title: Comparative genotoxic and cytotoxic effects of the oral antidiabetic drugs sitagliptin, rosiglitazone, and pioglitazone in patients with type-2 diabetes: a cross-sectional, observational pilot study.
abstract: This cross-sectional, observational pilot study was designed to investigate the frequency of different endpoints of genotoxicity (sister-chromatid exchange, total chromosome aberrations, and micronucleus formation) and cytotoxicity (mitotic index, replication index, and nuclear division index) in the peripheral lymphocytes of patients with type-2 diabetes treated with different oral anti-diabetic agents for 6 months. A total of 104 patients who met the American Diabetes Association criteria for type-2 diabetes were enrolled in the study. Of the 104 patients, 33 were being treated with sitagliptin (100mg/day), 25 with pioglitazone (30mg/day), 22 with rosiglitazone (4mg/day), and 24 with medical nutrition therapy (control group). The results for all the genotoxicity endpoints were significantly different across the four study groups. Post hoc analysis revealed that the genotoxicity observed in the sitagliptin group was significantly higher than that observed in the medical nutrition therapy group, but lower than that occurring in subjects who received thiazolidinediones. All of the three cytotoxicity endpoints were significantly lower in patients treated by oral anti-diabetic agents compared with those who received medical nutrition therapy. However, the three indexes did not differ significantly in the sitagliptin, rosiglitazone, and pioglitazone groups. Taken together, these pilot data indicate that sitagliptin and thiazolidinediones may exert genotoxic and cytotoxic effects in patients with type-2 diabetes. Further investigations are necessary to clarify the possible long-term differences between oral anti-diabetic drugs in terms of genotoxicity and cytotoxicity, and how these can modulate the risk of developing diabetic complications in general and cancer in particular.
authors.affiliation: Uludag University Medical School, Department of Endocrinology and Metabolism, Bursa, Turkey. Electronic address: drozenoz@gmail.com.
authors.forename: Ozen
authors.initials: O
authors.lastname: Oz Gul
authors.forename: Nilufer
authors.initials: N
authors.lastname: Cinkilic
authors.forename: Cuma Bulent
authors.initials: CB
authors.lastname: Gul
authors.forename: Soner
authors.initials: S
authors.lastname: Cander
authors.forename: Ozgur
authors.initials: O
authors.lastname: Vatan
authors.forename: Canan
authors.initials: C
authors.lastname: Ersoy
authors.forename: Dilek
authors.initials: D
authors.lastname: Yılmaz
authors.forename: Ercan
authors.initials: E
authors.lastname: Tuncel
mesh_terms: D000368:Aged; D001786:Blood Glucose; D002869:Chromosome Aberrations / Q000187:drug effects*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D008875:Middle Aged; D010865:Pilot Projects; D000077205:Pioglitazone; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D000077154:Rosiglitazone; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011719:Pyrazines; D045162:Thiazolidinediones; D014230:Triazoles; D000077154:Rosiglitazone; D000068900:Sitagliptin Phosphate; D000077205:Pioglitazone
keywords: Cytotoxicity; Genotoxicity; Pioglitazone; Rosiglitazone; Sitagliptin; Type 2 diabetes