Table 2.

General characteristics of animal studies assessing the effect of MF on osseointegration of implants.

Author	Year	Animal model	Number of participants	Study groups and intervention	Implant site	Dose of metformin	Study duration	Outcomes
Inouye et al.79	2014	Wistar-Kyoto rats Goto-Kakizaki DM rats	EG I = 12 EG II = 12 CG = 12	EG I = DM + MF EG II = DM CG = non-DM (no treatment)	Right maxillary molars	100 mg/kg/day	4 weeks	No significant effect of MF was observed on bone-implant contact and trabecular volume in diabetic rats. MF improved bone volume in diabetic rats.
Serrão et al.80	2017	Diabetic rats	EG I = 10 EG II = 10 CG = 10	EG I = DM EG II = DM + MF CG = non-DM (no treatment)	Tibia	100 mg/kg/day	30 days	MF had no significant effect on bone-implant contact and bone area. Increased OPG+ cells and a decreased RANKL/OPG ratio were observed.
Bastos et al.81	2017	Wistar rats	EG = 10 CG = 10	EG = MF CG = no treatment	Tibia	40 mg/kg/day	30 days	MF decreased bone-implant contact and bone area. The number of RANKL+ cells increased.
Lin et al. 82	2020	Sprague Dawley rats	EG I = 10 EG II = 10 EG III = 10 CG = NS	EG I = sham surgery (n = 10) EG II = OVX + MF EG III = OVX only CG = NS	Right maxillary molars	20 mg/ml/day	14 days	MF enhanced osseointegration and bone formation in rat models of induced osteoporosis.
Yıldırım et al.83	2020	Sprague Dawley rats	EG = 10 CG = 10	EG = MF CG = no treatment	Tibia	40 mg/kg/day	28 days	MF induced elevated peri-implant bone fill ratios.
Sun et al.84	2021	Wistar rats	EG I = 06 EG II = 06 CG = 06	EG I = MF-50 EG II = MF-100 CG = no treatment	Femur	MF-50: 50 mg/kg/day MF-100: 100 mg/kg/day	4 weeks	MF increased bone-implant contact. At doses of 100 mg/kg/day MF had a greater effect on bone-implant contact than 50 mg/kg/day.

TP, total participants; EG, experimental group; CG, control group; MF, metformin; NS, not specified; OVX, ovariectomy.