Serum osteoglycin is stable during various glycemic challenges in healthy men.

PURPOSE: Osteoglycin is hypothesized to be metabolically active and may enhance insulin action. We hypothesized that osteoglycin levels increase during hyperglycemia as a physiological response to enhance the effects of insulin. METHODS: Eight healthy males were included in a cross-over study consisting of three study days following an 8 h fast. First, we performed an oral glucose tolerance test (OGTT); second, an isoglycemic intravenous glucose infusion (IIGI); and third, a control period consisting of a three hour fast. We analyzed blood samples for circulating osteoglycin levels during the study days. Repeated measures ANOVA was performed to compare levels of s-osteoglycin between OGTT, IIGI, and the fasting control. RESULTS: There were no differences in baseline osteoglycin levels among study days (p > 0.05). We observed no significant changes neither in absolute s-osteoglycin levels by time (p = 0.14) nor over time by study day (p = 0.99). Likewise, we observed no significant changes in percentage s-osteoglycin levels neither by time (p = 0.11) nor over time by study day (p = 0.89). CONCLUSION: We found that s-osteoglycin levels were stable for three hours during OGTT, IIGI, and fasting in healthy males. Based on the present study, circulating s-osteoglycin levels may be measured independently of fasting or non-fasting conditions. Furthermore, circulating physiological levels of glucose and insulin did not affect s-osteoglycin levels.

The risk of major osteoporotic fractures with GLP-1 receptor agonists when compared to DPP-4 inhibitors: A Danish nationwide cohort study.

Background: Type 2 diabetes mellitus (T2D) is associated with an increased fracture risk. There is little evidence for the effects of glucagon-like peptide 1 receptor agonists (GLP-1RA) on fracture risk in T2D. We aimed to investigate the risk of major osteoporotic fractures (MOF) for treatment with GLP-1RA compared to dipeptidyl peptidase 4 inhibitors (DPP-4i) as add-on therapies to metformin. Methods: We conducted a population-based cohort study using Danish national health registries. Diagnoses were obtained from discharge diagnosis codes (ICD-10 and ICD-8-system) from the Danish National Patient Registry, and all redeemed drug prescriptions were obtained from the Danish National Prescription Registry (ATC classification system). Subjects treated with metformin in combination with either GLP-1RA or DPP-4i were enrolled from 2007 to 2018. Subjects were propensity-score matched 1:1 based on age, sex, and index date. MOF were defined as hip, vertebral, humerus, or forearm fractures. A Cox proportional hazards model was utilized to estimate hazard rate ratios (HR) for MOF, and survival curves were plotted using the Kaplan-Meier estimator. In addition, Aalen's Additive Hazards model was applied to examine additive rather than relative hazard effects while allowing time-varying effects. Results: In total, 42,816 individuals treated with either combination were identified and included. After matching, 32,266 individuals were included in the main analysis (16,133 in each group). Median follow-up times were 642 days and 529 days in the GLP-1RA and DPP-4i group, respectively. We found a crude HR of 0.89 [0.76-1.05] for MOF with GLP-1RA compared to DPP-4i. In the fully adjusted model, we obtained an unaltered HR of 0.86 [0.73-1.03]. For the case of hip fracture, we found a crude HR of 0.68 [0.49-0.96] and a similar adjusted HR. Fracture risk was lower in the GLP-1RA group when examining higher daily doses of the medications, when allowing follow-up to continue after medication change, and when examining hip fractures, specifically. Additional subgroup- and sensitivity analyses yielded results similar to the main analysis. Conclusion: In our primary analysis, we did not observe a significantly different risk of MOF between treatment with GLP-1RA and DPP-4i. We conclude that GLP-1RA are safe in terms of fracture.

SGLT2 inhibitor treatment is not associated with an increased risk of osteoporotic fractures when compared to GLP-1 receptor agonists: A nationwide cohort study.

Background: Type 2 diabetes mellitus (T2D) is associated with an increased fracture risk. It is debated whether sodium-glucose cotransporter 2 (SGLT2) inhibitors influence fracture risk in T2D. We aimed to investigate the risk of major osteoporotic fractures (MOF) with SGLT2 inhibitors compared to glucagon-like peptide 1 (GLP-1) receptor agonists when used as add-on therapies to metformin. Methods: We conducted a population-based cohort study using Danish national health registries. Diagnoses were obtained from discharge diagnosis codes (ICD-10 and ICD-8-system) from the Danish National Patient Registry, and all redeemed drug prescriptions were obtained from the Danish National Prescription Registry (ATC classification system). Subjects treated with metformin in combination with either SGLT2 inhibitors or GLP-1 receptor agonists were identified and enrolled from 2012 to 2018. Subjects were then propensity-score matched 1:1 based on age, sex, and index date. Major osteoporotic fractures (MOF) were defined as hip, vertebral, humerus, or forearm fractures. A Cox proportional hazards model was utilized to estimate hazard rate ratios (HR) for MOF, and survival curves were plotted using the Kaplan-Meier estimator. Results: In total, 27,543 individuals treated with either combination were identified and included. After matching, 18,390 individuals were included in the main analysis (9,190 in each group). Median follow-up times were 355 [interquartile range (IQR) 126-780] and 372 [IQR 136-766] days in the SGLT2 inhibitor and GLP-1 receptor agonist group, respectively. We found a crude HR of 0.77 [95% CI 0.56-1.04] for MOF with SGLT2 inhibitors compared to GLP-1 receptor agonists. In the fully adjusted model, we obtained an unaltered HR of 0.77 [95% CI 0.56-1.05]. Results were similar across subgroup- and sensitivity analyses. Conclusion: These results suggest that SGLT2 inhibitors have no effect on fracture risk when compared to GLP-1 receptor agonists. This is in line with results from previous studies.