Sodium-glucose cotransporter 2 (SGLT2) inhibitors and fracture risk in patients with type 2 diabetes mellitus: A meta-analysis

Diabetes/Metabolism Research and Reviews

Volumn 33, Issue 6, 2017, Pages

  Ruanpeng, Darin ^a   Ungprasert, Patompong ^b   Sangtian, Jutarat ^a   Harindhanavudhi, Tasma ^a  

^a UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^b MAYO CLINIC   (United States)

Author keywords

fracture; SGLT2 inhibitor; type 2 diabetes

Indexed keywords

CANAGLIFLOZIN; DAPAGLIFLOZIN; EMPAGLIFLOZIN; PLACEBO; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; 2-(3-(4-ETHOXYBENZYL)-4-CHLOROPHENYL)-6-HYDROXYMETHYLTETRAHYDRO-2H-PYRAN-3,4,5-TRIOL; BENZHYDRYL DERIVATIVE; GLUCOSIDE; SLC5A2 PROTEIN, HUMAN; SODIUM GLUCOSE COTRANSPORTER 2;

ARTICLE; COMPARATIVE EFFECTIVENESS; DIABETIC PATIENT; DRUG EFFICACY; EMBASE; FRACTURE; HUMAN; MEDLINE; META ANALYSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; RISK; RISK ASSESSMENT; SYSTEMATIC REVIEW; TREATMENT DURATION; TREATMENT OUTCOME; ANTAGONISTS AND INHIBITORS; COMPLICATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK FACTOR; STATISTICS AND NUMERICAL DATA;

BENZHYDRYL COMPOUNDS; CANAGLIFLOZIN; DIABETES MELLITUS, TYPE 2; FRACTURES, BONE; GLUCOSIDES; HUMANS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RISK FACTORS; SODIUM-GLUCOSE TRANSPORTER 2;

EID: 85029158143     PISSN: 15207552     EISSN: 15207560     Source Type: Journal    
DOI: 10.1002/dmrr.2903     Document Type: Article

References (50)

