Sodium-glucose co-transporter-2 inhibitors and the risk of fractures of the upper or lower limbs in patients with type 2 diabetes: A nested case–control study

Diabetes, Obesity and Metabolism

Volumn 21, Issue 1, 2019, Pages 52-60

  Schmedt, Niklas ^a   Andersohn, Frank ^b,c   Walker, Jochen ^a   Garbe, Edeltraut ^d  

^a Institute for Applied Health Research Berlin (InGef)   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c Frank Andersohn Consulting and Research Services   (Germany)

^d UNIVERSITY OF BREMEN   (Germany)

Author keywords

bone; claims data; diabetes mellitus; fractures; Germany; hypoglycaemic agents; type 2

Indexed keywords

ALPHA GLUCOSIDASE INHIBITOR; CANAGLIFLOZIN; CANAGLIFLOZIN PLUS METFORMIN; DAPAGLIFLOZIN; DAPAGLIFLOZIN PLUS METFORMIN; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EMPAGLIFLOZIN; EMPAGLIFLOZIN PLUS METFORMIN; GLITAZONE DERIVATIVE; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; INSULIN; MEGLITINIDE; METFORMIN; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; SULFONYLUREA;

ADULT; AGED; ANKLE FRACTURE; ARM FRACTURE; ARTICLE; CASE CONTROL STUDY; CLINICAL ARTICLE; COHORT ANALYSIS; COMBINATION DRUG THERAPY; CONTROLLED STUDY; DISEASE ASSOCIATION; DISEASE SEVERITY; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG MEGADOSE; FALL RISK; FEMALE; FEMUR FRACTURE; FOLLOW UP; FOOT FRACTURE; FOREARM FRACTURE; HAND FRACTURE; HUMAN; HUMERUS FRACTURE; INCIDENCE; LEG FRACTURE; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MONOTHERAPY; NON INSULIN DEPENDENT DIABETES MELLITUS; RISK FACTOR; SHOULDER FRACTURE; THERAPEUTIC INDEX; TREATMENT DURATION; TREATMENT OUTCOME; WRIST FRACTURE; YOUNG ADULT; FRACTURE; GERMANY; MIDDLE AGED; VERY ELDERLY;

AGED; AGED, 80 AND OVER; CASE-CONTROL STUDIES; DIABETES MELLITUS, TYPE 2; FEMALE; FRACTURES, BONE; GERMANY; HUMANS; MALE; MIDDLE AGED; RISK FACTORS; SODIUM-GLUCOSE TRANSPORTER 2 INHIBITORS;

EID: 85052837758     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.13480     Document Type: Article

References (28)

