Non-Insulin Antidiabetic Agents in the Management of Hyperglycaemia of Non-Critical Hospitalized Patients
DOI:
https://doi.org/10.20344/amp.20858Keywords:
Diabetes Mellitus, Type 2/ drug therapy, Hyperglycemia/drug therapy, Hypoglycemia, Hypoglycemic Agents/therapeutic useAbstract
Hyperglycaemia affects more than 30% of adults hospitalized for non-critical illness and is associated with an increased risk of adverse clinical outcomes. Insulin therapy is widely used for its safety and efficacy. However, given the growing availability of new drugs and new classes of antidiabetic agents with benefits beyond glycaemic control, challenges arise regarding their use in the hospital setting. This article aims to review and summarize the most recently available evidence and recommendations on the role of non-insulin antidiabetic agents in the management of hyperglycaemia in hospitalized patients. Insulin therapy remains the method of choice. Dipeptidyl peptidase 4 inhibitors can be considered in mild to moderate hyperglycaemia. Glucagon-like peptide 1 receptor agonists have recently shown promising results, with high efficacy in glycaemic control and low risk of hypoglycaemia. There are concerns regarding the increased risk of acidosis with metformin use, especially in cases of acute illness, although there is no evidence to support its suspension in selected patients with relative clinical stability. Sodium-glucose cotransporter-2 inhibitors should be discontinued in clinical situations that may predispose to ketoacidosis, including episodes of acute illness. The hospital use of sulfonylureas and thiazolidinediones is not advised.
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Sociedade Portuguesa de Diabetologia. Diabetes: factos e números – o ano de 2019, 2020 e 2021 − relatório anual do observatório nacional da diabetes 03/2023. 10ª ed. Lisboa: Letra Solúvel – Publicidade e Marketing, Lda; 2023.
Direção-Geral da Saúde. Programa nacional para a diabetes: desafios e estratégias 2023. Lisboa: DGS; 2023.
Godinho C, Jordão A, Dias A, Lopes A, Duarte A, Carvalho D, et al. Recomendações conjuntas da Sociedade Portuguesa de Diabetologia (SPD)/Sociedade Portuguesa de Medicina Interna (SPMI) sobre a abordagem e tratamento da hiperglicemia em internamento (não crítico). Rev Port Diabetes. 2015;10:127-46.
Korytkowski MT, Muniyappa R, Antinori-Lent K, Donihi AC, Drincic AT, Hirsch IB, et al. Management of hyperglycemia in hospitalized adult patients in non-critical care settings: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2022;107:2101-28. DOI: https://doi.org/10.1210/clinem/dgac278
Evans NR, Dhatariya KK. Assessing the relationship between admission glucose levels, subsequent length of hospital stay, readmission and mortality. Clin Med. 2012;12:137-9. DOI: https://doi.org/10.7861/clinmedicine.12-2-137
Roberts A, James J, Dhatariya K. Joint British Diabetes Societies (JBDS) for inpatient care. management of hyperglycaemia and steroid (glucocorticoid) therapy: a guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group. Diabet Med. 2018;35:1011-7. DOI: https://doi.org/10.1111/dme.13675
Pasquel FJ, Lansang MC, Dhatariya K, Umpierrez GE. Management of diabetes and hyperglycaemia in the hospital. Lancet Diabetes Endocrinol. 2021;9:174-88. DOI: https://doi.org/10.1016/S2213-8587(20)30381-8
Horton WB. Inpatient management of diabetes and hyperglycemia. In: Rodriguez-Saldana J, editors. The diabetes textbook. Cham: Springer; 2019: 655-68. DOI: https://doi.org/10.1007/978-3-030-11815-0_43
Kaneko S, Ueda Y, Tahara Y. GLP1 receptor agonist liraglutide is an effective therapeutic option for perioperative glycemic control in type 2 diabetes within Enhanced Recovery After Surgery (ERAS) protocols. Eur Surg Res. 2018;59:349-60. DOI: https://doi.org/10.1159/000494768
