Baseline fasting serum c-peptide levels as a marker of oral hypoglycemic failure in type 2 diabetes in Uganda: a prospective single-arm cohort pilot study

Background: Type 2 diabetes mellitus (T2DM) is a global health challenge. Oral hypoglycemics are commonly used, but treatment failure is frequent. This study evaluated fasting serum connecting peptide (C-peptide) as a predictor of oral hypoglycemic therapy response. Methods: A prospective cohort study (Jan–Oct 2023) enrolled T2DM patients aged ≥40 with glycated hemoglobin (HbA1c) >10% despite oral therapy. Participants received metformin (2000 mg/day), glimepiride (4 mg/day), and teneligliptin (20 mg/day), plus lifestyle counseling. Fasting blood sugar (FBS) and C-peptide levels were measured at baseline. Participants were followed for 3 months, with monthly FBS and final HbA1c assessment. Results: Thirty-five participants (mean age 59.6 years; 77.1% female) were included. Most were overweight or obese, with 62.9% having hypertension and a family history of diabetes. Mean baseline C-peptide was 1.72 ng/ml and negatively correlated with 3-month HbA1c (r = -0.5383, p < 0.01). FBS declined from 10.6 mmol/L to 7.8 mmol/L (p < 0.01). The area under the receiver operating characteristic curve (AUC) for C-peptide in predicting response was 0.85, with a 1.7 ng/ml cut-off yielding 89.5% sensitivity and 81.2% specificity. Conclusion: Higher fasting serum C-peptide predicts better glycemic response to oral therapy, highlighting its potential as a clinical marker in T2DM management. Keywords: Type 2 Diabetes Mellitus; Fasting Serum C-peptide; Oral Hypoglycemic Failure; Glycemic Control