title: Effects of Incretin-Based Therapies and SGLT2 Inhibitors on Skeletal Health.
abstract: Anti-diabetic drugs are widely used and are essential for adequate glycemic control in patients with type 2 diabetes. Recently, marketed anti-diabetic drugs include incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors) and sodium-glucose co-transporter 2 (SGLT2) inhibitors. In contrast to well-known detrimental effects of thiazolidinediones on bone metabolism and fracture risk, clinical data on the safety of incretin-based therapies is limited. Based on meta-analyses of trials investigating the glycemic-lowering effect of GLP-1 receptor agonists and DPP4 inhibitors, it seems that incretin-based therapies are not associated with an increase in fracture risk. Sodium-glucose co-transporter 2 inhibitors may alter calcium and phosphate homeostasis as a result of secondary hyperparathyroidism induced by increased phosphate reabsorption. Although these changes may suggest detrimental effects of SGLT-2 inhibitors on skeletal integrity, treatment-related direct effects on bone metabolism seem unlikely. Observed changes in BMD, however, seem to result from increased bone turnover in the early phase of drug-induced weight loss. Fracture risk, which is observed in older patients with impaired renal function and elevated cardiovascular disease risk treated with SGLT2 inhibitors, seems to be independent of direct effects on bone but more likely to be associated with falls and changes in hydration status secondary to osmotic diuresis.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, University Hospital, Missionsstrasse 24, CH-4055, Basel, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Egger
authors.affiliation: Endonet, Endocrine Clinic and Laboratory, Basel, Switzerland.
authors.forename: Marius E
authors.initials: ME
authors.lastname: Kraenzlin
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, University Hospital, Missionsstrasse 24, CH-4055, Basel, Switzerland. christian.meier@unibas.ch.|Endonet, Endocrine Clinic and Laboratory, Basel, Switzerland. christian.meier@unibas.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Meier
mesh_terms: D000058:Accidental Falls; D015519:Bone Density; D016723:Bone Remodeling; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D050723:Fractures, Bone / Q000453:epidemiology*; D006801:Humans; D054795:Incretins / Q000627:therapeutic use*; D012307:Risk Factors; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: DPP-4 inhibitors; Diabetes mellitus; Incretins; SGLT2 inhibitors