Association of British Clinical Diabetologists (ABCD) position statement on the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in type 1 diabetes
Keywords:SGLT-2 inhibitors, type 1 diabetes, ketoacidosis, position statement
AbstractSGLT-2 inhibitors are currently neither licensed nor recommended in people with type 1 diabetes. The management of type 1 diabetes consists essentially of insulin treatment, monitoring and education. SGLT-2 inhibitors can be a useful adjunct to insulin treatment in improving glycaemic control. They may also potentially be helpful in reducing cardiovascular and renal complications in people with type 1 diabetes. However, further studies will be needed to establish this. SGLT-2 inhibitors can cause diabetic ketoacidosis and certain circumstances appear to increase this risk. They should therefore be used with caution all the time and only under specialist supervision. Higher amputation rates have been reported with some SGLT-2 inhibitors and hence they should be used with caution in patients with peripheral vascular disease.
National Institute for Health and Care Excellence (NICE). Type 1 diabetes in adults: diagnosis and management. NICE guideline [NG17]. London, 2016. https://www.nice.org.uk/guidance/ng17 (accessed 17 May 2018)
Vallon V. The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus. Annu Rev Med 2015;66:255–70. https://doi.org/10.1146/annurev-med-051013-110046.
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117–28. https://doi.org/10.1056/NEJMoa1504720
Vallon V, Thomson SC. Diabetes mellitus: Cardiovascular and renal benefits of SGLT2 inhibition: insights from CANVAS. Nat Rev Nephrol 2017;13:517–8. https://doi.org/10.1038/nrneph.2017.113
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377:644–57. https://doi.org/10.1056/NEJMoa1611925
Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016;375:323–34. https://doi.org/10.1056/NEJMoa1515920
National Institute for Health and Care Excellence (NICE). Cardiovascular disease: risk assessment and reduction, including lipid modification. Clinical guideline [CG181]. London, 2016. https://www.nice.org.uk/guidance/ cg181 (accessed 17 May 2018).
NHS digital. National Diabetes Audit 2016-17. https://files.digital.nhs.uk/pdf/s/k/national_diabetes_audit_2016-17_report_1__care_processes_and_treatment_targets.pdf (accessed 17 July 2018).
Armstrong AC, Ambale-Venkatesh B, Turkbey E, et al. Association of cardiovascular risk factors and myocardial fibrosis with early cardiac dysfunction in type 1 diabetes: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study. Diabetes Care 2017;40:405–11. https://doi.org/10.2337/dc16-1889
Matuleviciene-Anängen V, Rosengren A, Svensson AM, et al. Glycaemic control and excess risk of major coronary events in persons with type 1 diabetes. Heart 2017;103:1687–95. https://doi.org/10.1136/heartjnl-2016-311050
Gagnum V, Stene LC, Leivestad T, Joner G, Skrivarhaug T. Long-term mortality and end-stage renal disease in a type 1 diabetes population diagnosed at age 15–29 years in Norway. Diabetes Care 2017;40:38–45. https://doi.org/10.2337/dc16-1213.
Sharp P, Kilvert A, Dashora U, et al, for the Association of British Clinical Diabetologists (ABCD). Standards of care for management of adults with type 1 diabetes. https://abcd.care/sites/abcd.care/files/site_uploads/Type_1_standards_of_care.pdf (accessed 17 May 2018).
Nathan DM, for the DCCT/EDIC Research Group. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study at 30 years: overview. Diabetes Care 2014;37:9–16. https://doi.org/10.2337/dc13-2112
Purnell JQ, Hokanson JE, Marcovina SM, Steffes MW, Cleary PA, Brunzell JD. Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure: results from the DCCT. JAMA 1998;280:140–6. https://doi.org/10.1001/jama.280.2.140
Vella S, Buetow L, Royle P, Livingstone S, Colhoun HM, Petrie JR. The use of metformin in type 1 diabetes: a systematic review of efficacy. Diabetologia 2010;53:809–20. https://doi.org/10.1007/s00125-009-1636-9
Staels F, Moyson C, Mathieu C. Metformin as add-on to intensive insulin therapy in type 1 diabetes mellitus. Diabetes Obes Metab 2017;19:1463–7. https://doi.org/10.1111/dom.12948
Gillani SM, Singh BM. The use of liraglutide, a GLP-1 agonist, in obese people with type 1 diabetes. Br J Diabetes 2014;14:98–101. https://doi.org/10.15277/bjdvd.2014.022
Guo H, Fang C, Huang Y, Pei Y, Chen L, Hu J. The efficacy and safety of DPP4 inhibitors in patients with type 1 diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract 2016;121:184–91. https://doi.org/10.1016/j.diabres.2016.08.022
Dellepiane S, Nasr MB, Assi E, et al. Sodium glucose cotransporter inhibitors in type 1 diabetes. Pharmacol Res 2018;133:1–8. https://doi.org/10.1016/j.phrs.2018.04.018 [Epub ahead of print]
Henry RR, Rosenstock J, Edelman 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;38:412–19. https://doi.org/10.2337/dc13-2955
Pieber TR, Famulla S, Eilbracht J, et al. Empagliflozin as adjunct to insulin in patients with type 1 diabetes: a 4-week, randomized, placebo-controlled trial (EASE-1). Diabetes Obes Metab 2015;17:928–35. https://doi.org/10.1111/dom.12494
