C-Peptide Testing in SGLT2 Inhibitor Initiation

Introduction to SGLT2 Inhibitor Therapy

The American College of Cardiology recommends against routine C-peptide measurement before initiating SGLT2 inhibitors to prevent euglycemic ketoacidosis, instead emphasizing clinical risk assessment and patient education 1, 2, 3, 4.

Patients with Type 2 diabetes requiring insulin are at particular risk for euglycemic ketoacidosis, and key clinical factors to assess include history of diabetic ketoacidosis, insulin-requiring diabetes, and recent insulin dose reductions or discontinuation 1, 2, 3, 4.
The American Diabetes Association and KDIGO consensus reports highlight the importance of identifying clinical risk factors rather than laboratory markers of endogenous insulin production 3, 5.

The American College of Cardiology and Kidney International recommend maintaining at least low-dose insulin in insulin-requiring individuals when starting SGLT2 inhibitors to mitigate euglycemic ketoacidosis risk 3, 4.
Patient education regarding symptoms of diabetic ketoacidosis and the importance of seeking urgent medical attention is critical, as patients must understand to seek help if symptoms develop 2, 7, 4.
Instituting a sick day protocol that includes instructions to pause SGLT2 inhibitors during periods of acute illness, reduced oral intake, vomiting, or dehydration is essential 3, 4, 6.

Providing blood or urine ketone monitoring supplies and educating patients to check ketones when feeling unwell is recommended, with blood β-hydroxybutyrate measurement being more accurate than urine ketones 3, 4, 6.
If HbA1c is well-controlled at baseline or there is a history of frequent hypoglycemic events, consider reducing total daily insulin dose by approximately 20% when starting SGLT2 inhibitor therapy, but never discontinue insulin entirely 2, 7, 3, 4.

The American College of Cardiology guidelines list history of diabetic ketoacidosis as a consideration for alternative agents 1, 2.
For patients with ketonuria at baseline, address the underlying cause of ketosis before considering an SGLT2 inhibitor, and alternative glucose-lowering agents that don't increase ketone production should be used in patients at very high risk for ketoacidosis 6.

No guideline recommends routine C-peptide measurement before SGLT2 inhibitor initiation, and the evidence-based approach prioritizes clinical assessment, patient education, sick day protocols, ketone monitoring supplies, and maintaining adequate insulin therapy over laboratory screening with C-peptide 1, 2, 3, 5, 8.