Galindo RJ, Dhatariya K, Gomez-Peralta F, Umpierrez GE. Safety and efficacy of inpatient diabetes management with non-insulin agents: an overview of international practices. Curr Diab Rep. 2022;22:237-46. DOI: https://doi.org/10.1007/s11892-022-01464-1
Clement S, Braithwaite SS, Magee MF, Ahmann A, Smith EP, Schafer RG, et al. American Diabetes Association Diabetes in Hospitals Writing Committee. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27:553-91. DOI: https://doi.org/10.2337/diacare.27.2.553
Montejano L, Vo L, McMorrow D. Transitions of care for people with type 2 diabetes: utilization of antihyperglycemic agents pre- and post-hospitalization. Diabetes Ther. 2016;7:91-103. DOI: https://doi.org/10.1007/s13300-015-0148-5
Pasquel FJ, Fayfman M, Umpierrez GE. Debate on insulin vs non-insulin use in the hospital setting-is it time to revise the guidelines for the management of inpatient diabetes? Curr Diab Rep. 2019;19:65. DOI: https://doi.org/10.1007/s11892-019-1184-8
Bishay RH, Meyerowitz-Katz G, Chandrakumar D, Jayaballa R, Hng TM, Mclean M, et al. Evaluating the diabetes-cardiology interface: a glimpse into the diabetes management of cardiology inpatients in western Sydney’s ‘diabetes hotspot’ and the establishment of a novel model of care. Diabetol Metab Syndr. 2018;10:90. DOI: https://doi.org/10.1186/s13098-018-0393-7
Ena J, Gómez-Huelgas R, Romero-Sánchez M, Gaviria AZ, Calzada-Valle A, Varela-Aguilar JM, et al; Diabetes and Obesity Working Group of the Spanish Society of Internal Medicine. Hyperglycemia management in patients admitted to internal medicine in Spain: a point-prevalence survey examining adequacy of glycemic control and guideline adherence. Eur J Intern Med. 2015;26:392-8. DOI: https://doi.org/10.1016/j.ejim.2015.04.020
Heaton PC, Desai VC, Kelton CM, Rajpathak SN. Sulfonylurea use and the risk of hospital readmission in patients with type 2 diabetes. BMC Endocr Disord. 2016;16:4.
Pasquel FJ, Gianchandani R, Rubin DJ, Dungan KM, Anzola I, Gomez PC, et al. Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial. Lancet Diabetes Endocrinol. 2017;5:125-33. DOI: https://doi.org/10.1016/S2213-8587(16)30402-8
Umpierrez GE, Gianchandani R, Smiley D, Jacobs S, Wesorick DH, Newton C, et al. Safety and efficacy of sitagliptin therapy for the inpatient management of general medicine and surgery patients with type 2 diabetes: a pilot, randomized, controlled study. Diabetes Care. 2013;36:3430-5. DOI: https://doi.org/10.2337/dc13-0277
Vellanki P, Rasouli N, Baldwin D, Alexanian S, Anzola I, Urrutia M, et al; Linagliptin Inpatient Research Group. Glycaemic efficacy and safety of linagliptin compared to a basal-bolus insulin regimen in patients with type 2 diabetes undergoing non-cardiac surgery: a multicentre randomized clinical trial. Diabetes Obes Metab. 2019;21:837-43. DOI: https://doi.org/10.1111/dom.13587
Garg R, Schuman B, Hurwitz S, Metzger C, Bhandari S. Safety and efficacy of saxagliptin for glycemic control in non-critically ill hospitalized patients. BMJ Open Diabetes Res Care. 2017;5:e000394. DOI: https://doi.org/10.1136/bmjdrc-2017-000394
Pérez-Belmonte LM, Gómez-Doblas JJ, Millán-Gómez M, López-Carmona MD, Guijarro-Merino R, Carrasco-Chinchilla F, et al. Use of linagliptin for the management of medicine department inpatients with type 2 diabetes in real-world clinical practice (lina-real-world study). J Clin Med. 2018;7:271. DOI: https://doi.org/10.3390/jcm7090271
European Medicines Agency. Vipidia: EPAR - Product Information. Committee for Medicinal Products for Human Use; First published: 15/10/2013; Last updated: 21/07/2023. [consultado 2024 jan 12]. Disponível em: https://www.ema.europa.eu/en/documents/product-information/vipidia-epar-productinformation_en.pdf.
Food and Drug Administration. FDA Drug Safety Communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin. 2014. [consultado 2023 jul 15]. Disponível em: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drugsafety-communication-fda-adds-warnings-about-heart-failure-risk-labels-type-2-diabetes.