Dandona P, Mathieu C, Phillip M, et al; DEPICT-1 Investigators. 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. Lancet Diabetes Endocrinol 2017;5:864–76. https://doi.org/10.1016/S2213-8587(17)30308-X
Famulla S, Pieber TR, Eilbracht J, et al. Glucose exposure and variability with empagliflozin as adjunct to insulin in patients with type 1 diabetes: continuous glucose monitoring data from a 4-week, randomized, placebo- controlled trial (EASE-1). Diabetes Technol Ther 2017;19:49–60. https://doi.org/10.1089/dia.2016.0261
Rodbard HW, Peters AL, Slee A, Cao A, Traina SB, Alba M. The effect of canagliflozin, a sodium glucose cotransporter 2 inhibitor, on glycemic end points assessed by continuous glucose monitoring and patient-reported outcomes among people with type 1 diabetes. Diabetes Care 2017;40: 171–80. https://doi.org/10.2337/dc16-1353
Henry RR, Thakkar P, Tong C, Polidori D, Alba M. Efficacy and safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to insulin in patients with type 1 diabetes. Diabetes Care 2015;38:2258–65. https://doi.org/10.2337/dc15-1730
Biester T, Aschemeier B, Fath M, et al. Effects of dapagliflozin on insulin- requirement, glucose excretion and β-hydroxybutyrate levels are not related to baseline HbA1c in youth with type 1 diabetes. Diabetes Obes Metab 2017;19:1635–9. https://doi.org/10.1111/dom.12975
Yang Y, Pan H, Wang B, Chen S, Zhu H. Efficacy and safety of SGLT2 inhibitors in patients with type 1 diabetes: a meta-analysis of randomized controlled trials. Chinese Med Sci J 2017;32:22–7. https://doi.org/10.24920/ J1001-9242.2007.003
Yang Y, Chen S, Pan H, et al. Safety and efficiency of SGLT2 inhibitor combining with insulin in subjects with diabetes: systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 2017;96: e6944. https://doi.org/10.1097/MD.0000000000006944
Kuhadiya ND, Ghanim H, Mehta A, et al. Dapagliflozin as additional treatment to liraglutide and insulin in patients with type 1 diabetes. J Clin Endocrinol Metab 2016;101:3506–15. https://doi.org/10.1210/jc.2016-1451
European Pharmaceutical Review. EMA accepts marketing authorisation variation for Forxiga in adults with type-1 diabetes. https://www.europeanpharmaceuticalreview.com/news/73381/ema-forxiga-type-1-diabetes (accessed 16 May 2018).
Fadini GP, Bonora BM, Avogaro A. SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System. Diabetologia 2017;60:1385–9. https://doi.org/10.1007/s00125-017-4301-8
Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care 2015;38:1687–93. https://doi.org/10.2337/dc15-0843
Erondu N, Desai M, Ways K, Meininger G. Diabetic ketoacidosis and related events in the Canagliflozin Type 2 Diabetes Clinical Program. Diabetes Care 2015;38:1680–6. https://doi.org/10.2337/dc15-1251
Perkins BA, Cherney DZ, Partridge H, et al. Sodium glucose cotransporter 2 inhibition and glycemic control in type 1 diabetes: results of an 8-week open-label proof-of concept trial. Diabetes Care 2014;37:1480–3. https://doi.org/10.2337/dc13-2338
Roman R, Pereyra M, Ramirez C. Adolescent with type 1 diabetes on insulin and dapaglifozin a SGLT2 inhibitor developed an euglycemic diabetic ketosis. Horm Res Paediatr 2016;86:48.
Roman R, Valdivia N, Ruiz S. Overweight adolescents with type 1 diabetes may decrease body mass index, insulin dose and glucose variability on dapagliflozin, a SGLT2 inhibitor. Horm Res Paediatr 2016;86:73.
Bader N, Mirza L. Euglycemic diabetic ketoacidosis in a 27 year-old female patient with type-1-diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin. Pak J Med Sci 2016;32:786–8. https://doi.org/10.12669/pjms.323.9201
Ferrannini E, Baldi S, Frascerra S, et al. Shift to fatty substrate utilization in response to sodium-glucose cotransporter 2 inhibition in subjects without diabetes and patients with type 2 diabetes. Diabetes 2016;65:1190–5. https://doi.org/10.2337/db15-1356
Bonner C, Kerr-Conte J, Gmyr V, et al. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med 2015;21:512–17. https://doi.org/10.1038/nm.3828
Maruyama H, Hisatomi A, Orci L, et al. Insulin within islets is a physiologic glucagon release inhibitor. J Clin Invest 1984;74:2296–9. https://doi.org/10.1172/JCI111658
Henry RR, Dandona P, Pettus J, Mudaliar S, Xu J, Hansen L. Dapagliflozin in patients with type 1 diabetes: a post hoc analysis of the effect of insulin dose adjustments on 24 hour continuously monitored mean glucose and fasting β hydroxybutyrate levels in a phase IIa pilot study. Diabetes Obes Metab 2017;19:814–21. https://doi.org/10.1111/dom.12882
Li D, Yang JY, Wang T, Shen S, Tang H. Risks of diabetic foot syndrome and amputation associated with sodium glucose co-transporter 2 inhibitors: a meta-analysis of randomized controlled trials. Diabetes Metab 2018 Feb. https://doi.org/10.1016/j.diabet.2018.02.001 (accessed 17 May 2018)
Guo M, Ding J, Li J, et al. SGLT2 inhibitors and stroke risk in patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab 2018 Mar. https://doi.org/10.1111/dom.13295 (accessed 17 May 2018)
National Institutes of Health. Dapagliflozin evaluation in patients with inadequately controlled type 1 diabetes (DEPICT 2). http://clinicaltrials.gov/show/NCT02460978 (accessed 17 May 2018).
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