If a patient with type 2 diabetes and a normal estimated Glomerular Filtration Rate (eGFR) of 60, experiences a significant decline in eGFR to 23 after starting a Glucagon-like peptide-1 (GLP-1) receptor agonist, should the medication be stopped?

Immediate Action Required: Stop the GLP-1 Receptor Agonist and Investigate the Cause

You should immediately discontinue the GLP-1 receptor agonist and urgently investigate the cause of this precipitous eGFR decline from 60 to 23 mL/min/1.73 m², as this represents acute kidney injury rather than the expected hemodynamic changes associated with GLP-1 therapy. 1

Why This is NOT an Expected GLP-1 Effect

Expected vs. Observed Changes

• SGLT2 inhibitors cause an initial, reversible eGFR decline of 3-5 mL/min/1.73 m², which is hemodynamic and generally not an indication to discontinue therapy 1
• GLP-1 receptor agonists do NOT cause significant acute eGFR declines - they are actually renoprotective and slow eGFR decline over time 2, 3, 4
• A drop from 60 to 23 mL/min/1.73 m² represents a 62% decline in kidney function, which is pathological and requires immediate investigation 1

This Represents Acute Kidney Injury

• The magnitude of decline (37 mL/min/1.73 m²) far exceeds any expected medication effect 1
• GLP-1 receptor agonists reduce composite kidney outcomes by 18-21% and slow eGFR decline, they do not cause acute drops 2, 3
• This patient has progressed from CKD stage 2 (eGFR 60) to CKD stage 4 (eGFR 23), which demands urgent evaluation 1

Urgent Differential Diagnosis to Investigate

Volume Depletion (Most Likely Culprit)

• GLP-1 receptor agonists cause gastrointestinal side effects in 15-20% of patients with moderate-to-severe CKD, including nausea, vomiting, and diarrhea 2
• Severe gastrointestinal reactions can lead to volume depletion and prerenal acute kidney injury 2
• Assess for signs of dehydration, orthostatic hypotension, and recent fluid losses 1

Concurrent Nephrotoxic Exposures

• Review all medications for NSAIDs, ACE inhibitors/ARBs (especially if recently initiated or dose-increased), diuretics, or other nephrotoxins 1
• Evaluate for contrast exposure, antibiotics, or other acute insults 1

Intrinsic Kidney Disease Progression

• This magnitude of decline suggests an acute process rather than chronic progression 1
• Consider urinalysis, urine protein-to-creatinine ratio, and renal ultrasound 1

Management Algorithm

Immediate Steps (Within 24-48 Hours)

1. Stop the GLP-1 receptor agonist immediately 2
2. Assess volume status - check orthostatic vital signs, mucous membranes, skin turgor 1
3. Review all medications - hold ACE inhibitors/ARBs, NSAIDs, and diuretics temporarily 1
4. Order urgent labs: repeat creatinine, BUN, electrolytes, urinalysis, urine protein-to-creatinine ratio 1
5. Ensure adequate hydration - IV fluids if volume depleted 1

Follow-Up (Within 1 Week)

• Recheck eGFR after volume repletion and medication adjustments 1
• If eGFR does not improve significantly, consider nephrology referral for possible biopsy 1
• Evaluate for other causes of acute kidney injury 1

When to Restart GLP-1 Therapy (If Appropriate)

Only After Full Recovery and Investigation

• GLP-1 receptor agonists can be safely used with eGFR as low as 15 mL/min/1.73 m² for most agents (dulaglutide, liraglutide, semaglutide) 1, 2
• If the acute kidney injury was due to volume depletion from GI side effects, consider restarting at a lower dose with slower titration once eGFR recovers 1, 2
• Monitor eGFR closely when reinitiating, especially if severe gastrointestinal reactions develop 2

Preferred Agents for Reduced Kidney Function

• Dulaglutide, liraglutide, and semaglutide require no dose adjustment and can be used with eGFR >15 mL/min/1.73 m² 1, 2
• Exenatide requires caution with eGFR 30-50 mL/min/1.73 m² and is not recommended with eGFR <30 1, 2

Critical Pitfall to Avoid

Do not confuse this acute, severe eGFR decline with the expected, mild, reversible hemodynamic changes seen with SGLT2 inhibitors. 1 GLP-1 receptor agonists do not cause this pattern of kidney function decline - this represents acute kidney injury requiring immediate investigation and management. 2, 3, 4