The combination of sodium-glucose transporter-2 inhibitors (SGLT2is) and metformin did not have an effect on fracture risk among patients with type 2 diabetes mellitus (T2DM). These findings, from a meta-analysis, were published in Osteoporosis International.
Publication databases were searched through December 2019 for randomized clinical trials evaluating SGLT2is and metformin dual therapy among patients with T2DM. Included studies did not include insulin use, lasted a minimum of 24 weeks, and had available data on instances of fractures. A total of 25 articles were included encompassing 19,500 patients with T2DM. The treatment groups were 9662 patients who received SGLT2is (bexagliflozin, canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, or ipragliflozin) with metformin and 9838 patients who received other active comparators (dipeptidyl peptidase 4 [DPP-4] inhibitors, glucagon-like peptide-1 [GLP-1] receptor agonists, metformin, or sulfonylurea). The mean age range of the patients was 51.6 to 60.7 years and the studies lasted from between 24 to 208 weeks.
The total instance of fracture among patients was low (0.86%). This risk was similar between the dual therapy (0.91%) and monotherapy (0.80%) groups. Of the 17 studies that included fracture location, 15.22% were hip or lumbar spine fractures and 84.78% were other. The locations of fractures did not differ between groups.
The overall risk for fracture among patients on the combination therapy compared with the monotherapy did not differ significantly (odd’s ratio [OR], 0.97; 95% CI, 0.71-1.32; I2, 0%; P =.86).
The different types of SGLT2is used among the dual therapy group had similar risk for fractures: ertugliflozin OR 0.76 (95% CI, 0.38-1.54), dapagliflozin OR 0.91 (95% CI, 0.50-1.64), empagliflozin OR 0.94 (95% CI, 0.59-1.50), and canagliflozin OR 2.19 (95% CI, 0.66-7.27).
No significant change to bone mineral density or clinically meaningful alteration in bone turnover markers were observed.
The major limitation of this study was that the underlying studies did not intend to study bone health among patients with T2DM. As such, the included studies had relatively short follow-up times (mean, 61 weeks), as bone damage is a long-term result, it remains unclear whether either treatment group would have had a response in the long-term.
The study authors concluded that metformin combined with an SGLT2is did not alter risk for fractures among patients with T2DM.
Qian B B, Chen Q, Li L, et al. Association between combined treatment with SGLT2 inhibitors and metformin for type 2 diabetes mellitus on fracture risk: a meta-analysis of randomized controlled trials. Published online August 11, 2020. Osteoporos Int. doi:10.1007/s00198-020-05590-y