Practical aspects of initiation and use of SGLT2 inhibitors: inpatient and outpatient perspectives
https://doi.org/10.14341/DM12855
Abstract
In today`s therapy of type 2 diabetes mellitus, SGLT2 inhibitors have taken their rightful place both due to their positive hypoglycemic and outstanding cardiorenometabolic effects. Recent randomized clinical trials, such as DAPA HF, EMPEROR-Reduced and EMPEROR-Preserved, show the benefits of their use in the treatment of patients with chronic heart failure without regard to the status of type 2 diabetes mellitus and so significantly expands the range of use of SGLT2 in the practice of doctors of various specialties. This review presents not only the results of the most significant studies of SGLT2 inhibitors, but also the main approaches to the starting therapy with this class of drugs in various clinical situations, both inpatient and outpatient. In addition, potential adverse events and limitations associated with the use of SGLT2 inhibitors are discussed in detail, which must be taken into account when prescribing in particular patient. The practical aspects of SGLT2 inhibitors` prescription are considered separately through the prism of their safe use in the perioperative and postinfarction periods, as well as during other special conditions. Particular attention is paid to the monitoring of physical and general examination data and laboratory instrumental tests, the consideration of which will minimize adverse events and best benefit for many cardiological, endocrinological and nephrological patients.
About the Authors
V. V. SalukhovRussian Federation
Vladimir V. Salukhov, MD, PhD
6, Academician Lebedev St., Saint-Petersburg, 194044
eLibrary SPIN: 4531-6011
G. R. Galstyan
Russian Federation
Gagik R. Galstyan, MD, PhD, Professor
Moscow
eLibrary SPIN: 9815-7509
T. A. Ilyinskay
Russian Federation
Tatiana A. Ilyinskaya, MD, PhD
Saint-Petersburg
eLibrary SPIN: 5734-7868
References
1. Tancredi M, Rosengren A, Svensson A-M, et al. Excess Mortality among Persons with Type 2 Diabetes. N Engl J Med. 2015;373(18):1720-1732. doi: https://doi.org/10.1056/NEJMoa1504347
2. Mintz ML. Role of the Kidney in Type 2 Diabetes and Mechanism of Action of Sodium Glucose Cotransporter-2 Inhibitors. JFP-Diabetes. [Internet] 2016;65(12) Available from: https://www.mdedge.com/content/role-kidney-type-2-diabetes-and-mechanism-actionsodium-glucose-cotransporter-2-inhibitors
3. Verbovoy AF, Verbovaya NI, Dolgikh YA. Symbiosis of cardiology and endocrinology. Med Counc. 2020;14:80-89. (In Russ.). doi: https://doi.org/10.21518/2079-701X-2020-14-80-89
4. Rubtsov YE, Kryukov EV, Khalimov YS. Vascular aging and type 2 diabetes mellitus. Endocrinol News, Opin Train. 2021;10(1):52-61. (In Russ.)]. doi: https://doi.org/10.33029/2304-9529-2021-10-1-52-61
5. Salukhov VV, Kotova ME. Main effects caused by SGLT2 inhibitors in patients with type 2 diabetes and the mechanisms that determine them. Endocrinol News, Opin Train. 2019;8(3):61-74. (In Russ.). doi: https://doi.org/10.24411/2304-9529-2019-13007
6. Fitchett D, Zinman B, Wanner C, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Eur Heart J. 2016;37(19):1526-1534. doi: https://doi.org/10.1093/eurheartj/ehv728
7. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128. doi: https://doi.org/10.1056/NEJMoa1504720
8. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377(7):644-657. doi: https://doi.org/10.1056/NEJMoa1611925
9. Shestakova MV. DECLARE-TIMI 58 trial in the context of EMPA-REG OUTCOME and CANVAS. Diabetes mellitus. 2020;22(6):592-601. (In Russ.). doi: https://doi.org/10.14341/DM10289
10. Salukhov VV, Ilyinskaya TA. New SGLT2 inhibitor ertugliflozin: safe and effective in the management of type 2 diabetes. Med Counc. 2020;7:32-41. (In Russ.). doi: https://doi.org/10.21518/2079-701X-2020-7-32-41
11. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347-357. doi: https://doi.org/10.1056/NEJMoa1812389
12. Batyushin MM. The dapagliflozin and prevention of adverse outcomes in chronic kidney disease: results of the DAPA-CKD study. Terapevticheskii arkhiv. 2021;93(6):713-723. (In Russ.). doi: https://doi.org/10.26442/00403660.2021.6.200891
13. Dedov II, Shestakova MV, Mayorov AYu, et al. Standards of specialized diabetes care. Diabetes Mellitus. 2019;22(S1):1-144 (In Russ.). doi: https://doi.org/10.14341/DM221S1
14. Salukhov VV, Khalimov YS, Shustov SB, Popov SI. SGLT2 inhibitors and kidneys: mechanisms and main effects in diabetes mellitus patients. Diabetes mellitus. 2021;23(5):475-491. (In Russ.). doi: https://doi.org/10.14341/DM12123
15. Rhee JJ, Jardine MJ, Chertow GM, Mahaffey KW. Dedicated kidney disease‐focused outcome trials with sodium‐glucose cotransporter‐2 inhibitors: Lessons from CREDENCE and expectations from DAPA‐HF, DAPA‐CKD, and EMPA‐KIDNEY. Diabetes, Obes Metab. 2020;22(S1):46-54. doi: https://doi.org/10.1111/dom.13987
16. Bozkurt B, Coats AJS, Tsutsui H, et al. Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition. Eur J Heart Fail. 2021;23(3):352-380. doi: https://doi.org/10.1002/ejhf.2115
17. Anker SD, Butler J, Filippatos GS, Jamal W, Salsali A, Schnee J, Kimura K, Zeller C, George J, Brueckmann M, Zannad F, Packer M; EMPEROR-Preserved Trial Committees and Investigators. Evaluation of the effects of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR-Preserved Trial. Eur J Heart Fail. 2019 Oct;21(10):1279-1287. doi: 10.1002/ejhf.1596
18. Williams DM, Evans M. Are SGLT-2 Inhibitors the Future of Heart Failure Treatment? The EMPEROR-Preserved and EMPEROR-Reduced Trials. Diabetes Ther. 2020;11(9):1925-1934. doi: https://doi.org/10.1007/s13300-020-00889-9
19. Villevalde SV., Galyavich AS, Vinogradova NG, et al. Resolution of an online meeting of the Volga Federal District experts on the EMPEROR-Reduced trial “A new era in the treatment of patients with HF. From EMPA-REG OUTCOME to EMPERORReduced trial.” Russ J Cardiol. 2021;26(2S):4562. (In Russ.). doi: https://doi.org/10.15829/1560-4071-2021-4562
20. Dedov II, Shestakova MV, Mayorov AYu, et al. Standards of specialized diabetes care. Diabetes Mellitus. 2021;24(S1):1-232. (In Russ.). doi: https://doi.org/10.14341/DM12802
21. 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(5):369-384. doi: https://doi.org/10.1016/S2213-8587(13)70208-0
22. Gulsin GS, Graham-Brown MPM, Squire IB, et al. Benefits of sodium glucose cotransporter 2 inhibitors across the spectrum of cardiovascular diseases. Heart. 2022;108(1):16-21. doi: https://doi.org/10.1136/heartjnl-2021-319185
23. Cherney DZI, Udell JA. Use of Sodium Glucose Cotransporter 2 Inhibitors in the Hands of Cardiologists. Circulation. 2016;134(24):1915-1917. doi: https://doi.org/10.1161/CIRCULATIONAHA.116.024764
24. Gomez-Peralta F, Abreu C, Lecube A, et al. Practical Approach to Initiating SGLT2 Inhibitors in Type 2 Diabetes. Diabetes Ther. 2017;8(5):953-962. doi: https://doi.org/10.1007/s13300-017-0277-0
25. Cai Y, Shi W, Xu G. The efficacy and safety of SGLT2 inhibitors combined with ACEI/ARBs in the treatment of type 2 diabetes mellitus: A meta-analysis of randomized controlled studies. Expert Opin Drug Saf. 2020;19(11):1497-1504. doi: https://doi.org/10.1080/14740338.2020.1817378
26. Lam D, Shaikh A. Real-Life Prescribing of SGLT2 Inhibitors: How to Handle the Other Medications, Including GlucoseLowering Drugs and Diuretics. Kidney360. 2021;2(4):742-746. doi: https://doi.org/10.34067/KID.0000412021
