Type 2 Diabetes Treatments and Bone Fracture Risks
Diabetes is becoming a global public health issue, with over 422 million individuals diagnosed worldwide.1 Those with type 2 diabetes (T2D) produce insufficient insulin, often due to obesity or diet, with treatments generally based around weight loss or managing insulin production. If left unchecked, T2D can lead to cardiac issues, kidney failure, blindness, and other complications. Typical treatments include thiazolidinediones, to target insulin resistance, human insulin, to supplement insulin, and Glucagon-like peptide-1 (GLP-1) analogs which are GLP-1 receptor agonists, to promote glycemic control.2,3 Unfortunately, a higher risk of bone fractures has been identified in those with T2D as well. A team, led by Wei-Ren Shen of the Tohoku University of Japan, has looked at the correlation between T2D treatments and bone fractures, as reported in the Journal of Immunology Research. The researchers noted that while thiazolidinedione and insulin treatments are linked to increased bone fracture risk, treatment with metformin is associated with decreased bone fracture risk. They noted that mice deficient in GLP-1 receptors had increased osteoclast formation, suggesting that GLP-1 signaling plays a role in inhibiting bone reabsorption and promoting bone formation. Exendin-4, or exenatide, is a GLP-1 receptor agonist that is resistant to cleavage by dipeptidyl peptidase IV (DPP-IV), with extended half-life and increased potency. It has been approved and successfully used for T2D treatment for over 10 years. The team injected mice with either lipopolysaccharide (LPS), which induces inflammation and bone loss, a mixture of LPS and exendin-4, exendin-4 alone, or a placebo. They found that there were fewer LPS-induced osteoclasts in the two groups that had received exendin-4. Furthermore, there was evidence of lowered bone destruction in the two groups.4 Exendin-4 is a good treatment for T2D, while at the same time preventing bone fractures.
- W. Shen, et al., Journal of Immunology Research, 18, 1 (2018). doi:10.1155/2018/5783639