Preoperative considerations of new long-acting glucagon-like peptide-1 receptor agonists in diabetes mellitus

The current preoperative recommendation for the inpatient population regarding use of non-insulin glucose-lowering treatment is to withhold this medication on day surgery.1American Diabetes AssociationDiabetes care in hospital.Diabetes Care. 2018; 41: S144-S151Crossref PubMed Scopus (124) Google Scholar,2Dhatariya K. Levy N. Kilvert A. et al.NHS guideline perioperative management adult patient with diabetes.Diabet Med. 2012; 29: 420-433Crossref (173) Scholar reasons are variable different preparations and involve risks hypoglycaemia, lactic acidosis, keto-acidosis.3Thiruvenkatarajan V. Meyer E.J. Nanjappa Van Wijk R.M. Jesudason D. Perioperative diabetic ketoacidosis associated sodium-glucose co-transporter-2 inhibitors: a systematic review.Br J Anaesth. 2019; 123: 27-36Abstract Full Text PDF (39) Until recently, all these drugs had short half-lives, were taken once or multiple times daily, eliminated from body within 1 day. This enabled one-size-fits-all that now well-known followed.4Hulst A.H. Hermanides J. Hollmann M.W. DeVries J.H. Preckel B. Lack consensus peri-operative patients diabetes mellitus.Eur Anaesthesiol. 36: 168-169Crossref (4) However, recent advances include once-weekly long-acting glucagon-like peptide-1 receptor agonists (GLP-1 RAs). prompts anaesthesiologists reconsider their practice stopping antidiabetic medications morning surgery. We argue benefits continuation outweigh risk withholding medications, therefore propose non-withholding policy GLP-1 RAs. focus new class RAs (named -natide -glutide, e.g. exenatide/liraglutide), not be confused recently introduced sodium glucose inhibitors (names ending -gliflozin, empagliflozin). Although cardio-reno-protective properties might harbour potential,5Hulst Potential cotransporter-2 period.Anesth Analg. 127: 306-307Crossref (1) they generally recommended withheld before surgery, until more data safety known.6Bardia Wai M. Fontes M.L. Sodium-glucose an overview implications.Curr Opin 32: 80-85Crossref (15) Endogenous gut-derived incretin hormone reduces glycaemia by stimulating insulin production secretion pancreatic beta cells reducing glucagon alpha cells.7Drucker D.J. Nauck M.A. system: dipeptidyl peptidase-4 type 2 diabetes.Lancet. 2006; 368: 1696-1705Abstract (2904) In addition, inhibits gastric emptying, appetite food intake which contribute lowering.7Drucker Scholar,8Meier J.J. individualized mellitus.Nat Rev Endocrinol. 8: 728-742Crossref (749) Importantly, effects only operate during hyperglycaemia, making hypoglycaemia extremely low.7Drucker has half-life several minutes rapidly broken down (DPP-4). first generation (e.g. exenatide, lixisenatide) designed resist DPP-4-breakdown could administered either twice daily.8Meier Second-generation liraglutide, dulaglutide) have higher protein-binding, thereby renal clearance, further prolonging half-life.8Meier last decade, came market as second-line option mellitus.7Drucker Besides established efficacy improving control, enthusiasm increased findings large cardiovascular outcome trials.9Pfeffer Claggett Diaz R. al.Lixisenatide acute coronary syndrome.N Engl 2015; 373: 2247-2257Crossref (1413) Scholar, 10Marso S.P. Daniels G.H. Brown-Frandsen al.Liraglutide outcomes diabetes.N 2016; 375: 311-322Crossref (3598) 11Marso Bain S.C. Consoli al.Semaglutide 1834-1844Crossref (2459) 12Holman R.R. Bethel Mentz R.J. al.Effects exenatide 2017; 377: 1228-1239Crossref (968) 13Hernandez A.F. Green J.B. Janmohamed S. al.Albiglutide disease (Harmony Outcomes): double-blind, randomised placebo-controlled trial.Lancet. 