Introduction: Abnormalities of glucose metabolism that occur in diabetic patients describe an increased risk in the development and prognosis of certain cancers. Metformin is a first-line therapy for patients with type 2 diabetes melitus has been associated with a reduced risk of various cancer cells. This study compares and analyzes the effectiveness of treatment in group of metformin/combination and non-metformin towards anti-p53 antibody ​​and their relation to HbA1c in type 2 diabetes mellitus patients who have risk factors for cancer. Subjects and Methods: We conducted an observational study using cross-sectional design with inclusion of 32 people in Puskesmas Pasar Minggu, Puskesmas Cimanggis, RSUD Depok, and volunteers patient in Tangerang district using total sampling technique. Anti-p53 antibody was measured using ELISA kit for anti-p53 Test whereas HbA1c was  measured in an accredited clinical lab by ion exchange HPLC method. Results: The average of anti-p53 antibody were 0.17 ± 0.07  in metformin/combination group and 0.25 ± 0.12 in non-metformin group. However, there was no statistical significant difference between the group of metformin/combination and non-metformin (p=0.970). On the other hand, there was a strongly negative correlation between HbA1c values and anti-p53 antibody ​​in group of non-metformin (r =-0.709; p=0.003) but none in the metformin single dose or combinations group (r = -0.056; p = 0.830). Conclusion: Anti-p53 antibody did not have a significant difference neither in metformin/combination group nor in non-metformin group. On the contrary, anti-p53 antibody seems to be negatively associated with HbA1c in the group of non-metformin but none in metformin or combinations group.