Patients with type 2 diabetes mellitus (T2DM) exhibit improved symptoms at the start of treatment, but their conditions subsequently deteriorate after a few months of treatment. In the present study, patients treated with glibenclamide and metformin were followed up for the evaluation of the efficacy of treatment based on some biochemical parameters in T2DM subgroups. The patients with T2DM were subgrouped according to their glycated hemoglobin (HbA1c), sex, urinary albumin to creatinine ratio (UACR), and uric acid UA levels. A total of 662 patients participated in the study, which aimed to follow up with glycated hemoglobin (HbA1c), fasting blood sugar (FBS), uric acid (UA), UACR, and lipid profiles at the beginning of treatment and after 2 and 4 months. Results showed that the best treatment effect occurred when patients were classified according to the UACR and HbA1c. In general, all parameters, especially lipid profile and UA levels, changed when patients exhibit proteinuria compared with those in normal UACR patients. Depending on the glycemic control subgroups, all parameters were higher in patients with poor glycemic control compared with those with the fair glycemic control, except for HDLc, which was lowest in the poor-control patients. The parameters revealed significant improvement (p < 0.05) in lipids, UA, UACR, and HbA1c after 2 months of treatment but subsequently remained slightly increased after 4 months of treatment. The parameters measured by using subgroups were better than those obtained from the whole group. The patients who initially experienced improved symptoms tended to ignore regular treatment and restricted diet, thereby worsening the measured parameters.