392: 1519-1529Abstract (716) 14Gerstein H.C. Colhoun H.M. Dagenais G.R. al.Dulaglutide (REWIND): 394: 121-130Abstract (848) long-term trials prove safety. All confirmed safe did increase major adverse events (MACE).15Holst Long-acting agonist – status December 2018.Ann Transl 7 (83–3)Crossref What was even important reports studies actually showed reduction MACE compared standard treatment. currently available preparations, characteristics, most respective summarised Table 1.Table 1Overview agonists. ∗For superiority. †Originally once-daily formulation, prolonged release injection once-weekly. CI, confidence interval; HR, hazard ratio.Duration actionEffectivenessReferenceDrugHalf-lifeDosing frequencyHbA1c lowering mmol mol−1Major (MACE)Cardiovascular trialLixisenatide2.5 hDaily 10–20 μg3 (2–3)Non-inferior placebo (HR=1.02, 95% CI=0.89–1.17, P=0.81∗)ELIXA8Meier ScholarExenatide3 hTwice daily 5–10 μg/weekly mg†8 (7–8)Non-inferior (HR=0.91, CI=0.83–1.00, P=0.06∗)EXSCEL11Marso ScholarLiraglutide12.5 1.8 mg5 (4–5)Superior (HR=0.87, CI=0.78–0.97, P=0.01∗)LEADER9Pfeffer ScholarAlbiglutide5 daysWeekly 30–50 mg8 (7–8)Superior (HR=0.78, CI=0.68–0.90, P=0.006∗)HARMONY12Holman ScholarDulaglutide5 1.5 mg7 (6–7)Superior (HR=0.88, CI=0.79–0.99, P=0.026∗)REWIND13Hernandez ScholarSemaglutide7 0.5–1.0 mg11 (10–12)Superior (HR=0.74, CI=0.58–0.95, P=0.02∗)SUSTAIN-610Marso Open table tab observed cardioprotective resulted extensive research physiology, many postulated mechanisms.16Giblett J.P. Clarke S.J. Dutka D.P. Hoole Glucagon-like peptide-1: promising agent cardioprotection myocardial ischemia.JACC Basic Sci. 1: 267-276Crossref (17) consistently reported finding expression receptors sinoatrial node.15Holst explains HR found administering RAs, it unlikely explanation any properties.15Holst Scholar,17Hulst Visscher M.J. Cherpanath T.G.V. liraglutide function after cardiac surgery: secondary analysis controlled GLOBE trial.J Clin 2020; 9: 673Crossref (3) Thus far, mechanisms poorly understood. Animal increases metabolic efficiency usage, lower vascular resistances pulmonary systemic circulations, activation ischaemic preconditioning pathways.16Giblett humans, relevance remains unclear, despite some results improved left ventricular reduced infarct size injury RA-treated subjects.18Nikolaidis L.A. Mankad Sokos G.G. infarction dysfunction successful reperfusion.Circulation. 2004; 109: 962-965Crossref (745) Scholar,19Read P.A. Khan F.Z. Cardioprotection against ischaemia induced dobutamine stress using artery disease.Heart. 98: 408-413Crossref (86) remains, however, (Table 1) clear rates infarction, stroke, revascularisation procedures.10Marso Scholar,11Marso Scholar,13Hernandez Scholar,14Gerstein commonly side-effects gastrointestinal, such nausea, vomiting, diarrhoea.7Drucker SUSTAIN trial, 52% gastrointestinal those receiving semaglutide 35% group, resulting discontinuation 14% 8% patients, respectively.11Marso Nausea vomiting explained direct central delayed emptying. Both decrease over time ongoing because tolerance tachyphylaxis.8Meier Scholar,20Deane A.M. Chapman Fraser al.The effect exogenous glycaemic response small intestinal nutrient critically ill: double-blind cross study.Crit 2009; 13: R67Crossref (68) 21Plummer M.P. Jones K.L. Annink C.E. al.Glucagon-like peptide attenuates acceleration emptying hypoglycemia healthy subjects.Diabetes 2014; 37: 1509-1515Crossref (27) 22Umapathysivam M.M. Lee M.Y. al.Comparative intermittent stimulation glycemia.Diabetes. 63: 785-790Crossref (83) 23Meier Rosenstock Hincelin-Méry al.Contrasting lixisenatide postprandial glycemic parameters optimized glargine without metformin: randomized, open-label trial.Diabetes 38: 1263-1273Crossref (176) 24Nauck Kemmeries G. Holst Meier Rapid tachyphylaxis 1-induced deceleration humans.Diabetes. 2011; 60: 1561-1565Crossref (241) After 8 weeks (a RA), returned near baseline values.23Meier Of note, contrasting been shorter acting retained time.23Meier oral beneficial loss weight overweight obese worry given theoretically aspiration. although symptoms mostly mild, rarely reason therapy, seem treatment.7Drucker Scholar,25Nauck Hompesch Filipczak al.Five analogue improves control lowers subjects diabetes.Exp Endocrinol Diabetes. 