White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, et al. EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327-35. DOI: https://doi.org/10.1056/NEJMoa1305889
Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, et al. SAVOR-TIMI 53 steering committee and investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317-26. DOI: https://doi.org/10.1056/NEJMoa1307684
ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al, on behalf of the American Diabetes Association. 16. Diabetes Care in the hospital: standards of care in diabetes-2023. Diabetes Care. 2023;46:S267-78. DOI: https://doi.org/10.2337/dc23-S016
Koufakis T, Mustafa OG, Zebekakis P, Kotsa K. Oral antidiabetes agents for the management of inpatient hyperglycaemia: so far, yet so close. Diabet Med. 2020;37:1418-26. DOI: https://doi.org/10.1111/dme.14329
ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al, on behalf of the American Diabetes Association. 9. pharmacologic approaches to glycemic treatment: standards of care in diabetes-2023. Diabetes Care. 2023;46:S140-57. DOI: https://doi.org/10.2337/dc23-S009
Polderman JA, van Steen SC, Thiel B, Godfried MB, Houweling PL, Hollmann MW, et al. Peri-operative management of patients with type-2 diabetes mellitus undergoing non-cardiac surgery using liraglutide, glucose-insulin-potassium infusion or intravenous insulin bolus regimens: a randomised controlled trial. Anaesthesia. 2018;73:332-9. DOI: https://doi.org/10.1111/anae.14180
Seisa MO, Saadi S, Nayfeh T, Muthusamy K, Shah SH, Firwana M, et al. A systematic review supporting the endocrine society clinical practice guideline for the management of hyperglycemia in adults hospitalized for noncritical illness or undergoing elective surgical procedures. J Clin Endocrinol Metab. 2022;107:2139-47. DOI: https://doi.org/10.1210/clinem/dgac277
Fayfman M, Galindo RJ, Rubin DJ, Mize DL, Anzola I, Urrutia MA, et al. A randomized controlled trial on the safety and efficacy of exenatide therapy for the inpatient management of general medicine and surgery patients with type 2 diabetes. Diabetes Care. 2019;42:450-6. DOI: https://doi.org/10.2337/dc18-1760
Seisa MO. Supplement for systematic review supporting the Endocrine Society Clinical Practice Guideline for the management of hyperglycemia in adults hospitalized for non-critical illness or undergoing elective surgical procedures. Figshare. Posted April 28, 2022. [consultado 2023 set 09]. Disponível em: https://figshare.com/articles/journal_contribution/Hyperglycemia_Supplement-docx/19668861/2
Muller C, Cheung NW, Dewey H, Churilov L, Middleton S, Thijs V, et al. Treatment with exenatide in acute ischemic stroke trial protocol: a prospective, randomized, open label, blinded end-point study of exenatide vs. standard care in post stroke hyperglycemia. Int J Stroke. 2018;13:857-62. DOI: https://doi.org/10.1177/1747493018784436
Mustafa OG, Whyte MB. The use of GLP-1 receptor agonists in hospitalised patients: an untapped potential. Diabetes Metab Res Rev. 2019;35:e3191. DOI: https://doi.org/10.1002/dmrr.3191
Bellolio MF, Gilmore RM, Ganti L. Insulin for glycaemic control in acute ischaemic stroke. Cochrane Database Syst Rev. 2014:CD005346. DOI: https://doi.org/10.1002/14651858.CD005346.pub4
Bladin C, Cheung N, Dewey H, Churilov L, Middleton S, Thijs V, et al. Treatment of hyperglycaemia in acute stroke: results from the trial of exenatide in acute ischaemic stroke (TEXAIS). Eur Stroke J. 2022;7:S546-88.
ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al, on behalf of the American Diabetes Association. 8. Obesity and weight management for the prevention and treatment of type 2 diabetes: standards of care in diabetes-2023. Diabetes Care. 2023;46:S128-39. DOI: https://doi.org/10.2337/dc23-S008
Thiruvenkatarajan V, Meyer EJ, Nanjappa N, Van Wijk RM, Jesudason D. Perioperative diabetic ketoacidosis associated with sodium-glucose cotransporter-2 inhibitors: a systematic review. Br J Anaesth. 2019;123:27-36. DOI: https://doi.org/10.1016/j.bja.2019.03.028
Koufakis T, Mustafa OG, Ajjan RA, Garcia-Moll X, Zebekakis P, Dimitriadis G, et al. The use of sodium-glucose co-transporter 2 inhibitors in the inpatient setting: Is the risk worth taking? J Clin Pharm Ther. 2020;45:883-91. DOI: https://doi.org/10.1111/jcpt.13107
Patakfalvi L, Brazeau AS, Dasgupta K. Physician experiences with sodium-glucose cotransporter (SGLT2) inhibitors, a new class of medications in type 2 diabetes, and adverse effects. Prim Health Care Res Dev. 2018;20:e50. DOI: https://doi.org/10.1017/S1463423618000476
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-28. DOI: https://doi.org/10.1056/NEJMoa1504720
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. DOI: https://doi.org/10.2337/dc15-1251
Food and Drug Administration. FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function. FDA; 2017. [consultado 2023 jul 04]. Disponível em: https://www.fda.gov/drugs/drug-safety-and-availability/fdadrug-safety-communication-fda-revises-warnings-regarding-use-diabetes-medicine-metformin-certain.
