Oral antidiabetes agents for the management of inpatient hyperglycaemia: so far, yet so close
T. Koufakis
Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
Search for more papers by this authorO. G. Mustafa
Department of Diabetes, King’s College Hospital, London, UK
Search for more papers by this authorP. Zebekakis
Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
Search for more papers by this authorCorresponding Author
K. Kotsa
Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
Correspondence to: Kalliopi Kotsa. E-mail: [email protected]
Search for more papers by this authorT. Koufakis
Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
Search for more papers by this authorO. G. Mustafa
Department of Diabetes, King’s College Hospital, London, UK
Search for more papers by this authorP. Zebekakis
Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
Search for more papers by this authorCorresponding Author
K. Kotsa
Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
Correspondence to: Kalliopi Kotsa. E-mail: [email protected]
Search for more papers by this authorAbstract
Background
Hyperglycaemia is an ongoing challenge in hospital settings and is associated with poor outcomes. Current recommendations for the management of inpatient hyperglycaemia suggest insulin as the main glucose-lowering treatment choice and limit the administration of oral antidiabetes agents to a small proportion of cases because of safety concerns.
Aim
To present and critically appraise the available evidence on the use of oral antidiabetes agents in the hospital setting and the risk–benefit balance of such an approach in the era of cardiovascular outcomes trials.
Methods
PubMed, Embase and Google Scholar databases were searched to identify relevant published work. Available evidence on the efficacy and the safety profile of oral agents in the context of their use in hospitalized individuals are summarized and discussed in this narrative review.
Results
There is no robust evidence to suggest the use of metformin, thiazolidinediones, sulfonylureas and sodium-glucose co-transporter-2 inhibitors in the hospital setting, although some of their effects on acute outcomes deserve further evaluation in future studies. However, the use of dipeptidyl peptidase-4 inhibitors in inpatients with type 2 diabetes is supported by a few, well-designed, randomized controlled trials. These trials have demonstrated good safety and tolerability profiles, comparable to insulin glucose-lowering efficacy, and a reduction in insulin dose when dipeptidyl peptidase-4 inhibitors are co-administered with insulin, in individuals with mild to moderate hyperglycaemia and a stable clinical condition.
Conclusion
The administration of dipeptidyl peptidase-4 inhibitors to specific groups of inpatients might be a safe and effective alternative to insulin.
Supporting Information
| Filename | Description |
|---|---|
| dme14329-sup-0001-references.docxWord document, 15.1 KB | References S1–S17. Supplementary references. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Petite SE. Noninsulin medication therapy for hospitalized patients with diabetes mellitus. Am J Health Syst Pharm 2018; 75: 1361–1368.
- 2Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE. Hyperglycemia: an independent marker of inhospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab 2002; 87: 978–982.
- 3van Steen SC, Rijkenberg S, van der Voort PHJ, DeVries JH. The association of intravenous insulin and glucose infusion with intensive care unit and hospital mortality: a retrospective study. Ann Intensive Care 2019; 9: 29.
- 4 American Diabetes Association. 15. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes-2020. Diabetes Care 2020; 43: S193–S202.
- 5 Joint British Diabetes Societies (JBDS) for Inpatient Care Group. Management of adults with diabetes undergoing surgery. 2016. Available at https://abcd.care/joint-british-diabetes-societies-jbds-inpatient-care-group. Last accessed 3 January 2020.
- 6Kumar S, Molitch ME. Use of Insulin in the Inpatient Setting: Need for Continued Use. Curr Diab Rep 2019; 19: 64.
- 7Sathya B, Davis R, Taveira T, Whitlatch H, Wu WC. Intensity of peri-operative glycemic control and postoperative outcomes in patients with diabetes: a meta-analysis. Diabetes Res Clin Pract 2013; 102: 8–15.
