Dipeptidyl Peptidase-4 Inhibitors and Bone Fractures

Abstract

OBJECTIVEThiazolidinediones and insulin are associated with a higher risk of fractures in type 2 diabetic patients. Incretin hormones increase bone density in experimental models, but the effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on bone fractures has not been reported so far.RESEARCH DESIGN AND METHODSA meta-analysis was performed including all randomized clinical trials with a duration of at least 24 weeks, enrolling patients with type 2 diabetes, comparing DPP-4 inhibitors with placebo or active drugs.RESULTSTwenty-eight trials enrolling 11,880 and 9,175 patients for DPP-4 inhibitors and comparators, respectively, were included, reporting 63 fractures. DPP-4 inhibitors, compared with placebo or other treatments, were associated with a reduced risk of fractures (Mantel–Haenszel odds ratio [MH-OR] 0.60, 95% CI 0.37–0.99, P = 0.045), even after the exclusion of comparisons with thiazolidinediones or sulfonylureas (MH-OR 0.56, 0.33–0.93, P = 0.026).CONCLUSIONSThe present meta-analysis suggests that treatment with DPP-4 inhibitors could be associated with a reduced risk of bone fractures.

MANAGEMENT OF ENDOCRINE DISEASE: Diabetes and osteoporosis: cause for concern?

“…For the GLP1 agonists, liraglutide was associated with a decreased risk of fractures, whereas an increased risk was seen for exenatide (56). DPP-IV inhibitors may be associated with a decreased risk of fractures (57). However, similar observations have been made for the older antidiabetic drugs and may be related to their ability to control diabetes; for example, metformin may be associated with a decreased risk of fractures (55).…”

GLP-1 receptor agonists or DPP-4 inhibitors: How to guide the clinician?

“…39 Contrairement aux glitazones, les gliptines n'augmentent pas le risque de fractures osseuses et pourraient même être associées à une diminution de ce risque. 40 Une tendance à davantage d'infections bénignes des voies respiratoires supérieures a été rapportée incidemment, 41 mais non confirmée dans la plupart des essais cliniques contrôlés. 39,42 Un risque accru de pancréatite, voire de cancer du pancréas, a également été suspecté, mais sur la base de données rapportées exposées à des biais potentiels.…”

Novel skeletal effects of glucagon-like peptide-1 (GLP-1) receptor agonists

“…Furthermore, as discussed below, a reduction in bone fracture has been evidenced with DPP-4 inhibitors (Monami et al 2011). However, several differences exist between DPP-4 inhibitors and GLP-1RAs.…”

“…A meta-analysis carried out on 28 trials suggests a reduced fracture risk with DPP-4 inhibitors, dependent on the treatment duration (Monami et al 2011). However, not all studies are showing a positive effect of DPP-4 inhibitors on fracture risk, BMD and bone turnover (Monami et al 2011, Driessen et al 2014.…”

“…A meta-analysis carried out on 28 trials suggests a reduced fracture risk with DPP-4 inhibitors, dependent on the treatment duration (Monami et al 2011). However, not all studies are showing a positive effect of DPP-4 inhibitors on fracture risk, BMD and bone turnover (Monami et al 2011, Driessen et al 2014. Recent preclinical studies showed protective effect of DPP-4 inhibitors on the skeleton of diabetic rats (Glorie et al 2014, Eom et al 2016 while others have shown no effect (Gallagher et al 2014).…”