To determine the effects of SGLT2 inhibitors on bone turnover markers in patients of type 2 Diabetes Mellitus

Abstract

Background and Objectives: Type 2 Diabetes Mellitus (T2DM) is known to cause microvascular and macrovascular complications, placing a burden on healthcare, with pathophysiology encompassing β-cell dysfunction, insulin resistance, and inflammation. Bone remodelling which provides essential elements of skeletal stability and elasticity is defined by the regulation of adult bone mass and maintenance. Skeletal fragility in diabetes relates to obesity, high blood glucose, oxidative stress, and advanced glycation end products. Long-term exposure to a diabetic environment subtly alters bone remodelling, as suggested by osteoblastic and osteoclastic bone biomarkers in studies. Certain anti-diabetic drugs like pioglitazone, rosiglitazone, and thiazolidinediones may cause bone loss, while metformin and sulfonylureas have neutral or positive effects. Group of SGLT2 inhibitors, may have variable effects on bone biomarkers, e.g. canagliflozin raise concerns related to skeletal structure integrity, but dapagliflozin and empagliflozin haven’t show an increased risk of fracture. Therefore, the present study was designed to assess the effect of frequently prescribed SGLT2 inhibitors e.g. dapagliflozin and empagliflozin on bone biomarkers.
Methods: The observational, prospective, open- label study was conducted on 40 newly diagnosed T2DM patients (40-60 years) in Northern India with follow-up of 24 weeks. Those with suboptimal glycemic control were prescribed SGLT2 inhibitors in addition to their existing treatment. Anthropometric measurements, including height, waist circumference, and BMI, were taken at baseline and after 6 months. Blood pressure was recorded using a mercury sphygmomanometer. Biochemical parameters such as fasting/postprandial glucose, HbA1c, serum phosphorus, calcium, vitamin D, parathormone, and various bone markers were analyzed from venous blood samples. Data was analyzed with Microsoft Excel and Prism GraphPad 9.
Interpretation & Conclusion: The 24-week study suggests SGLT2 inhibitor use increases bone resorption markers e.g., FGF23 and parathormone, potentially raising osteoporotic risk. Bone formation markers e.g., BALP and Osteocalcin remain unchanged. Further research on long-term effects of SGLT2 inhibitors is needed. A cautious approach, especially for those with bone health concerns, is recommended when considering antidiabetic drugs.
Results: Statistical analysis showed significant changes (p<0.05%). SGLT2 inhibitors prescribed in T2DM patients have shown significant increase in serum FGF-23 levels, suggesting its potential role as a biomarker for adverse cardiovascular events, secondary impact on bone metabolism and increased risk of fractures. The other bone biomarkers sclerostin and osteocalcin show insignificant changes in serum values over a six month follow up period, while bone-specific markers like BALP remain unaffected, suggesting potential complexities in bone metabolism influenced by weight loss and diabetes-related factors.