Canagliflozin and dapagliflozin are sodium-glucose cotransporter 2 (SGLT2) inhibitors. SGLT2 is the membrane protein in the kidney which is responsible for reabsorption of glucose. The capability of inhibiting these proteins has proven to effectively control blood sugar, cholesterol, and triglycerides. This type of compound has become the go-to method in the treatment of type 2 diabetes. However, there are also concerns about possible unfavorable side-effects that must be addressed.
A recent study at the Medical University of Silesia looked into the effects that canagliflozin and dapagliflozin may have on bones. The experiment used Wistar rats and induced type 2 diabetes by use of high-fat diet followed by an injection of streptozocin. The chemicals were then administered to the animals once a day by oral gavage for a total of 4 weeks of treatment. During this time, the blood glucose and grip strength were measured weekly. 4 weeks of treatment in the life of a rat is comparable to approximately 2.5 years for a human.
At the end of the treatment, the animals were sacrificed, and the organs, bones, and blood serum were collected and analyzed. Biochemical concentrations in the serum were measured, as well as mechanical properties and mineral composition of the bones.
The results showed that both canagliflozin and dapagliflozin effectively normalized several biochemical metabolic parameters in this diabetic model. However, they were found to also unfavorably affect the skeletal system. Moreover, these SGLT2 inhibitors were not equivalent in regards to their impact on bones. Therefore, each SGLT2 inhibitor ought to be individually assessed for its impact on the skeletal system. In a situation involving both diabetes and high risk of bone fracture, the choice of SGLT2 inhibitor presents a serious concern. Further evaluation of these inhibitors should be continued.
Londzin P, Zych M, Janas A, et al. Effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, dapagliflozin and canagliflozin, on the musculoskeletal system in an experimental model of diabetes induced by high-fat diet and streptozocin in rats. Biomed Pharmacother. 2025 Mar:184:117912. PMID: 39955854