27. Colacci M, Fralick J, Odutayo A. et al. Sodium-Glucose Cotransporter-2 Inhibitors and Risk of Diabetic Ketoacidosis Among Adults With Type 2 Diabetes: A Systematic Review and Meta-Analysis. Can J Diabetes. 2022;46(1):10-15. doi: https://doi.org/10.1016/j.jcjd.2021.04.006
28. Pfützner A, Klonoff D, Heinemann L, et al. Euglycemic ketosis in patients with type 2 diabetes on SGLT2-inhibitor therapy—an emerging problem and solutions offered by diabetes technology. Endocrine. 2017;56(1):212-216. doi: https://doi.org/10.1007/s12020-017-1264-y
29. Somagutta M R, Agadi K, Hange N, et al. Euglycemic Diabetic Ketoacidosis and Sodium-Glucose Cotransporter-2 Inhibitors: A Focused Review of Pathophysiology, Risk Factors, and Triggers. Cureus. 2021;13(3):e13665. doi: https://doi.org/10.7759/cureus.13665
30. Burke KR, Schumacher CA, Harpe SE. SGLT2 Inhibitors: A Systematic Review of Diabetic Ketoacidosis and Related Risk Factors in the Primary Literature. Pharmacother J Hum Pharmacol Drug Ther. 2017;37(2):187-194. doi: https://doi.org/10.1002/phar.1881
31. 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(5):512-517. doi: https://doi.org/10.1038/nm.3828
32. Goldenberg RM, Berard LD, Cheng AYY, et al. SGLT2 Inhibitor–associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis. Clin Ther. 2016;38(12):2654-2664.e1. doi: https://doi.org/10.1016/j.clinthera.2016.11.002
33. Handelsman Y, Henry RR, Bloomgarden ZT, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Position Statement on the Association of SGLT-2 Inhibitors and Diabetic Ketoacidosis. Endocr Pract. 2016;22(6):753-762. doi: https://doi.org/10.4158/EP161292.PS
34. Bonora BM, Avogaro A, Fadini GP. Sodium‐glucose co‐transporter‐2 inhibitors and diabetic ketoacidosis: A n updated review of the literature. Diabetes, Obes Metab. 2018;20(1):25-33. doi: https://doi.org/10.1111/dom.13012
35. Storgaard H, Bagger JI, Knop FK, et al. Diabetic Ketoacidosis in a Patient with Type 2 Diabetes After Initiation of Sodium-Glucose Cotransporter 2 Inhibitor Treatment. Basic Clin Pharmacol Toxicol. 2016;118(2):168-170. doi: https://doi.org/10.1111/bcpt.12457
36. Staplin N, Roddick AJ, Emberson J, et al. Net effects of sodium-glucose co-transporter-2 inhibition in different patient groups: a meta-analysis of large placebo-controlled randomized trials. eClinicalMedicine. 2021;41(2):101163. doi: https://doi.org/10.1016/j.eclinm.2021.101163
37. McGovern AP, Hogg M, Shields BM, et al. Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation. BMJ Open Diabetes Res Care. 2020;8(1):e001238. doi: https://doi.org/10.1136/bmjdrc-2020-001238
38. Unnikrishnan A, Kalra S, Purandare V, Vasnawala H. Genital infections with sodium glucose cotransporter-2 inhibitors: Occurrence and management in patients with type 2 diabetes mellitus. Indian J Endocrinol Metab. 2018;22(6):837. doi: https://doi.org/10.4103/ijem.IJEM_159_17
39. Farr A, Effendy I, Frey Tirri B, et al. Guideline: Vulvovaginal candidosis (AWMF 015/072, level S2k). Mycoses. 2021;64(6):583-602. doi: https://doi.org/10.1111/myc.13248
40. Rådholm K, Figtree G, Perkovic V, et al. Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus. Circulation. 2018;138(5):458-468. doi: https://doi.org/10.1161/CIRCULATIONAHA.118.034222
41. Ryan PB, Buse JB, Schuemie MJ, et al. Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non‐ SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real‐world meta‐analysis of 4 observational databases (OBSER. Diabetes, Obes Metab. 2018;20(11):2585-2597. doi: https://doi.org/10.1111/dom.13424
42. Buse JB, Wexler DJ, Tsapas A, et al. 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2020;43(2):487-493. doi: https://doi.org/10.2337/dci19-0066
