Do some anti-diabetic medications affect the risk of fractures in patients with type 2 diabetes?

This analysis investigated the relationship between anti-diabetic medications and the risk of fractures in patients with type 2 diabetes (T2D). The data showed that glucagon-like peptide-1 receptor agonists (GLP1-RAs) and sulfonylurea (SU) provided better protection against fractures compared to thiazolidinedione (TZD) or dipeptidyl peptidase-4 inhibitors (DPP-4is) while sodium-glucose cotransporter-2 inhibitors (SGLT-2i) increased the risk of fractures compared to GLP1-RAs.

Patients with T2D are predisposed to developing fractures (broken bones). Bone collagen integrity is affected by advanced glycation end products (AGEs). AGEs are formed when proteins or fats combine with sugars in the bloodstream. This alters bone collagen resulting in fragile bones and increases the risk of osteoporosis (reduced bone mineral density; BMD) and fractures. Osteoporotic fractures lead to pain and disabilities.

Patients with T2D are commonly treated with anti-diabetic medications. These may include GLP-1RAs like exenatide (Byetta) and liraglutide (Victoza), SUs such as glimepiride (Amaryl), thiazolidinediones like pioglitazone (Actos) and rosiglitazone (Avandia), DPP-4is, such as saxagliptin (Onglyza) and SGLT2is like canagliflozin (invokana). However, it remains unclear whether anti-diabetic medications contribute to the risk of fractures in patients with T2D.

This study analyzed the results of 161 published articles that included 191,361 patients with T2D. Patients had a total of 2,916 fractures. The published articles compared seven classes of anti-diabetic medications to a placebo. Patients were evaluated to determine if there was a link between medication class and fracture occurrence. Patients were followed for at least 24 weeks.

Patients treated with GLP1-RAs had a significantly lower risk of fracture compared to placebo (by 30%). There was a significant increase in the risk of fracture with saxagliptin (by 2.4 times), rosiglitazone (by 2.4 times), and canagliflozin (by 1.3 times).

Liraglutide significantly decreased fracture risk by 40%. GLP1-RA (by 50%) and SU (by 46%) provided greater protection against fractures compared to TZD.

DPP-4i (by 76%), SGLT2i (by 50%), and placebo (by 44%) were associated with a higher fracture risk compared to GLP1-RA. There was an increased fracture risk with the use of DPP-4i compared to SU (by 55%). TZD was most likely to result in fractures.

The study concluded that differences were seen in the relationship between classes of anti-diabetic medications and fracture risk in patients with T2D.

The study analyzed the results of other studies that did not define fracture in the same manner. Other important risk factors were not addressed such as bone mineral density and simultaneous use of other medications.