Presentation (CTI)

OBJECTIVES: DMTs like teplizumab use C-peptide preservation as a primary endpoint. However, health economic models require robust clinical outcome relationships for cost-effectiveness assessment. We systematically reviewed evidence linking C-peptide levels to clinical outcomes, healthcare resource utilization (HCRU) and quality-of-life outcomes to inform economic modelling parameters for T1D interventions.
METHODS: A systematic literature review was conducted following Cochrane guidelines, searching MEDLINE and Embase (inception-May 2025) to identify studies reporting C-peptide-related clinical outcomes in T1D patients. Included studies underwent critical appraisal, requiring documented diabetes duration and C-peptide assessment methodology. C-peptide assessment methods varied (random, fasting, or stimulated) across studies. Extracted economic modelling relevant outcomes included severe hypoglycemia, diabetic ketoacidosis (DKA), microvascular complications, insulin requirements, and glycaemic control metrics. Cost-driving thresholds were identified.
RESULTS: From 10,747 abstracts, 117 studies provided economic modelling inputs. Higher C-peptide levels (≥0.2 vs <0.2 nmol/L) were consistently associated with cost-relevant clinical benefits. Severe hypoglycemia and DKA incidence showed substantial reductions in patients with preserved C-peptide. Daily insulin dose requirements demonstrated inverse relationships with C-peptide and preserved β-cell function. Long-term complications: retinopathy progression, nephropathy development, and neuropathy prevalence were lower in patients with higher C-peptide. Time-in-range improvements were consistently reported with detectable C-peptide (≥0.02 nmol/L), correlating with reduced glucose monitoring requirements. Pooled estimates were not feasible due to methodological heterogeneity; however, threshold analysis identified ≥0.2 nmol/L as associated with major clinical benefits, with intermediate benefits at 0.02-0.2 nmol/L. HCRU (emergency department visits and specialist referrals) showed inverse relationships with C-peptide preservation.
CONCLUSIONS: C-peptide preservation demonstrates quantifiable relationships with cost-driving clinical outcomes, supporting its validity as a surrogate endpoint. Identified thresholds (major benefits: ≥0.2 nmol/L, intermediate benefits: ≥0.02 nmol/L) provide robust parameters for cost-effectiveness analyses of DMTs, enabling evidence-based economic evaluation of β-cell preservation interventions and facilitating health technology assessment submissions and reimbursement decisions for emerging T1D treatments.