The associations of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors as add-on to metformin with fracture risk in patients with type 2 diabetes mellitus

AIM: To investigate whether sodium-glucose cotransporter-2 (SGLT2) inhibitor use as compared to dipeptidyl peptidase-4 (DPP-4) inhibitor use as add-on to metformin is associated with the risk of any fracture or major osteoporotic fractures (MOFs). METHODS: A cohort study using the Clinical Practice Research Datalink (CPRD) Aurum database was conducted. All patients aged 18 years and older with a first-ever prescription for a DPP-4 inhibitor or an SGLT2 inhibitor as add-on to metformin between January 1, 2013 and June 30, 2020 were selected. Patients starting with SGLT2 inhibitors were matched (up to 1:3) on propensity scores to patients starting with DPP-4 inhibitors. Propensity scores were calculated based on sex, age, body mass index, comorbidities, comedication and lifestyle factors. Cox proportional hazard models were used to estimate the risk of fracture with SGLT2 inhibitor use as compared to DPP-4 inhibitor use. RESULTS: A total of 13 807 SGLT2 inhibitor users (age 55.4 ± 10.6 years, 36.7% female) were included in this study, matched with 28 524 DPP-4 inhibitor users (age 55.4 ± 8.0 years, 36.4% female). The risk of any fracture with current SGLT2 inhibitor use was similar compared with current DPP-4 inhibitor use (adjusted hazard ratio [aHR] 1.09, 95% confidence interval [CI] 0.91-1.31), as was the risk of MOFs (aHR 0.89, 95% CI 0.64-1.22) and the risk of fractures at any of the individual MOF sites. Additionally, no association was found with duration of SGLT2 inhibitor use (longest duration >811 days) for any of the individual SGLT2 inhibitor agents, or after stratification by sex and age. CONCLUSION: Use of SGLT2 inhibitors was not associated with the risk of any fracture, MOFs or fracture at the individual MOF sites when compared to DPP-4 inhibitor use

The associations of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors as add-on to metformin with fracture risk in patients with type 2 diabetes mellitus

Aim: To investigate whether sodium-glucose cotransporter-2 (SGLT2) inhibitor use as compared to dipeptidyl peptidase-4 (DPP-4) inhibitor use as add-on to metformin is associated with the risk of any fracture or major osteoporotic fractures (MOFs). Methods: A cohort study using the Clinical Practice Research Datalink (CPRD) Aurum database was conducted. All patients aged 18 years and older with a first-ever prescription for a DPP-4 inhibitor or an SGLT2 inhibitor as add-on to metformin between January 1, 2013 and June 30, 2020 were selected. Patients starting with SGLT2 inhibitors were matched (up to 1:3) on propensity scores to patients starting with DPP-4 inhibitors. Propensity scores were calculated based on sex, age, body mass index, comorbidities, comedication and lifestyle factors. Cox proportional hazard models were used to estimate the risk of fracture with SGLT2 inhibitor use as compared to DPP-4 inhibitor use. Results: A total of 13 807 SGLT2 inhibitor users (age 55.4 ± 10.6 years, 36.7% female) were included in this study, matched with 28 524 DPP-4 inhibitor users (age 55.4 ± 8.0 years, 36.4% female). The risk of any fracture with current SGLT2 inhibitor use was similar compared with current DPP-4 inhibitor use (adjusted hazard ratio [aHR] 1.09, 95% confidence interval [CI] 0.91-1.31), as was the risk of MOFs (aHR 0.89, 95% CI 0.64-1.22) and the risk of fractures at any of the individual MOF sites. Additionally, no association was found with duration of SGLT2 inhibitor use (longest duration >811 days) for any of the individual SGLT2 inhibitor agents, or after stratification by sex and age. Conclusion: Use of SGLT2 inhibitors was not associated with the risk of any fracture, MOFs or fracture at the individual MOF sites when compared to DPP-4 inhibitor use

Prevalent Morphometrically Assessed Vertebral Fractures in Individuals With Type 2 Diabetes, Prediabetes and Normal Glucose Metabolism:The Maastricht Study

BACKGROUND: Type 2 diabetes (T2D) is frequently reported to be associated with an increased fracture risk. Epidemiological data on prevalent morphometric vertebral fractures (VFs) in T2D are sparse and even less is known in the prediabetic state. PURPOSE: To determine the association between prevalence and severity of morphometric VFs and glucose metabolism state: normal glucose metabolism (NGM), impaired glucose metabolism (prediabetes) or T2D. METHODS: This study included cross-sectional data from 3625 participants of the Maastricht Study who had a vertebral fracture assessment on lateral Dual Energy X-Ray Absorptiometry images. VFs were classified based on morphometric assessment into mild, moderate and severe VFs (respectively 20–24%, 25–39% or ≥40% reduction in expected vertebral body height). Logistic regression models were used to investigate the association between glucose metabolism status and the prevalence and severity of VFs. Analyses were adjusted for subject characteristics and life-style factors. RESULTS: T2D individuals were older (62.8 ± 7.5 years old) and less often female (30.5%) compared to the NGM group (57.7 ± 8.5 years old, and 58.8% female, respectively). At least one mild, moderate or severe prevalent VF was found in 8.6% of the men and 2.2% of the women in the T2D group, in 9.4% and 8.4% in the prediabetes group and in 9.1% and 4.8% in the NGM group, respectively. After adjustment T2D in women was associated with a lower probability of having a prevalent VF compared to NGM [adjusted OR 0.25 (95% CI 0.09-0.65)], while this was not the case for prediabetes. Furthermore, women with T2D had a significantly lower probability of a prevalent moderate or severe VF [adjusted OR 0.32 (95% CI 0.11-0.96)]. In men there was no significant association between T2D or prediabetes and prevalent VFs. CONCLUSION: Women with T2D had a lower probability of prevalent VFs compared to women with a normal glucose metabolism, while this was not the case for men with T2D and participants with prediabetes