European Medicines Agency. EMA confirms recommendations to minimise ketoacidosis risk with SGLT2 inhibitors for diabetes. Committee for Medicinal Products for Human Use; 2016. [consultado 2024 jan 12]. Disponível em: https://www.ema.europa.eu/en/medicines/human/referrals/sglt2-inhibitors.
Gerards MC, Venema GE, Patberg KW, Kross M, Potter van Loon BJ, Hageman IMG, et al. Dapagliflozin for prednisone-induced hyperglycaemia in acute exacerbation of chronic obstructive pulmonary disease. Diabetes Obes Metab. 2018;20:1306-10. DOI: https://doi.org/10.1111/dom.13209
Huang W, Whitelaw J, Kishore K, Neto AS, Holmes NE, Marhoon N, et al. The comparative epidemiology and outcomes of hospitalized patients treated with SGLT2 or DPP4 inhibitors. J Diabetes Complications. 2021;35:108052. DOI: https://doi.org/10.1016/j.jdiacomp.2021.108052
Pasquel FJ, Klein R, Adigweme A, Hinedi Z, Coralli R, Pimentel JL, et al. Metformin-associated lactic acidosis. Am J Med Sci. 2015;349:263-7. DOI: https://doi.org/10.1097/MAJ.0b013e3182a562b7
Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2010:CD002967. DOI: https://doi.org/10.1002/14651858.CD002967.pub4
Cryer DR, Nicholas SP, Henry DH, Mills DJ, Stadel BV. Comparative outcomes study of metformin intervention versus conventional approach the COSMIC Approach Study. Diabetes Care. 2005;28:539-43. DOI: https://doi.org/10.2337/diacare.28.3.539
Sarfo-Adu BN, Hendley JL, Pick B, Oyibo SO. glycemic control during enteral tube feeding in patients with diabetes mellitus. Cureus. 2019;11:e3929. DOI: https://doi.org/10.7759/cureus.3929
The Association of British Clinical Diabetologists. The hospital management of hypoglycaemia in adults with diabetes mellitus. The Joint British Diabetes Societies for Inpatient Care (JBDS-IP); 2023. [consultado 2023 jul 07]. Disponível em: https://abcd.care/sites/default/files/site_uploads/JBDS_Guidelines_Current/JBDS_01_Hypo_Guideline_with_QR_code_January_2023.pdf.
Rajendran R, Kerry C, Rayman G; MaGIC Study Group. Temporal patterns of hypoglycaemia and burden of sulfonylurea-related hypoglycaemia in UK hospitals: a retrospective multicentre audit of hospitalised patients with diabetes. BMJ Open. 2014;4:e005165. DOI: https://doi.org/10.1136/bmjopen-2014-005165
Heaton PC, Desai VC, Kelton CM, Rajpathak SN. Sulfonylurea use and the risk of hospital readmission in patients with type 2 diabetes. BMC Endocr Disord. 2016;16:4. DOI: https://doi.org/10.1186/s12902-016-0084-z
Deusenberry CM, Coley KC, Korytkowski MT, Donihi AC. Hypoglycemia in hospitalized patients treated with sulfonylureas. Pharmacotherapy. 2012;32:613-7. DOI: https://doi.org/10.1002/j.1875-9114.2011.01088.x
Stuart K, Adderley NJ, Marshall T, Rayman G, Sitch A, Manley S, et al. Predicting inpatient hypoglycaemia in hospitalized patients with diabetes: a retrospective analysis of 9584 admissions with diabetes. Diabet Med. 2017;34:1385-91. DOI: https://doi.org/10.1111/dme.13409
Raskin P, Rendell M, Riddle MC, Dole JF, Freed MI, Rosenstock J; Rosiglitazone Clinical Trials Study Group. A randomized trial of rosiglitazone therapy in patients with inadequately controlled insulin-treated type 2 diabetes. Diabetes Care. 2001;24:1226-32. DOI: https://doi.org/10.2337/diacare.24.7.1226
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