From the Guidelines
Semaglutide should be considered for patients with non-diabetic proteinuric kidney disease due to its potential renal protective effects, as evidenced by its ability to reduce albuminuria and slow eGFR decline, as seen in cardiovascular outcomes trials and a clinical trial for glycemic efficacy and safety in patients with T2D and eGFR 15–59 ml/min/1.73 m2 1.
Key Considerations
- The use of semaglutide in non-diabetic proteinuric kidney disease is not currently FDA-approved, but emerging research suggests it may offer benefits in this population.
- Standard treatment should continue with ACE inhibitors or ARBs as first-line therapy, along with SGLT2 inhibitors which have established renal protective effects.
- If considering semaglutide off-label, it would typically be initiated at 0.25 mg subcutaneously once weekly for 4 weeks, then increased to 0.5 mg weekly, with potential further titration to 1 mg weekly based on tolerance and response.
Mechanisms and Benefits
- The potential renal benefits of semaglutide likely stem from multiple mechanisms including improved glycemic control, weight reduction, decreased inflammation, and direct effects on the kidney's GLP-1 receptors which may reduce hyperfiltration, oxidative stress, and fibrosis 1.
- GLP-1 receptor agonists, including semaglutide, have been shown to reduce the risk of major adverse cardiovascular events (MACE) in patients with T2D, and this benefit may also extend to patients with non-diabetic kidney disease 1.
Monitoring and Side Effects
- Patients should be monitored for changes in proteinuria, kidney function (eGFR), and side effects such as nausea, vomiting, and diarrhea.
- The most common side effects of GLP-1 receptor agonists, including semaglutide, are nausea, vomiting, and diarrhea, which occur in 15%–20% of patients with moderate-to-severe CKD, but are usually tolerable with dose titration and abate over several weeks to months 1.
From the Research
Semaglutide in Non-Diabetic Proteinuric Kidney Disease
- There is no direct evidence on the use of semaglutide in non-diabetic proteinuric kidney disease in the provided studies.
- However, the studies discuss the treatment and management of proteinuric and non-proteinuric kidney diseases, including diabetic kidney disease 2, 3, 4, 5, 6.
- The use of ACE inhibitors and ARB therapy has been shown to decrease urinary protein excretion and slow the progression of both diabetic and non-diabetic proteinuric renal disease 2.
- Non-proteinuric renal diseases are the leading cause of end-stage kidney disease, and research efforts are needed to develop treatment strategies for these diseases 3.
- SGLT2 inhibitors have been shown to reduce albuminuria in macro and microalbuminuric patients and may have a favorable impact on the progression of diabetic kidney disease in nonalbuminuric diabetic people 4.
- Patients with nonproteinuric diabetic kidney disease have better-controlled blood pressure and fewer typical morphological changes and are at lower risk of CKD progression and all-cause mortality 5.
Treatment Options
- ACE inhibitors and ARB therapy may be used to decrease urinary protein excretion and slow the progression of proteinuric renal disease 2.
- SGLT2 inhibitors may be used to reduce albuminuria and slow the progression of diabetic kidney disease in nonalbuminuric diabetic people 4.
- However, there is no direct evidence on the use of semaglutide in non-diabetic proteinuric kidney disease, and further research is needed to determine its efficacy and safety in this population.