- 8Umpierrez G, Cardona S, Pasquel F, Jacobs S, Peng L, Unigwe M et al. Randomized Controlled Trial of Intensive Versus Conservative Glucose Control in Patients Undergoing Coronary Artery Bypass Graft Surgery: GLUCO-CABG Trial. Diabetes Care 2015; 38: 1665–1672.
- 9Lake A, Arthur A, Byrne C, Davenport K, Yamamoto JM, Murphy HR. The effect of hypoglycaemia during hospital admission on health-related outcomes for people with diabetes: a systematic review and meta-analysis. Diabet Med 2019; 36: 1349–1359.
- 10Umpierrez GE, Korytkowski M. Is incretin-based therapy ready for the care of hospitalized patients with type 2 diabetes?: insulin therapy has proven itself and is considered the mainstay of treatment. Diabetes Care 2013; 36: 2112–2117.
- 11Umpierrez GE, Schwartz S. Use of incretin-based therapy in hospitalized patients with hyperglycemia. Endocr Pract 2014; 20: 933–944.
- 12Umpierrez 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: 3430–3435.
- 13Sultana G, Kapur P, Aqil M, Alam MS, Pillai KK. Drug utilization of oral hypoglycemic agents in a university teaching hospital in India. J Clin Pharm Ther 2010; 35: 267–277.
- 14Scotton DW, Wierman H, Coughlan A, Walters M, Kuhn C. Assessing the appropriate use of metformin in an inpatient setting and the effectiveness of two pharmacy-based measures to improve guideline adherence. Qual Manag Health Care 2009; 18: 71–76.
- 15Sharabash HM, Remington TL, Mar P, Winston R, Walker PC. Retrospective review of metformin in inpatients and outpatients at the University of Michigan. Diabetes Care 2006; 29: 170–171.
- 16Pasquel 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.
- 17Ramzan S, Timmins P, Hasan SS, Babar ZU. Cost analysis of type 2 diabetes mellitus treatment in economically developed countries. Expert Rev Pharmacoecon Outcomes Res 2019; 19: 5–14.
- 18Aljofan M, Riethmacher D. Anticancer activity of metformin: a systematic review of the literature. Future Sci OA 2019; 5: FSO410.
- 19Sarfo-Adu BN, Hendley JL, Pick B, Oyibo SO. Glycemic control during enteral tube feeding in patients with diabetes mellitus. Cureus 2019; 11: e3929.
- 20Mima Y, Kuwashiro T, Yasaka M, Tsurusaki Y, Nakamura A, Wakugawa Y et al. Impact of metformin on the severity and outcomes of acute ischemic stroke in patients with type 2 diabetes mellitus. J Stroke Cerebrovasc Dis 2016; 25: 436–446.
- 21Calabrese AT, Coley KC, DaPos SV, Swanson D, Rao RH. Evaluation of prescribing practices: risk of lactic acidosis with metformin therapy. Arch Intern Med 2002; 162: 434–437.
- 22Rojas LB, Gomes MB. Metformin: an old but still the best treatment for type 2 diabetes. Diabetol Metab Syndr 2013; 5: 6.
- 23Gianchandani RY, Pasquel FJ, Rubin DJ, Dungan KM, Vellanki P, Wang H et al. The efficacy and safety of co-administration of sitagliptin with metformin in patients with type 2 diabetes at hospital discharge. Endocr Pract 2018; 24: 556–564.
- 24Salpeter 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; 14: CD002967.
- 25Pasquel FJ, Klein R, Adigweme A, Hinedi Z, Coralli R, Pimentel JL et al. Metformin-associated lactic acidosis. Am J Med Sci 2015; 349: 263–267.
- 26Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005; 366: 1279–1289.
- 27Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M et al. Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 2016; 374: 1321–1331.
- 28Cheng D, Gao H, Li W. Long-term risk of rosiglitazone on cardiovascular events - a systematic review and meta-analysis. Endokrynol Pol 2018; 69: 381–394.