1. Scheen AJ. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs. 2015;75:33-59
2. European Medicines Agency. Summary of Product Characteristics - Empagliflozin (Jardiance). 2017. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/SGLT2_inhibitors_20/European_Commission_final_decision/WC500206515.pdf. Accessed March 16, 2017
3. European Medicines Agency. Summary of product characteristics - canagliflozin (Ivokana). 2017. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002649/WC500156456.pdf. Accessed March 16, 2017
4. European Medicines Agency. Summary of Product Characteristics - Dapagliflozin (Forxiga). 2017. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/SGLT2_inhibitors__20/European_Commission_final_decision/WC500206510.pdf. Accessed March 16, 2017
5. US Food and Drug Administration. Safety Alerts for Human Medical Products - Invokana and Invokamet (canagliflozin): Drug Safety Communication - New Information on Bone Fracture Risk and Decreased Bone Mineral Density. 2015. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm461876.htm. Accessed March 16, 2017
6. Watts NB, Bilezikian JP, Usiskin K, et al. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2016;101:157-166
7. Bilezikian JP, Watts NB, Usiskin K, et al. Evaluation of bone mineral density and bone biomarkers in patients with type 2 diabetes treated with canagliflozin. J Clin Endocrinol Metab. 2016;101:44-51
8. Tang HL, Li DD, Zhang JJ, et al. Lack of evidence for a harmful effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on fracture risk among type 2 diabetes patients: a network and cumulative meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2016;18:1199-1206
9. Wu JHY, Foote C, Blomster J, et al. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2016;4:411-419
10. Ruanpeng D, Ungprasert P, Sangtian J, Harindhanavudhi T. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and fracture risk in patients with type 2 diabetes mellitus: a meta-analysis. Diabetes Metab Res Rev. 2017;33:e2903
11. Kohler S, Zeller C, Iliev H, Kaspers S. Safety and tolerability of empagliflozin in patients with type 2 diabetes: pooled analysis of phase I-III clinical trials. Adv Ther. 2017;34:1707-1726
12. Toulis KA, Bilezikian JP, Thomas GN, et al. Initiation of dapagliflozin and treatment-emergent fractures. Diabetes Obes Metab. 2018;20:1070-1074
13. Andersohn F, Walker J. Characteristics and external validity of the German health risk institute (HRI) database. Pharmacoepidemiol Drug Saf. 2016;25:106-109
14. Landgraf R, Kellerer M, Fach E, et al. Praxisempfehlungen DDG/DGIM. Diabetol Stoffwechs. 2015;10(suppl 2):140-151
15. Lappe V, Koster I, Schubert I. Anti-diabetic medication during the first four years of treatment. A study based on claims data. Dtsch Med Wochenschr. 2017;142:e1-e9
16. Chang H-Y, Weiner JP, Richards TM, Bleich SN, Segal JB. Validating the adapted diabetes complications severity index in claims data. Am J Manag Care. 2012;18:721-726
17. Essebag V, Platt RW, Abrahamowicz M, Pilote L. Comparison of nested case-control and survival analysis methodologies for analysis of time-dependent exposure. BMC Med Res Methodol. 2005;5:5
18. Suissa S. The quasi-cohort approach in pharmacoepidemiology: upgrading the nested case-control study. Epidemiology. 2015;26:242-246
19. Neal B, Perkovic V, de Zeeuw D, et al. Rationale, design, and baseline characteristics of the canagliflozin cardiovascular assessment study (CANVAS)--a randomized placebo-controlled trial. Am Heart J. 2013;166:217-223
20. Mannucci E, Monami M. Bone fractures with sodium-glucose co-transporter-2 inhibitors: how real is the risk? Drug Saf. 2017;40:115-119
21. Taylor SI, Blau JE, Rother KI. Possible adverse effects of SGLT2 inhibitors on bone. Lancet Diabetes Endocrinol. 2015;3:8-10
22. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644-657
23. Dombrowski S, Kostev K, Jacob L. Use of dipeptidyl peptidase-4 inhibitors and risk of bone fracture in patients with type 2 diabetes in Germany-a retrospective analysis of real-world data. Osteoporos Int. 2017;8:2421-2428
24. Driessen JHM, Knapen LM, Geusens PPMM, van den Bergh JPW. Fracture risk reduction with use of dipeptidyl peptidase-4 inhibitors: is there immortal time bias? Osteoporos Int. 2017;28:2429-2430
25. Driessen JHM, van Onzenoort HAW, Starup-Linde J, et al. Use of dipeptidyl peptidase 4 inhibitors and fracture risk compared to use of other anti-hyperglycemic drugs. Pharmacoepidemiol Drug Saf. 2015;24:1017-1025
26. Driessen JHM, van Onzenoort HAW, Henry RMA, et al. Use of dipeptidyl peptidase-4 inhibitors for type 2 diabetes mellitus and risk of fracture. Bone. 2014;68:124-130
27. Fu J, Zhu J, Hao Y, Guo C, Zhou Z. Dipeptidyl peptidase-4 inhibitors and fracture risk: an updated meta-analysis of randomized clinical trials. Sci Rep. 2016;6:29104
28. Josse RG, Majumdar SR, Zheng Y, et al. Sitagliptin and risk of fractures in type 2 diabetes: results from the TECOS trial. Diabetes Obes Metab. 2017;19:78-86