From the Guidelines
GLP-1 agonists are recommended for patients with reduced kidney function due to their favorable effects on kidney function and ability to slow the progression of diabetic kidney disease, as evidenced by the most recent study in 2025 1.
Key Points
- GLP-1 agonists, such as semaglutide, liraglutide, and dulaglutide, have demonstrated renoprotective effects in clinical studies and can be used safely in most patients with reduced kidney function 1.
- These medications protect the kidneys through multiple mechanisms, including reducing inflammation, decreasing oxidative stress, improving blood pressure control, and promoting weight loss, which indirectly benefits kidney function 1.
- Most GLP-1 agonists can be used without dose adjustment in mild to moderate kidney impairment (eGFR >30 mL/min/1.73m²), but caution is advised for severe kidney impairment (eGFR <30) 1.
- Patients should be monitored for potential side effects like nausea, vomiting, and diarrhea, which could potentially worsen dehydration in vulnerable patients with kidney disease, and adequate hydration should be maintained, especially when initiating therapy 1.
Benefits and Risks
- The benefits of GLP-1 agonists in patients with reduced kidney function include reducing albuminuria and slowing the progression of diabetic kidney disease, as well as reducing the risk of major adverse cardiovascular events (MACE) 1.
- The risks of GLP-1 agonists include nausea, vomiting, and diarrhea, which are common side effects, but are usually tolerable with dose titration and abate over several weeks to months 1.
Clinical Considerations
- For patients on dialysis, limited data exists, and individual risk-benefit assessment is necessary 1.
- GLP-1 agonists do not cause hypoglycemia per se, but when used with insulin or insulin secretagogues, doses of these drugs may be reduced to avoid hypoglycemia, especially in patients with moderate-to-severe CKD (CKD stages G3 and G4) 1.
From the FDA Drug Label
There have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis, in patients treated with GLP-1 receptor agonists. Some of these events have been reported in patients without known underlying renal disease A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Monitor renal function when initiating or escalating doses of OZEMPIC in patients reporting severe adverse gastrointestinal reactions.
Renal and urinary: Increased serum creatinine, acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis
GLP-1 agonists and kidney function: GLP-1 receptor agonists, such as semaglutide and liraglutide, may be associated with an increased risk of acute kidney injury and worsening of chronic renal failure.
- Patients without known underlying renal disease may also be at risk.
- Monitoring renal function is recommended when initiating or escalating doses of GLP-1 receptor agonists, especially in patients with severe gastrointestinal reactions.
- Dehydration and gastrointestinal symptoms may contribute to the development of acute kidney injury in patients treated with GLP-1 receptor agonists 2, 3.
From the Research
GLP-1 Agonists and Kidney Function
- GLP-1 receptor agonists (GLP-1 RAs) have been shown to have beneficial effects on kidney outcomes in patients with type 2 diabetes, including reducing albuminuria and slowing the decline in kidney function over time 4, 5, 6.
- The mechanisms underlying the effects of GLP-1 RAs on kidney function are thought to be mediated by natriuresis, anti-inflammatory and anti-oxidative stress properties, as well as suppression of renal fibrosis 7.
- Clinical trials have demonstrated that GLP-1 RAs have beneficial effects on renal outcomes, especially in patients with type 2 diabetes who are at high risk for cardiovascular disease 4, 6.
- GLP-1 RAs have been shown to be safe and effective in patients with different levels of kidney dysfunction, and may be particularly beneficial in patients with preexisting chronic kidney disease 6.
- The use of GLP-1 RAs in patients with chronic kidney disease and either overweight or obesity may also be beneficial, with potential improvements in metabolic control, weight, blood pressure, and kidney and cardiovascular outcomes 8.
Key Findings
- A pooled analysis of the SUSTAIN 6 and LEADER trials found that semaglutide and liraglutide lowered albuminuria by 24% versus placebo, and significantly slowed the decline in estimated glomerular filtration rate (eGFR) 6.
- The FLOW trial, which is studying the effects of semaglutide in patients with diabetic kidney disease, is expected to shed light on the effects of GLP-1 RAs on kidney outcomes and clarify their role in the management of patients with type 2 diabetes and kidney disease 4, 5.
- GLP-1 RAs have been shown to reduce the risk of persistent eGFR reductions, and may be particularly beneficial in patients with baseline eGFR <60 mL/min/1.73 m2 6.
Potential Benefits
- GLP-1 RAs may offer kidney-protective effects, which appear to be more pronounced in patients with preexisting chronic kidney disease 6.
- The use of GLP-1 RAs in patients with chronic kidney disease and either overweight or obesity may be beneficial, with potential improvements in metabolic control, weight, blood pressure, and kidney and cardiovascular outcomes 8.
- GLP-1 RAs may be a promising therapy for slowing the progression of diabetic chronic kidney disease, and may reduce the need for dialysis and kidney-disease related mortality in patients with kidney disease 5.