- 29Lee J, Reding M. Effects of thiazolidinediones on stroke recovery: a case-matched controlled study. Neurochem Res 2007; 32: 635–638.
- 30 UK Prospective Diabetes Study (UKPDS) group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837–853.
- 31Rosenstock J, Kahn SE, Johansen OE, Zinman B, Espeland MA, Woerle HJ et al. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. JAMA 2019; 322: 1155–1166.
- 32Tsivgoulis G, Goyal N, Iftikhar S, Zand R, Chang JJ, Elijovich L et al. Sulfonylurea pretreatment and in-hospital use does not impact acute ischemic strokes (AIS) outcomes following intravenous thrombolysis. J Stroke Cerebrovasc Dis 2017; 26: 795–800.
- 33Irvine H, Male S, Robertson J, Bell C, Bentho O, Streib C. Reduced intracerebral hemorrhage and perihematomal edema volumes in diabetics on sulfonylureas. Stroke 2019; 50: 995–998.
- 34Mehta RI, Tosun C, Ivanova S, Tsymbalyuk N, Famakin BM, Kwon MS et al. Sur1-Trpm4 cation channel expression in human cerebral infarcts. J Neuropathol Exp Neurol 2015; 74: 835–849.
- 35Deusenberry CM, Coley KC, Korytkowski MT, Donihi AC. Hypoglycemia in hospitalized patients treated with sulfonylureas. Pharmacotherapy 2012; 32: 613–617.
- 36Rajendran 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.
- 37Pistrosch F, Ganz X, Bornstein SR, Birkenfeld AL, Henkel E, Hanefeld M. Risk of and risk factors for hypoglycemia and associated arrhythmias in patients with type 2 diabetes and cardiovascular disease: a cohort study under real-world conditions. Acta Diabetol 2015; 52: 889–895.
- 38Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013; 369: 1317–1326.
- 39White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013; 369: 1327–1335.
- 40 FDA Drug Safety Communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin. Available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-adds-warnings-about-heart-failure-risk-labels-type-2-diabetes. Last accessed 12 March 2020.
- 41Pasquel 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: 125–133.
- 42Perez-Belmonte LM, Gomez-Doblas JJ, Millan-Gomez 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.
- 43Garg 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.
- 44Chen S, Zhao E, Li W, Wang J. Association between dipeptidyl peptidase-4 inhibitor drugs and risk of acute pancreatitis: A meta-analysis. Medicine (Baltimore) 2017; 96: e8952.
- 45Acharya T, Deedwania P. Cardiovascular outcome trials of the newer anti-diabetic medications. Prog Cardiovasc Dis 2019; 62: 342–348.
- 46Koufakis 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; https://doi.org/10.1111/jcpt.13107.
- 47Sayour AA, Korkmaz-Icöz S, Loganathan S, Ruppert M, Sayour VN, Oláh A et al. Acute canagliflozin treatment protects against in vivo myocardial ischemia-reperfusion injury in non-diabetic male rats and enhances endothelium-dependent vasorelaxation. J Transl Med 2019; 17: 127.
- 48Oshima H, Miki T, Kuno A, Mizuno M, Sato T, Tanno M et al. Empagliflozin, an SGLT2 Inhibitor, Reduced the Mortality Rate after Acute Myocardial Infarction with Modification of Cardiac Metabolomes and Antioxidants in Diabetic Rats. J Pharmacol Exp Ther 2019; 368: 524–534.
- 49Damman K, Beusekamp JC, Boorsma EM, Swart HP, Smilde TDJ, Elvan A et al. Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF). Eur J Heart Fail 2020; 22: 713–722.
- 50Kubota Y, Yamamoto T, Tara S, Tokita Y, Yodogawa K, Iwasaki Y et al. Effect of Empagliflozin Versus Placebo on Cardiac Sympathetic Activity in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Rationale. Diabetes Ther 2018; 9: 2107–2116.
Citing Literature
