John-Michael Gamble1, Jennifer R Donnan2, Eugene Chibrikov2, Laurie K Twells3, William K Midodzi4, Sumit R Majumdar5. 1. School of Pharmacy, University of Waterloo, Kitchener, Ontario, Canada; School of Pharmacy, Memorial University, St. John's, Newfoundland and Labrador, Canada. Electronic address: jm.gamble@uwaterloo.ca. 2. School of Pharmacy, Memorial University, St. John's, Newfoundland and Labrador, Canada. 3. School of Pharmacy, Memorial University, St. John's, Newfoundland and Labrador, Canada; Faculty of Medicine, Memorial University, St. John's, Newfoundland and Labrador, Canada. 4. Faculty of Medicine, Memorial University, St. John's, Newfoundland and Labrador, Canada. 5. Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Abstract
AIMS: Mixed evidence exists for the effect of incretin-based therapies on osteoporosis in type-2 diabetes. Therefore, we conducted a cohort study to determine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and common osteoporotic "fragility fractures" (upper extremity, hip, spine). METHODS: The UK-based Clinical Practice Research Datalink was used to identify adults without prior fractures receiving a new anti-diabetic drug or a new type-2 diabetes diagnosis between 2007 and 2016. The primary aim was to compare new-users of DPP-4 inhibitors versus new-users of sulfonylureas (SU). The association between DPP-4 inhibitors and incident fractures was estimated using Cox proportional hazards models. Deciles of high-dimensional propensity scores and other anti-diabetic drugs were used as covariates. RESULTS: We identified 7993 and 26,636 new-users of DPP-4 inhibitors and SUs, respectively. At cohort entry, the mean age was 58.8, 40% were female, mean diabetes duration was 1.3 years, and 42% had A1c > 9%. Over 9 years (mean follow-up = 1.2 years), the incident rate of fragility fractures was lower among DPP-4 versus SU users (3.0/1000 vs. 5.2/1000 person-years; P-value = 0.007). After adjustment, there was no statistically significant difference in fracture risk (hazard ratio adjusted, aHR = 0.80, 95%CI 0.51-1.24; P-value = 0.3125). In a secondary analysis, DPP-4 inhibitors were not associated with a difference in fracture risk compared to insulin (aHR = 0.91, 95%CI 0.40-2.09); however were associated with a lower fracture risk versus thiazolidinediones (aHR = 0.47, 95%CI 0.26-0.83). Sensitivity analyses supported findings. CONCLUSIONS: DPP-4 inhibitors are not associated with an increased risk of fragility fractures compared with SUs or insulin; however, are associated with a lower risk versus thiazolidinediones.
AIMS: Mixed evidence exists for the effect of incretin-based therapies on osteoporosis in type-2 diabetes. Therefore, we conducted a cohort study to determine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and common osteoporotic "fragility fractures" (upper extremity, hip, spine). METHODS: The UK-based Clinical Practice Research Datalink was used to identify adults without prior fractures receiving a new anti-diabetic drug or a new type-2 diabetes diagnosis between 2007 and 2016. The primary aim was to compare new-users of DPP-4 inhibitors versus new-users of sulfonylureas (SU). The association between DPP-4 inhibitors and incident fractures was estimated using Cox proportional hazards models. Deciles of high-dimensional propensity scores and other anti-diabetic drugs were used as covariates. RESULTS: We identified 7993 and 26,636 new-users of DPP-4 inhibitors and SUs, respectively. At cohort entry, the mean age was 58.8, 40% were female, mean diabetes duration was 1.3 years, and 42% had A1c > 9%. Over 9 years (mean follow-up = 1.2 years), the incident rate of fragility fractures was lower among DPP-4 versus SU users (3.0/1000 vs. 5.2/1000 person-years; P-value = 0.007). After adjustment, there was no statistically significant difference in fracture risk (hazard ratio adjusted, aHR = 0.80, 95%CI 0.51-1.24; P-value = 0.3125). In a secondary analysis, DPP-4 inhibitors were not associated with a difference in fracture risk compared to insulin (aHR = 0.91, 95%CI 0.40-2.09); however were associated with a lower fracture risk versus thiazolidinediones (aHR = 0.47, 95%CI 0.26-0.83). Sensitivity analyses supported findings. CONCLUSIONS:DPP-4 inhibitors are not associated with an increased risk of fragility fractures compared with SUs or insulin; however, are associated with a lower risk versus thiazolidinediones.
Authors: John-Michael Gamble; Jennifer R Donnan; Eugene Chibrikov; Laurie K Twells; William K Midodzi; Sumit R Majumdar Journal: Sci Rep Date: 2018-10-11 Impact factor: 4.379