Objective: To compare the therapeutic effects of alendronate sodium and calycid D combined with metformin on type 2 diabetes mellitus (T2DM) with osteoporosis. Methods: A total of 109 patients with T2DM with osteoporosis who were admitted to our hospital from April 2016 to January 2019 were selected. According to the random number table, the patients were divided into two groups: calycid group D (n=54, calycid D) and alendronate sodium group (n=55, alendronate sodium). The clinical effect, blood glucose index, bone metabolism index, lumbar L2 ~ L4 and femoral neck bone mineral density of the two groups were compared. Results: The total effective rate of alendronate sodium group was 83.64% (46/55), which was higher than 62.96% (34/54) in calycid group D (P<0.05). The bone mineral density of L2-L4 and femoral neck of the two groups increased at 1 month after treatment, and those of alendronate sodium group was higher than that of calycid group D (P<0.05). 1 month after treatment, the level of bone gla protein (BGP) increased in both groups, and that of alendronate sodium group was higher than that of calycid group D (P<0.05). While the level of type I collagen cross-linked C-terminal peptide (s-CTX), bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase-5b (TRAP-5b) were decreased, and those of alendronate sodium group were lower than those of calycid group D (P<0.05). The fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) of the two groups decreased at 1 month after treatment, and those of alendronate sodium group were lower than those of calycid group D (P<0.05), but there was no difference between the two groups at 1 month after treatment (P>0. 05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: Compared with the treatment of calycid D combined with metformin, alendronate sodium combined with metformin has a significant effect on T2DM patients with osteoporosis, which can effectively improve bone metabolism and bone mineral density, and it does not affect the effect of hypoglycemic, which has a certain clinical application value. [ABSTRACT FROM AUTHOR]