TABLE 3.

Clinical usefulness of the assessment of plasma C‐peptide levels in people with diabetes

Setting	Potential clinical role	Areas of uncertainties
Uncertain diagnosis in long‐standing insulin‐treated diabetes	To recognize type 1 diabetes some years after onset, when autoantibody measurement may result in false negative	C‐peptide values 0.20‐0.60 nmol/L are not discriminatory Correct timings of first C‐peptide measurement and of subsequent retesting are still arbitrary
Type 1 diabetes	During preclinical phase, to assess the risk and rapidity of progression towards diabetes onset During the honeymoon period, to assess the rate of beta‐cell function decline, for a prompt intervention when absolute insulin deficiency occurs To confirm insulin deficiency in patients without a definite type 1 diabetes phenotype	Lack of standardization of C‐peptide measurement
Type 2 diabetes	To identify subgroups of people with type 2 diabetes within the severe insulin‐deficient cluster To predict the response to treatment with basal insulin and the related hypoglycaemia risk To individualize people on insulin therapy less probable to respond to a GLP‐1 RA	C‐peptide as a marker of beta‐cell competence is affected by the presence of insulin resistance Often overestimates beta‐cell competence because of concomitant hyperglycaemia C‐peptide levels could theoretically be affected by ongoing antidiabetes therapies Whether C‐peptide may help in identifying patients requiring insulin therapy and those who may safely withdraw from ongoing insulin therapy is yet to be proven A role for C‐peptide in assessing the risk of euglycaemic ketoacidosis in candidates for SGLT2 inhibitor therapy has to be proven
Adult‐onset autoimmune diabetes not on insulin therapy	To predict disease progression To guide the decision about the right timing to start insulin therapy and use of different glucose‐lowering agents	Suggested C‐peptide cut‐offs are in part arbitrary because of the graded effect of C‐peptide Insulin resistance if often present in adult‐onset autoimmune diabetes, affecting the value of C‐peptide as a marker of beta‐cell competence
Diabetes complications	To aid hypoglycaemia and complications risk stratification	Lack of definitive data showing direct tissue effects

Abbreviations: GLP‐1 RA, glucagon‐like peptide‐1 receptor agonist; SGLT2, sodium‐glucose co‐transporter‐2.