Objective To observe the effects of different doses of metformin combined with insulin and insulin alone on bone metabolism-related biochemical parameters in patients with type 1 diabetes mellitus, and to explore the effect of metformin on bone metabolism. Methods In this retrospective study, 128 adult patients with type 1 diabetes mellitus were assigned to observation group or control group according to the treatment methods. Among them, 67 patients in the observation group were treated with metformin combined with insulin to control blood glucose, while 61 patients in the control group were treated with insulin alone. Blood glucose, glycosylated hemoglobin, 25-hydroxyvitamin D (25(OH)D), bone specific alkaline phosphatase (BALP), N-terminal mid-fragment of osteocalcin (N-MID OC), serum calcium, serum phosphorus, urinary calcium to creatinine ratio and lumbar vertebra bone mineral density (BMD) were collected before and after treatment for 72 weeks in the 2 groups to analyze the effect of metformin combined with insulin on bone metabolism. According to the dose of metformin, the patients in the observation group were divided into low-dose (0.5 g/d) group (n=20), medium-dose (1.0 g/d) group (n=23) and high-dose (1.5 g/d) group (n=24). The effects of different doses of metformin on bone metabolism parameters of patients were analyzed. Results Before treatment, there were no significant differences in blood glucose, glycosylated hemoglobin or bone metabolism-related parameters between the observation group and the control group (all P>0.05). After 72 weeks of treatment, blood glucose and glycosylated hemoglobin in the 2 groups were significantly lower than those before treatment (all P<0.05), but there was no significant difference between the 2 groups (both P>0.05). After treatment, BALP, N-MID OC and lumbar vertebra BMD in the observation group were higher than those before treatment and those after treatment in the control group (all P<0.05), while 25(OH)D, serum calcium, serum phosphorus and urinary calcium to creatinine ratio had no significant differences compared with those before treatment or those in the control group (all P>0.05). In the control group, there were no significant differences in lumbar vertebra BMD or bone metabolism-related parameters before and after treatment (all P>0.05). In the observation group, BALP and N-MID OC in the high-dose group were significantly higher than those in the medium-dose group and low-dose group after treatment (all P<0.01). Multiple linear regression analysis showed that metformin dose was positively correlated with BALP (β=0.266, P=0.035) and N-MID OC (β=0.355, P=0.008), and negatively correlated with urinary calcium to creatinine ratio (β=-0.296, P=0.026). Conclusion Metformin used for controling glucose in patients with type 1 diabetes mellitus has a protective effect on bone tissue, and may inhibit the occurrence of osteoporosis.