Volume 8, Issue 2 (Spring 2020)                   Iran J Health Sci 2020, 8(2): 45-58 | Back to browse issues page


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Saha S, Saha S. A Systematic Review and Meta-Analysis of Randomized Controlled Trials Comparing the Safety of Dapagliflozin in Type 1 Diabetes Patients. Iran J Health Sci. 2020; 8 (2) :45-58
URL: http://jhs.mazums.ac.ir/article-1-708-en.html
National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India , sumanta.saha@uq.net.au
Abstract:   (502 Views)
Background and Purpose: The dapagliflozin’s safety profile in insulin-treated adult type-1 diabetes mellites (T1DM) patients remains poorly explored. Therefore, this systematic review and meta-analysis compared the risk of all-cause side effects, study discontinuation of participants due to side effects, urinary tract infection (UTI), diabetic ketoacidosis, and hypoglycemia between dapagliflozin 10 mg and dapagliflozin 5 mg, dapagliflozin 10 mg and placebo, and dapagliflozin 5 mg and placebo.
Materials and Methods: Parallel-arm randomized controlled trials juxtaposing the above outcomes between the afore-mentioned interventions were eligible for inclusion in this study and were searched in PubMed, Embase, and Scopus. Utilizing the Cochrane tool, the risk of bias was assessed in the recruited trials. Finally, by random-effect meta-analysis, each outcome was compared among the above interventions, and the risk ratio was estimated.
Results: Four trials of varying length (1-52 weeks) sourcing data from almost 1760 participants from about 32 nations were reviewed. Overall, the trials had a low or unclear risk of bias, and only one was at a high risk of bias.  Compared to the placebo, the risk of side effects was higher in those treated with dapagliflozin 5 mg (RR=1.10; 95% CI=1.02-1.18; p=0.014; I2=0%). UTI risk was less with the 10mg dapagliflozin than its lower dose (RR=0.50; 95% CI=0.32-0.79; p-value=0.003; I2=0%). All the remaining comparisons were statistically not significantly different between the juxtaposed intervention pairs.
Conclusion: In contrast to placebo, dapagliflozin 5mg increased the risk of overall adversities in insulin-treated type-1 diabetes, and dapagliflozin 10 mg had a reduced risk of UTI than its 5mg preparation.
Full-Text [PDF 981 kb]   (122 Downloads)    
Type of Study: Original Article | Subject: Emergency Medicine

