Kidney Week Educational Symposia-Glucagon-Like Peptide-1 Receptor Agonists and Diabetic Kidney Disease

Video Transcription

Video Summary

The session reviews the growing role of GLP‑1 receptor agonists (GLP‑1RAs) in diabetic kidney disease (DKD) within the broader “cardio‑kidney‑metabolic” framework. The moderator introduces DKD as a leading cause of kidney failure and mortality, emphasizing that newer therapies (SGLT2 inhibitors, GLP‑1RAs, finerenone) provide benefits beyond glucose lowering, likely involving inflammation, mitochondrial dysfunction, and altered nutrient metabolism. The history of GLP‑1 discovery and drug development is summarized, highlighting its pleiotropic effects and expanding indications.<br /><br />Dr. Rossing focuses on clinical outcomes. Earlier cardiovascular outcome trials suggested kidney benefit mainly through reduced albuminuria, with less certainty for GFR preservation. This led to the dedicated FLOW trial in type 2 diabetes with CKD (eGFR 25–75 plus albuminuria), testing semaglutide 1 mg vs placebo on background standard care. FLOW was stopped early for efficacy and showed significant reductions in a composite kidney endpoint, slower kidney function decline, fewer major adverse cardiovascular events, and lower all‑cause mortality in a very high‑risk population. Data suggest benefits are additive with SGLT2 inhibitors and support a “four pillars” approach (RAS blockade, SGLT2 inhibitor, MRA, GLP‑1RA). SELECT (obesity without diabetes) also suggests potential kidney benefit, mainly via albuminuria and slope effects.<br /><br />Dr. Alichich reviews mechanisms: GLP‑1 is produced peripherally and centrally; receptors are present in kidney (proximal tubule, smooth muscle) and immune cells. Benefits are only partly explained by glucose, weight loss, and blood pressure. Emerging work highlights immunomodulatory and anti‑inflammatory actions, microbiome interactions, and downregulation of RAGE signaling, with supportive animal data and ongoing human mechanistic studies.<br /><br />Q&A addresses additivity with other therapies, receptor biology (single GLP‑1 receptor), future trials in dialysis/transplant populations, and broader calls for kidney regeneration research.

Asset Subtitle

Moderator(s): Subramaniam Pennathur

Presentation(s):

Introduction - Subramaniam Pennathur
GLP-1 RAs in Diabetic Kidney Disease: Focus on Kidney Outcomes - Peter Rossing
GLP-1 RAs: On the Mechanisms of Renoprotection - Radica Alicic

Support is provided by an educational grant from Novo Nordisk.

Meta Tag

Date 10/26/2024

Pathway 1 Diabetic Kidney Disease

Pathway 2 CKD Non-Dialysis

Session ID 494159

Session Type ES - Educational Symposium

Keywords

GLP-1 receptor agonists

diabetic kidney disease

cardio-kidney-metabolic framework

FLOW trial

semaglutide

SGLT2 inhibitors

finerenone

albuminuria reduction

eGFR decline

anti-inflammatory mechanisms