1. Leslie WD, Rubin MR, Schwartz AV, Kanis JA. Type 2 diabetes and bone. J Bone Miner Res. 2012;27:2231-2237.
2. Schwartz AV, Hillier TA, Sellmeyer DE, et al. Older women with diabetes have a higher risk of falls: a prospective study. Diabetes Care. 2002;25:1749-1754.
3. Ivers RQ, Cumming RG, Mitchell P, Peduto AJ. Diabetes and risk of fracture: The Blue Mountains Eye Study. Diabetes Care. 2001;24:1198-1203.
4. Schwartz AV. Diabetes mellitus: does it affect bone? Calcif Tissue Int. 2003;73:515-519.
5. Strotmeyer ES, Cauley JA, Schwartz AV, et al. Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults: the health, aging, and body composition study. Arch Intern Med. 2005;165:1612-1617.
6. Kahn SE, Zinman B, Lachin JM, et al. Rosiglitazone-associated fractures in type 2 diabetes: an analysis from a diabetes outcome progression trial (ADOPT). Diabetes Care. 2008;31:845-851.
7. Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet. 2009;373:2125-2135.
8. Aubert RE, Herrera V, Chen W, Haffner SM, Pendergrass M. Rosiglitazone and pioglitazone increase fracture risk in women and men with type 2 diabetes. Diabetes Obes Metab. 2010;12:716-721.
9. Hattersley AT, Thorens B. Type 2 diabetes, SGLT2 inhibitors, and glucose secretion. N Engl J Med. 2015;373:974-976.
10. Kwon H. Canagliflozin: clinical efficacy and safety. Endocrinology and Metabolic Durgs Advisory Commitee Meeting; 2013 [www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM336234.pdf]
11. Kohan DE, Fioretto P, Tang W, List JF. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int. 2014;85:962-971.
12. Nauck MA, Del Prato S, Meier JJ, et al. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care. 2011;34:2015-2022.
13. List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-glucose cotransport inibition with dapagliflozin in type 2 diabetes. Diabetes Care. 2009;32:650-657.
14. Ljunggren O, Bolinder J, Johansson L, et al. Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin. Diabetes Obes Metab. 2012;14:990-999.
15. 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.
16. Rosenstock J, Aggarwal N, Polidori D, et al. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitors, as add-on to metformin in subjects with type 2 diabetes. Diabetes Care. 2012;35:1232-1238.
17. Bays HE, Weinstein R, Law G, Canovatchel W. Canagliflozin: effects in overweight and obese subjects without diabetes mellitus. Obesity (Silver Spring). 2014;22:1042-1049.
18. Rosenstock J, Seman LJ, Jelaska A, et al. Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitors, as add-on to metformin in type 2 diabetes with mild hyperglycaemia. Diabetes Obes Metab. 2013;15:1154-1160.
19. Ferrannini E, Seman L, Seewaldt-Becker E, Hantel S, Pinnetti S, Woerle HJ. A phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitors empagliflozin in patients with type 2 diabetes. Diabetes Obes Metab. 2013;15:721-728.
20. Ferrannini E, Berk A, Hantel S, et al. Long-term safety and efficacy of empagliflozin, sitagliptin, and metformin: an active-controlled, parallel-group, randomized, 78-week open-label extension study in patients with type 2 diabetes. Diabetes Care. 2013;36:4015-4021.
21. Roden M, Merker L, Christiansen AV, et al. Safety, tolerability and effects on cardiometabolic risk factors of empagliflozin monotherapy in drug-naive patients with type 2 diabetes: a double-blind extension of a phase III randomized controlled trial. Cardiovasc Diabetol. 2015;14:154
22. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1-12.
23. Hedges LV, Pigott TD. The power of statistical tests in meta-analysis. Psychol Methods. 2001;6:203-217.
24. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557-560.
25. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264-269. W64
26. Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemiccontrol with metformin: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375:2223-2233.
27. AstraZeneca; Bristol-Myers Squibb. Efficacy and safety in patients with type 2 diabetes mellitus and cardiovascular disease. In: ClinicalTrials.gov [Internet].Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Nov 1]. Available from: http://clinicaltrials.gov/show/NCT 01042977 NLM Identifier: NCT01042977
28. Wilding JP, Woo V, Soler NG, et al. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med. 2012;156:405-415.
29. Jabbour SA, Hardy E, Sugg J, Parikh S. Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Diabetes Care. 2014;37:740-750.
30. Rosenstock J, Hansen L, Zee P, et al. Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin. Diabetes Care. 2015;38:376-383.
31. Janssen Research & Development, LLC. An efficacy, safety, and tolerability study of canagliflozin in patients with type 2 diabetes mellitus who have moderate renal impairment. In:ClinicalTrials.gov [Internet].Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Nov 1]. Available from: http://clinicaltrials.gov/show/NCT 01064414 NLM Identifier: NCT01064414
32. Lavalle-Gonzalez FJ, Januszewicz A, Davidson J, et al. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia. 2013;56:2582-2592.
33. Neal B, Perkovic V, de Zeeuw D, et al. Efficacy and safety of canagliflozin, an inhibitors of sodium-glucose cotransporter 2, when used in conjunction with insulin therapy in patients with type 2 diabetes. Diabetes Care. 2015;38:403-411.
34. Stenlof K, Cefalu WT, Kim KA, et al. Long-term efficacy and safety of canagliflozin monotherapy in patients with type 2 diabetes inadequately controlled with diet and exercise: findings from the 52-week CANTATA-M study. Curr Med Res Opin. 2014;30:163-175.
35. Janssen Research & Development, LLC. A safety and efficacy study of canagliflozin in older patients (55 to 80 years of age) with type 2 diabetes mellitus. In:ClinicalTrials.gov [Internet].Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Nov 1]. Available from: http://clinicaltrials.gov/show/NCT 01106651 NLM Identifier: NCT01106651
36. Janssen Research & Development, LLC. The CANTATA-MP trial (Canagliflozin Treatment and Trial Analysis—Metformin and Pioglitazone). In:ClinicalTrials.gov [Internet].Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Nov 1]. Available from: http://clinicaltrials.gov/show/NCT 01106690 NLM Identifier: NCT 01106690
37. Inagaki N, Kondo K, Yoshinari T, Takahashi N, Susuta Y, Kuki H. Efficacy and safety of canagliflozin monotherapy in Japanese patients with type 2 diabetes inadequately controlled with diet and exercise: a 24-week, randomized, double-blind, placebo-controlled, phase III study. Expert Opin Pharmacother. 2014;15:1501-1515.
38. Janssen Research & Development, LLC. The CANTATA-MSU Trial (Canagliflozin Treatment and Trial Analysis—Metformin and Sulphonylurea). In:ClinicalTrials.gov [Internet].Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Nov 1]. Available from: http://clinicaltrials.gov/show/NCT 01106625 NLM Identifier: NCT01106625
39. Boehringer Ingelheim; Eli Lilly and Company. Efficacy and safety of BI 10773 in combination with insulin in patients with type 2 diabetes. In:ClinicalTrials.gov [Internet].Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Nov 1]. Available from: http://clinicaltrials.gov/show/NCT 01011868 NLM Identifier: NCT01011868
40. Haring HU, Merker L, Seewaldt-Becker E, et al. Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2013;36:3396-3404.
41. Barnett AH, Mithal A, Manassie J, et al. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2014;2:369-384.
42. Roden M, Weng J, Eilbracht J, et al. Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2013;1:208-219.
43. Kovacs CS, Seshiah V, Merker L, et al. Empagliflozin as add-on therapy to pioglitazone with or without metformin in patients with type 2 diabetes mellitus. Clin Ther. 2015;37:1773-1788. e1
44. Rosenstock J, Jelaska A, Frappin G, et al. Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care. 2014;37:1815-1823.
45. 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;101:157-66.43.
46. Cefalu WT et al. Efficacy and safety of canagliflozin versus glimepiride inpatients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet. 2013;382:941-950.
47. Schernthaner G, Gross JL, Rosenstock J, et al. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care. 2013;36:2508-2515.
48. Meier C, Schwartz AV, Egger A, Lecka-Czernik B. Effects of diabetes drugs on the skeleton. Bone. 2016;82:93-100.
49. Monami M, Dicembrini I, Antenore A, Mannucci E. Dipeptidyl peptidase-4 inhibitors and bone fractures: a meta-analysis of randomized clinical trials. Diabetes Care. 2011;34:2474-2476.
50. Taylor SI, Blau JE, Rother KI. Possible adverse effects of SGLT2 inhibitors on bone. Lancet Diabetes Endocrinol. 2015;3:8-10.