43. Zwart K, Velthuis S, Polyukhovych YV, et al. Sodiumglucose cotransporter 2 inhibitors: a practical guide for the Dutch cardiologist based on real-world experience. Netherlands Hear J. 2021;29(10):490-499. doi: https://doi.org/10.1007/s12471-021-01580-9
44. Nathan DM. Long-term complications of diabetes mellitus. N Engl J Med. 2017;3(28):76-85
45. Milder DA, Milder TY, Kam PCA. Sodium-glucose cotransporter type-2 inhibitors: pharmacology and perioperative considerations. Anaesthesia. 2018;73(8):1008-1018. doi: https://doi.org/10.1111/anae.14251
46. Handelsman Y, Henry RR, Bloomgarden ZT, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Position Statement on the Association of SGLT-2 Inhibitors and Diabetic Ketoacidosis. Endocr Pract. 2016;22(6):753-762. doi: https://doi.org/10.4158/EP161292.PS
47. Mazer CD, Arnaout A, Connelly KA, et al. Sodium-glucose cotransporter 2 inhibitors and type 2 diabetes: clinical pearls for in-hospital initiation, in-hospital management, and postdischarge. Curr Opin Cardiol. 2020;35(2):178-186. doi: https://doi.org/10.1097/HCO.0000000000000704
48. Kim DA, Anishchenko VV. Bariatricheskaya khirurgiya v upravlenii sakharnym diabetom 2 tipa. Sakharnyi diabet-2021: ot monitoringa k upravleniyu. Novosibirsk, 2021. P. 56-59. (In Russ.).
49. Thiruvenkatarajan V, Meyer EJ, Nanjappa N, et al. Perioperative diabetic ketoacidosis associated with sodium-glucose cotransporter-2 inhibitors: a systematic review. Br J Anaesth. 2019;123(1):27-36. doi: https://doi.org/10.1016/j.bja.2019.03.028
50. Andreadou I, Bell RM, Bøtker HE, Zuurbier CJ. SGLT2 inhibitors reduce infarct size in reperfused ischemic heart and improve cardiac function during ischemic episodes in preclinical models. Biochim Biophys Acta - Mol Basis Dis. 2020;1866(7):165770. doi: https://doi.org/10.1016/j.bbadis.2020.165770
51. Von Lewinski D, Benedikt M, Tripolt N, et al. Can sodium glucose cotransporter 2 (SGLT-2) inhibitors be beneficial in patients with acute myocardial infarction? Kardiol Pol. 2021;1866(7):165770. doi: https://doi.org/10.33963/KP.15969
52. Levine JA, Karam SL, Aleppo G. SGLT2-I in the Hospital Setting: Diabetic Ketoacidosis and Other Benefits and Concerns. Curr Diab Rep. 2017;17(7):54. doi: https://doi.org/10.1007/s11892-017-0874-3
Supplementary files
|
1. Рисунок 1. Механизмы, лежащие в основе диабетического эугликемического кетоацидоза на фоне приема ингибиторов натрий-глюкозного котранспортера 2 типа. Адаптировано из [29]. Примечание. СЖК - свободные жирные кислоты. иSGLT2 - ингибиторы натрий-глюкозного котранспортера 2 типа | |
Subject | ||
Type | Исследовательские инструменты | |
View
(290KB)
|
Indexing metadata ▾ |
|
2. Рисунок 2. Алгоритм коррекции сахароснижающей терапии при назначении ингибитора натрий-глюкозного котранспортера 2 типа. Адаптировано из [43]. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(346KB)
|
Indexing metadata ▾ |
|
3. Рисунок 3. Общие рекомендации по старту терапии ингибиторами натрий-глюкозного котранспортера 2 типа у пациентов с сахарным диабетом 2 типа и атеросклеротическими сердечно-сосудистыми заболеваниями в стационаре. Адаптировано из [47]. Примечание. ЭуДКА — диабетический эугликемический кетоацидоз. НПВП — нестереоидные противовоспалительные препараты. рСКФ —расчетная скорость клубочковой фильтрации. АД — артериальное давление. САД — систолическое артериальное давление. ДАД — диастолическое артериальное давление. иSGLT2 — ингибиторы натрий-глюкозного котранспортера 2 типа. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(367KB)
|
Indexing metadata ▾ |
Review
For citations:
Salukhov V.V., Galstyan G.R., Ilyinskay T.A. Practical aspects of initiation and use of SGLT2 inhibitors: inpatient and outpatient perspectives. Diabetes mellitus. 2022;25(3):275-287. (In Russ.) https://doi.org/10.14341/DM12855

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).