114: 417-423Crossref (138) 26Lean M.E. Carraro Finer al.Tolerability nausea associations randomized trial obese, non-diabetic adults.Int Obes. 689-697Crossref (114) 27Kendall D.M. Riddle M.C. (exendin-4) 30 treated metformin sulfonylurea.Diabetes 2005; 28: 1083-1091Crossref (1075) occurred trials, initiation led 1–3% cases.10Marso On ICU, also motility, its minimal when already delayed.28Deane absorption relationship glycemia.Crit Care 2010; 1261-1269Crossref (76) mellitus, gastroparesis known complication requires attention appropriate action anaesthesiologists. Postoperatively, upset common concern. Despite fact surprisingly few recorded outcome,29Hulst Plummer al.Systematic review therapy intensive care.Crit 22: 1-12Crossref (11) reassuring do appear postoperative vomiting.30Polderman J.A.W. van Steen S.C.J. Thiel al.Peri-operative type-2 mellitus undergoing non-cardiac surgery glucose–insulin–potassium infusion intravenous bolus regimens: trial.Anaesthesia. 73: 332-339Crossref (21) 31Hulst Godfried M.B. hyperglycaemia patients: multicentre superiority Obes Metab. 557-565Crossref (9) 32Besch Perrotti Mauny F. al.Clinical effectiveness bypass graft surgery.Anesthesiology. 775-787Crossref (16) performed two studying administration, including than 400 patients. both intervention group report non-GLP-1 groups, neither nor Several investigated period, showing control.29Hulst used continuous grafting (CABG) concentrations.33Sokos Bolukoglu H. German al.Effect (GLP-1) grafting.Am Cardiol. 2007; 100: 824-829Abstract (209) Scholar,34Kohl B.A. Hammond M.S. Cucchiara A.J. Ochroch E.A. Intravenous (7-36) amide prevention hyperglycemia study.J Cardiothorac Vasc Anesth. 618-625Abstract A i.v. (first generation, short-acting RA) CABG blood concentrations requirements, surgery.32Besch Scholar,35Lipš Mráz Kloučková single-blind, 19: 1818-1822Crossref (13) approved s.c. administration. Liraglutide (second effective requirements noncardiac surgery.30Polderman Scholar,31Hulst studies, outcomes, yet no signal harm detected. meta-analysis increasing incidence hypoglycaemia.29Hulst specific situations, taking should considered. Post-marketing surveillance possible association between pancreatitis cancer. large-scale pancreas pathology. Nonetheless, must Furthermore, impaired kidney function, stopped case requiring replacement therapy. Finally, we suggest ileus though problem abates time. No study RA, at least one underway dulaglutide (NCT 03743025). growing. As result, will increasingly encounter With introduction newer once-weekly, advice antihyperglycaemic preoperatively needs reconsidered. Firstly, stop impractical. Effective would require ≥2 advance, affecting similar period. often seen shortly lead unnecessary postponement worse complications.36Iavazzo C. McComiskey Datta al.Preoperative HBA1c complications gynaecological cancer.Arch Gynecol Obstet. 294: 161-164Crossref (12) Scholar,37Kotagal Symons R.G. Hirsch I.B. al.Perioperative among diabetes.Ann Surg. 261: 97-103Crossref (182) Secondly, perioperatively likely practice. hypoglycaemia. Few mild. aware theoretical can considered shorter-acting withheld, recommend continuing throughout line Association Anaesthetists day-case surgery,38Bailey C.R. Ahuja Bartholomew al.Guidelines 2019: guidelines British surgery.Anaesthesia. 74: 778-792Crossref (60) extend ambulatory Experts highlighted potentially advantageous aspects in-hospital hyperglycaemia,39Umpierrez G.E. Korytkowski Is incretin-based ready hospitalized diabetes?.Diabetes 2013; 2112-2117Crossref (36) Scholar,40Mustafa O.G. Whyte hospitalised untapped potential.Diabetes Metab Res Rev. 35e3191Crossref shown adjunct control.30Polderman Scholar,41Fayfman Galindo Rubin al.A general medicine diabetes.Diabetes 42: 450-456Crossref (26) arguments continuation, hospital stay better period developing Side-effects, frequently nature, mild diminish Historically, weekly preoperatively. impractical but inadequate light evidence, regard side-effects. continued