Liraglutide and Renal Outcomes in Type 2 Diabetes

Abstract

This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).

Effects of Diabetes Medications Targeting the Incretin System on the Kidney

“…This benefit was driven by a 26% reduction in new-onset macroalbuminuria (HR, 0.74; 95% CI, 0.60 to 0.91; P50.004). The rate of decline in eGFR during the study was also modestly lower in participants receiving liraglutide compared with the placebo group (27.4 versus 27.8 ml/min per 1.73 m 2 over 36 months; P50.01), especially in participants with stage 3 or 4 CKD at baseline (5). However, the number of participants who experienced a persistent doubling of serum creatinine level and an eGFR#45 ml/min per 1.73 m 2 was unaffected (HR, 0.89; 95% CI, 0.67 to 1.19; P50.43), and no changes were observed in the incidence of ESRD (5).…”

“…Reductions in insulin, body weight, and BP may also have benefits in the kidney. Nonetheless, sensitivity analysis from the LEADER Trial suggests that the effects of liraglutide were partly independent of improvement in glycemic control (20.4% hemoglobin A1c) and body weight (22.3 kg) between the two study arms (5). Equally, the clear reduction in albuminuria in the AWARD-7 Trial, in which glycemic equipoise was achieved (9), seems consistent with glucose-independent actions on CKD in type 2 diabetes.…”

“…In the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome (LEADER) Trial, the effects of daily injections of the GLP-1RA liraglutide were examined in 9340 subjects with type 2 diabetes at high risk for CVD (5). Over a median follow-up of 3.8 years, participants receiving liraglutide experienced a 22% reduction (hazard ratio [HR], 0.78; 95% confidence interval [95% CI], 0.67 to 0.92; P50.003) in the prespecified kidney outcome, a composite of time to the development of newonset persistent macroalbuminuria, persistent doubling of serum creatinine and eGFR,45 ml/min per 1.73 m 2 , ESRD, and death due to CKD.…”

Empagliflozin reduces albuminuria—a promise for better cardiorenal protection from the EMPA-REG OUTCOME trial

“…So far, only liraglutide has shown renal benefit in a large outcome trial. In a secondary analysis of the LEADER trial (20), a lower proportion of liraglutide treated patients displayed progression to macroalbuminuria, making up the major part of the combined renal endpoint which occurred in 15 versus 19 patients per 1,000 patient-years of observation in the liraglutide and the placebo group, respectively.…”

Key Updates in Cardio-Nephrology from 2018: Springboard to a Bright Future

“…The Liraglutide and Renal Outcomes in Diabetes trial reported on the composite renal outcome occurring in fewer participants in the liraglutide group than in the placebo group (HR = 0.78; 95% CI 0.67–0.92). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; HR = 0.74; 95% CI 0.60–0.91) [18]. A recent post hoc analysis of the Liraglutide Effect and Action in Diabetes (LEADER) trial reported that in patients with eGFR < 60 mL/min/1.73 m 2 the risk reduction for the primary composite cardiovascular outcome with liraglutide was greater (HR = 0.69; 95% CI 0.57–0.85) versus those with eGFR ≥60 mL/min/1.73 m 2 (HR = 0.94; 95% CI 0.83–1.07) [19].…”