Objective To identify population with type 2 diabetes mellitus (T2DM) who are more likely to benefit from switching to basal insulin (BI) treatment from premixed insulin. Methods This secondary analysis included data from a previously published study (Optimization: NCT00693771) which was a single-arm, multicenter, 16 weeks, phase IV study. The analysis included participants with T2DM inadequately controlled with premixed insulin plus oral hypoglycemic drugs (OADs) who switched to BI plus OADs. Results Among the 297 participants included for analysis, subjects with fasting C-peptide (FCP)>1.2 nmol/L group showed a trend for greater reduction in HbA1c [Least square mean difference (LSMD), -0.59; 95% confidence interval (CI), -0.98 to -0.21; p = 0.003] and FPG (LSMD, -1.36; 95% CI, -2.20 to -0.53; p = 0.002) than those with FCP <= 0.4 nmol/L. The baseline insulin glargine 100 U/mL (Gla-100) dose increased significantly in 0.4 to <= 1.2 nmol/L group with LS mean difference (SE) of 0.16 (0.01) U/kg/day (p = 0.008) compared to FCP <= 0.4 nmol/L group. When combined with Diabetes Treatment Satisfaction Questionnaire (DTSQ) score, participants with a C-peptide level of 0.4 to <= 1.2 nmol/L (OR, 4.05; 95% CI, 1.08 to 15.22; p = 0.039) had significantly higher odds of achieving HbA1c <7%. The number of participants experiencing documented symptomatic hypoglycaemia (<= 3.9 mmol/L) was higher in the FCP <= 0.4 nmol/L group compared to those in 0.4 to <= 1.2 nmol/L FCP group at any time of the day (31.6 vs. 17.1%) and during night (00:00 similar to 05:59) (17.1 vs. 7.5%). Conclusion The findings from this study proposed that FCP is an important biomarker to identify T2DM participants who experience improved glucose control without compromising on hypoglycemia levels during switch from premixed insulin to BI. Participants especially with FCP levels >1.2 nmol/L may respond better in terms of HbA1c reduction without increased hypoglycemia risk compared to those with lower FCP values.