GLP-1 drugs in CKD: an endocrinologist's guide to starting low and staying on

What it covers

GLP-1 receptor agonists and the dual incretin drugs add kidney and cardiometabolic benefit on top of SGLT2 inhibitors in type 2 diabetes with CKD. Yet many patients never get them. Clinicians worry about nausea, dehydration and acute kidney injury, and the dosing steps are fiddly. In this CJASN "How I Treat" case, UCLA endocrinologist Dianne Cheung argues the problem is execution, not evidence.

Key points

• The case: a 71-year-old man with type 2 diabetes, obesity, hypertension and stage 3 CKD (eGFR 51). He moved from liraglutide to semaglutide and later to tirzepatide. From January 2021 to 2025 he lost 28 lb, about 10%. He needed roughly 35% less basal insulin and 65% less prandial insulin. His albuminuria fell while he stayed on therapy and rose during gaps.
• AKI fears are overstated, she argues. In a network meta-analysis of 18 outcome trials (156,690 people, 2,051 AKI events), GLP-1 receptor agonists had a neutral effect on AKI. A Cochrane review in CKD with diabetes found no clear increase.
• Her routine: start at the lowest dose and titrate slowly. Recheck creatinine and electrolytes within 2 to 4 weeks of starting or a big dose step in higher-risk patients, sooner if intake drops. Judge kidney response by albuminuria at 3 to 6 months. A small early eGFR dip should not prompt reflex stopping if volume is stable and other causes of AKI are excluded.
• Prevent hypoglycemia. In tightly controlled patients she cuts basal and prandial insulin by about 10% to 20% at the start, and prandial often needs more. She also trims sulfonylureas and uses glucose monitoring.
• Protect muscle. Older or frail patients need enough protein and calories, a renal dietitian, and resistance training two to three times a week.
• Give sick-day rules. Persistent vomiting, diarrhea, poor intake, dizziness or low urine output should prompt a call to the care team. Poor intake or suspected AKI means pausing escalation or holding the drug.

Why it matters

This is a usable checklist for nephrologists. Its central lesson is that continuity counts. In this patient, eGFR was steadier on continuous therapy and dipped during interruptions.

Caveats

It describes one patient, and the link between continuity and kidney markers is observational within that single case. The figure's values are not given in the text. Most trials excluded advanced CKD and people without diabetes, so the author urges caution there. The 10% to 20% insulin cut reflects her practice and one pharmacy study, not trial evidence.

Industry ties: the author reports clinical trial research funding from Lilly and Corcept.

The source: Cheung DS. GLP-1 Receptor Agonists in CKD: A Case-Based Discussion of Translating Evidence into Practice. Clin J Am Soc Nephrol. Published online ahead of print 2026. doi:10.2215/CJN.0000001252 Read the original

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