Which Glucagon-like peptide (GLP) drug has evidence in chronic kidney disease?

GLP-1 Receptor Agonists in Chronic Kidney Disease

Dulaglutide, liraglutide, and injectable semaglutide are the preferred GLP-1 receptor agonists for patients with chronic kidney disease due to their demonstrated cardiovascular benefits and favorable effects on kidney outcomes. 1

Evidence for GLP-1 RAs in CKD

GLP-1 receptor agonists have shown significant benefits in patients with chronic kidney disease:

• Renal Benefits:

  • Reduce albuminuria and slow eGFR decline 1
  • Can be used in patients with eGFR as low as 15 ml/min/1.73 m² 1
  • Significantly reduce risk for composite kidney disease outcomes (macroalbuminuria, eGFR decline, progression to kidney failure, or death from kidney disease) 1

• Cardiovascular Benefits:

  • Reduce major adverse cardiovascular events (MACE) 1
  • MACE risk reduction with liraglutide was significantly greater for those with eGFR <60 ml/min/1.73 m² than for those with higher eGFR 1

Specific GLP-1 RAs with Evidence in CKD

First-Line Options:

1. Dulaglutide:

   • Demonstrated significantly slower GFR decline compared to insulin glargine in patients with moderate-to-severe CKD (stages G3 and G4) 1
   • No dose adjustment required in CKD, even with eGFR <30 ml/min/1.73 m² 1

2. Liraglutide:

   • Greater MACE reduction in patients with eGFR <60 ml/min/1.73 m² 1
   • No dose adjustment required in CKD 1
   • May slow progression of kidney disease 1

3. Semaglutide (injectable):

   • Proven cardiovascular benefit 1
   • No dose adjustment required in CKD 1
   • Ongoing FLOW trial specifically evaluating semaglutide for preventing ≥50% eGFR decline, kidney failure, or death due to kidney or cardiovascular causes 1

Other GLP-1 RAs with CKD evidence:

• Lixisenatide, exenatide (once weekly), albiglutide (not currently available), and efpeglenatide have also shown favorable CKD outcomes 1

Dosing and Administration in CKD

GLP-1 RA	Dosing in CKD
Dulaglutide	No dose adjustment required even with eGFR <30 ml/min/1.73 m² [1]
Liraglutide	No dose adjustment required [1]
Semaglutide	No dose adjustment required for eGFR ≥30 ml/min/1.73 m²; use with caution if eGFR <30 [2]
Exenatide	Caution when initiating or increasing dose; avoid once-weekly formulation if eGFR <30 ml/min/1.73 m² [1]
Lixisenatide	No dose adjustment required for eGFR ≥30; use not recommended if eGFR <30 ml/min/1.73 m² [1]

Adverse Effects and Monitoring

• Common side effects:

  • Nausea, vomiting, and diarrhea (occur in 15-20% of patients with moderate-to-severe CKD) 1
  • Usually tolerable with dose titration and abate over several weeks to months 1
  • Heart rate typically increases by ~5 bpm 1

• Contraindications:

  • Not recommended in patients at risk for thyroid C-cell tumors (e.g., multiple endocrine neoplasia) 1
  • Use caution in patients with history of pancreatitis 1

Clinical Application

GLP-1 receptor agonists are recommended for patients with T2D and CKD who:

1. Do not meet their individualized glycemic target with metformin and/or an SGLT2i 1
2. Are unable to use metformin and/or SGLT2i 1

Even in advanced CKD (eGFR <30 ml/min/1.73 m²), GLP-1 RAs retain glucose-lowering potency across the range of eGFR and among dialysis patients 1.

Important Considerations

• When used with insulin or insulin secretagogues, doses of these drugs may need to be reduced to avoid hypoglycemia 1
• In moderate-to-severe CKD (stages G3 and G4), rates of hypoglycemia are reduced by one-half even with concurrent insulin therapy 1
• GLP-1 RAs do not cause hypoglycemia when used alone 1
• Semaglutide is available in both injectable and oral formulations 1

GLP-1 receptor agonists represent an important therapeutic option for patients with CKD, offering benefits beyond glycemic control by potentially slowing kidney disease progression and reducing cardiovascular risk.