References
1. Lucier J, Weinstock RS. Diabetes Mellitus Type 1. In: StatPearls Treasure Island (FL): StatPearls Publishing. 2020.
2. Fattah H, Vallon V. The Potential Role of SGLT2 Inhibitors in the Treatment of Type 1 Diabetes Mellitus. Drugs. 2018 May;78(7):717-26. [DOI:10.1007/s40265-018-0901-y] [PMID] [PMCID]
3. Dellepiane S, Ben Nasr M, Assi E, Usuelli V, Letizia T, D'Addio F, et al. Sodium glucose cotransporters inhibitors in type 1 diabetes. Pharmacological research. 2018;133:1-8. [DOI:10.1016/j.phrs.2018.04.018] [PMID]
4. McCrimmon RJ, Henry RR. SGLT inhibitor adjunct therapy in type 1 diabetes. Diabetologia. 2018 Oct 22;61(10):2126-33. [DOI:10.1007/s00125-018-4671-6] [PMID] [PMCID]
5. Rieg T, Vallon V. Development of SGLT1 and SGLT2 inhibitors. Diabetologia. 2018;61(10):2079-86. [DOI:10.1007/s00125-018-4654-7] [PMID] [PMCID]
6. Saha S. An Appraisal of a Systematic Review and Meta-Analysis of Randomized Clinical Trials on the Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors as an Adjunct to Insulin Therapy in Type 1 Diabetes Patients. International Journal of Diabetes and Metabolism. 2019 Aug 22;1-1. [DOI:10.1159/000502743]
7. Saha S, Saha S. A Systematic Review and Meta-Analysis of Randomised Controlled Trials, Contrasting the Safety Profile between Sodium-Glucose Cotransporter-2 Inhibitors and Placebo in Type 1 Diabetes Mellitus Patients. International Journal of Diabetes and Metabolism. 2020 Feb 24;1-12. [DOI:10.1159/000506366]
8. Boeder S, Edelman S V. Sodium‐glucose co‐transporter inhibitors as adjunctive treatment to insulin in type 1 diabetes: A review of randomized controlled trials. Diabetes, Obesity and Metabolism. 2019 13;21(S2):62-77. [DOI:10.1111/dom.13749] [PMID] [PMCID]
9. Davidson JA. SGLT2 inhibitors in patients with type 2 diabetes and renal disease: overview of current evidence. Postgraduate Medicine. 2019 May 19;131(4):251-60. [DOI:10.1080/00325481.2019.1601404] [PMID]
10. List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-Glucose Cotransport Inhibition With Dapagliflozin in Type 2 Diabetes. Diabetes Care . 2009 Apr 1;32(4):650-7. [DOI:10.2337/dc08-1863] [PMID] [PMCID]
11. Meng W, Ellsworth BA, Nirschl AA, McCann PJ, Patel M, Girotra RN, et al. Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. Journal of medicinal chemistry. 2008 Mar 13;51(5):1145-9.
12. Mathieu C, Dandona P, Phillip M, Oron T, Lind M, Hansen L, et al. Glucose Variables in Type 1 Diabetes Studies With Dapagliflozin: Pooled Analysis of Continuous Glucose Monitoring Data From DEPICT-1 and -2. Diabetes Care. 2019 Jun;42(6):1081-7. [DOI:10.2337/dc18-1983] [PMID]
13. Editor. FDA rejects dapagliflozin as treatment add-on for type 1 diabetes - Diabetes. [cited 2020 Jun 23]. diabetes.co. uk/news/2019/jul/fda-rejects-dapagliflozin-as-treatment-add-on-for-type-1-diabetes-98751641.html
14. Saha S, Saha S. The comparison of efficacy and safety between different doses of empagliflozin in insulin-treated type 1 diabetes mellitus patients: a systematic review and meta-analysis protocol. Journal of diabetes and metabolic disorders. 2020 May 21; 19:545–550. [DOI:10.1007/s40200-020-00544-x] [PMID]
15. Saha S, Saha S. A systematic review and meta-analysis of randomized controlled trials, juxtaposing the control of glycemia and blood pressure between large dose empagliflozin and placebo among type 1 diabetes patients. International journal of health sciences. 2020 Feb 29;14(2):40-52. [DOI:10.1159/000506366]
16. Dandona P, Mathieu C, Phillip M, Hansen L, Griffen SC, Tschöpe D, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial. The lancet. Diabetes & endocrinology. 2017;5(11):864-76.
17. Mathieu C, Dandona P, Gillard P, Senior P, Hasslacher C, Araki E, et al. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-Week Results From a Randomized Controlled Trial. Diabetes Care . 2018 Sep;41(9):1938-46. [DOI:10.2337/dc18-0623] [PMID]
18. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Journal of Clinical Epidemiology. 2009 Oct;62(10):e1-34. [DOI:10.1016/j.jclinepi.2009.06.006] [PMID]
19. Higgins JPT GS (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. . The Cochrane Collaboration. 2011. www.cochrane-handbook.org
20. Watada H, Shiramoto M, Ueda S, Tang W, Asano M, Thorén F, et al. Pharmacokinetics and pharmacodynamics of dapagliflozin in combination with insulin in Japanese patients with type 1 diabetes. Diabetes, Obesity and Metabolism. 2019 Apr;21(4):876-82. [DOI:10.1111/dom.13593] [PMID] [PMCID]
21. Dandona P, Mathieu C, Phillip M, Hansen L, Tschöpe D, Thorén F, et al. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes: The DEPICT-1 52-Week Study. Diabetes Care. 2018;41(12):2552-9. [DOI:10.2337/dc18-1087] [PMID]
22. Henry RR, Rosenstock J, Edelman S, Mudaliar S, Chalamandaris A-G, Kasichayanula S, et al. Exploring the potential of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: a randomized, double-blind, placebo-controlled pilot study. Diabetes Care. 2015 Mar;38(3):412-9. [DOI:10.2337/dc13-2955] [PMID]
23. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P, others. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS med. 2009;6(7):e1000097. [DOI:10.1371/journal.pmed.1000097] [PMID] [PMCID]
24. Dandona P, Mathieu C, Phillip M, Hansen L, Griffen SC, Tschöpe D, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial. The lancet. Diabetes & endocrinology. 2017 Nov;5(11):864-76.
25. Henry RR, Rosenstock J, Edelman S, Mudaliar S, Chalamandaris A-G, Kasichayanula S, et al. Exploring the Potential of the SGLT2 Inhibitor Dapagliflozin in Type 1 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. Diabetes Care. 2015 Mar;38(3):412-9. [DOI:10.2337/dc13-2955] [PMID]
26. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004 Jun 19;328(7454):1490. [DOI:10.1136/bmj.328.7454.1490] [PMID] [PMCID]

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


© 2020 All Rights Reserved | Iranian Journal of Health Sciences

Designed & Developed by : Yektaweb