Table 2.

Effects of metformin on thyroid cancer as reported in clinical studies.

Reference	Study Design	Objective	Patients Characteristics	Metformin Dose	Duration of Treatment or Follow Up	Conclusions
Tseng et al. [42]	Clinical observational trial	To investigate the association between metformin use and thyroid cancer risk.	795,321 metformin users and 619,402 non-metformin users, Taiwanese patients with T2D.	Cumulative dose of 263,000 mg.	9 months	Metformin decreased thyroid cancer risk by 32%.
Cho et al. [46]	Retrospective cohort study	To investigate the association between metformin and thyroid cancer development.	Korean population: 128,453 metformin users and 128,453 non-users.	Mean cumulative dose of 868,169 (±563,221) mg.	1633 (±915) days	Metformin reduced risk cancer by 31%.
Klubo-Gwiezdzinska et al. [47]	Single-center observational study	Whether the efficacy of conventional treatment of DTC is affected by therapy with metformin in patients with diabetes.	Patients with diabetes treated (n = 34) or not (n = 21) with metformin and control patients without diabetes (185).	500–2000 mg/day.	4.4 (±3) years	Age, locoregional metastases, distant metastases, and lack of treatment with metformin were associated with increased risk for shortened progression-free survival. Metformin-treated individuals had smaller tumor size and better remission rates.
Jang et al. [48]	Retrospective study	To evaluate the clinical outcome of patients with diabetes and DTC according to metformin treatment.	60 patients with diabetes and 201 control patients with DTC after total thyroidectomy.	Mean dose of 979 mg.	7.4 (±4.8) years	Metformin treatment was associated with longer disease-free survival.

T2D: Type 2 Diabetes Mellitus, IR: Insulin resistance, DTC: Differentiated Thyroid Cancer.