature, which prevents causal inference. Additionally, the inclusion of individuals with T2D and high cardiovascular risk may preclude the results of this study from being generalizable to the population at large. The reliance on a single urine sample for UACR measurement may have resulted in more variance than if an average of multiple measurements had been used.

Future research investigating the underlying mechanism by which albuminuria impacts health is warranted.

Disclosures: Several study authors have declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Persson F, Baini SC, Mosenzon O, et al. “Changes in Albuminuria Predict Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Post Hoc Analysis of the LEADER Trial.” Diabetes Care. Published online January 27, 2021. doi:10.2337/dc20-1622