From the Guidelines
GLP-1 receptor agonists are recommended for patients with type 2 diabetes and proteinuria to reduce albuminuria and slow eGFR decline, as evidenced by recent studies 1. The use of GLP-1 receptor agonists, such as liraglutide, semaglutide, and dulaglutide, has been shown to have beneficial effects on kidney function, including reducing proteinuria and slowing the decline of estimated glomerular filtration rate (eGFR) 1. Some key points to consider when using GLP-1 receptor agonists for patients with proteinuria include:
- They reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes, with a greater reduction in risk for those with eGFR <60 ml/min/1.73 m2 1
- They decrease albuminuria and slow eGFR decline, as shown in cardiovascular outcomes trials and a clinical trial for glycemic efficacy and safety in patients with type 2 diabetes and eGFR 15–59 ml/min/1.73 m2 1
- The most common side effects are nausea, vomiting, and diarrhea, which occur in 15%–20% of patients with moderate-to-severe chronic kidney disease (CKD) but are usually tolerable with dose titration and abate over several weeks to months 1
- GLP-1 receptor agonist treatment is not recommended in patients at risk for thyroid C-cell tumors, pancreatic cancer, or pancreatitis based on theoretical risks from preclinical models 1
- GLP-1 receptor agonists that have shown cardiovascular and CKD benefits, such as liraglutide, semaglutide, and dulaglutide, are preferred agents 1 When initiating GLP-1 receptor agonist therapy, typical starting doses are semaglutide 0.25mg weekly (titrated up), dulaglutide 0.75mg weekly, or liraglutide 0.6mg daily (titrated up) 1. It is essential to use these medications cautiously in patients with severe kidney impairment (eGFR <30 ml/min/1.73m²) and dose adjustments may be necessary 1.
From the Research
GLP-1 and Proteinuria
- GLP-1 receptor agonists have been shown to reduce proteinuria in patients with type 2 diabetes 2, 3, 4.
- A study published in 2013 found that the GLP-1 receptor agonist liraglutide decreased proteinuria by 42% in patients with overt diabetic nephropathy 2.
- Another study published in 2022 found that semaglutide and liraglutide reduced albuminuria by 24% and slowed the decline of estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes 3.
- GLP-1 receptor agonists have also been shown to have kidney-protective effects, particularly in patients with preexisting chronic kidney disease 3, 4.
Mechanisms of Action
- GLP-1 receptor agonists have several mechanisms of action that may contribute to their kidney-protective effects, including:
- Augmentation of hyperglycemia-induced insulin secretion
- Suppression of glucagon secretion
- Deceleration of gastric emptying
- Reduction in calorie intake and body weight 5
- These mechanisms may help to reduce proteinuria and slow the progression of kidney disease in patients with type 2 diabetes.
Clinical Implications
- GLP-1 receptor agonists may be a useful treatment option for patients with type 2 diabetes and proteinuria 2, 3, 4.
- The kidney-protective effects of GLP-1 receptor agonists may be particularly beneficial for patients with preexisting chronic kidney disease 3, 4.
- Further research is needed to fully understand the clinical implications of GLP-1 receptor agonists in the treatment of proteinuria and kidney disease in patients with type 2 diabetes 6.