From the Guidelines
GLP-1 agonists are recommended for patients with diabetes as they have been shown to reduce proteinuria and slow the decline of estimated glomerular filtration rate (eGFR), thereby improving kidney outcomes 1. The use of GLP-1 receptor agonists, such as liraglutide, semaglutide, and dulaglutide, has been associated with a reduced risk of major adverse cardiovascular events (MACE) and a slower decline in eGFR in patients with type 2 diabetes and chronic kidney disease (CKD) 1. Key benefits of GLP-1 agonists include:
- Reduced albuminuria and slower eGFR decline
- Lower risk of MACE
- Improved glycemic control
- Weight loss and reduced blood pressure
- Direct beneficial effects on the kidneys through GLP-1 receptors in renal tissue Common side effects of GLP-1 receptor agonists include nausea, vomiting, and diarrhea, but these are usually tolerable with dose titration and abate over time 1. The most recent and highest quality study suggests that GLP-1 receptor agonists, particularly liraglutide, semaglutide, and dulaglutide, are preferred agents for patients with type 2 diabetes and CKD due to their cardiovascular and CKD benefits 1. In clinical trials, GLP-1 agonists have demonstrated kidney benefits, including decreased albuminuria and slower decline in eGFR, compared to placebo, making them valuable for patients with type 2 diabetes who have or are at risk for diabetic kidney disease 1.
From the Research
GLP-1 Receptor Agonists and Proteinuria
- GLP-1 receptor agonists have been shown to have a positive effect on kidney outcomes in patients with type 2 diabetes, including reducing albuminuria and proteinuria 2, 3.
- A pooled analysis of the SUSTAIN 6 and LEADER trials found that semaglutide and liraglutide lowered albuminuria by 24% compared to placebo, with significant reductions in eGFR slope decline and risk of persistent eGFR reduction 2.
- A systematic review and meta-analysis of randomized trials found that long-acting GLP-1 receptor agonists reduced the incidence of major adverse cardiovascular events, hospitalization for heart failure, and a composite kidney outcome, including kidney failure and sustained eGFR decline 3.
- The mechanisms by which GLP-1 receptor agonists exert their kidney-protective effects are not fully understood, but may involve improvements in glucose control, blood pressure reduction, and anti-inflammatory effects 4, 2.
Key Findings
- GLP-1 receptor agonists have been shown to reduce albuminuria and proteinuria in patients with type 2 diabetes 2, 3.
- The kidney-protective effects of GLP-1 receptor agonists appear to be more pronounced in patients with preexisting chronic kidney disease 2.
- Long-acting GLP-1 receptor agonists, including both injectable and oral formulations, have been shown to reduce the incidence of major adverse cardiovascular events, hospitalization for heart failure, and kidney events 3.
Comparison with Other Therapies
- SGLT-2 inhibitors have also been shown to have renoprotective effects, including reducing albuminuria and proteinuria in patients with type 2 diabetes 5.
- The choice of therapy for patients with type 2 diabetes and kidney disease should be individualized, taking into account the patient's specific needs and risk factors 4, 3.