Update on the perioperative management of diabetes mellitus

Learning objectivesBy reading this article, you should be able to:•Explain the mechanism of action of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and know the perioperative recommendation.•Outline the indications and beneficial effects of sodium-glucose transporter 2 inhibitors (SGLT2Is) and the main risks of their use in the perioperative period.•Understand the relevant characteristics of different types of diabetes.•Discuss the limitations and concerns for clinicians and the patient on using a continuous glucose monitor (CGM) or continuous subcutaneous insulin infusion (CSII) pump in the perioperative period.Key points•Good preoperative assessment and planning are critical for the optimal perioperative management of diabetes mellitus.•Clinicians must ascertain the type of diabetes in all patients, including children.•Guidelines strongly recommend preoperative HbA1c measurements.•No continuous glucose monitor or continuous subcutaneous insulin infusion pump has been certified for perioperative use.•After surgery, a basal-bolus insulin regimen is preferable to a sliding-scale (short-acting, bolus-only) insulin protocol. By reading this article, you should be able to:•Explain the mechanism of action of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and know the perioperative recommendation.•Outline the indications and beneficial effects of sodium-glucose transporter 2 inhibitors (SGLT2Is) and the main risks of their use in the perioperative period.•Understand the relevant characteristics of different types of diabetes.•Discuss the limitations and concerns for clinicians and the patient on using a continuous glucose monitor (CGM) or continuous subcutaneous insulin infusion (CSII) pump in the perioperative period. •Good preoperative assessment and planning are critical for the optimal perioperative management of diabetes mellitus.•Clinicians must ascertain the type of diabetes in all patients, including children.•Guidelines strongly recommend preoperative HbA1c measurements.•No continuous glucose monitor or continuous subcutaneous insulin infusion pump has been certified for perioperative use.•After surgery, a basal-bolus insulin regimen is preferable to a sliding-scale (short-acting, bolus-only) insulin protocol. Diabetes mellitus is a public health concern, with a steadily increasing global prevalence. According to the International Diabetes Federation (IDF), ∼536 million adults (aged 20–79 yrs) worldwide were living with diabetes in 2019, representing a prevalence of 10.5%.1International Diabetes FederationIDF Diabetes Atlas.10th Edn. IDF, Brussels, Belgium2019Google Scholar Diabetes mellitus is more frequently prevalent in surgical patients compared with the general population, given the increased risk of surgical interventions in individuals with diabetes-related complications, although there are substantial differences between surgical specialties. A meta-analysis of 90 studies, including 866,427 surgical records, reported an overall prevalence of diabetes of 17%.2Martin E.T. Kaye K.S. Knott C. et al.Diabetes and risk of surgical site infection: a systematic review and meta-analysis.Infect Control Hosp Epidemiol. 2016; 37: 88-99Google Scholar The prevalence of diabetes was highest in patients presenting for cardiovascular surgery (up to 39%), followed by orthopaedic surgery.2Martin E.T. Kaye K.S. Knott C. et al.Diabetes and risk of surgical site infection: a systematic review and meta-analysis.Infect Control Hosp Epidemiol. 2016; 37: 88-99Google Scholar Among patients undergoing bariatric surgery, the prevalence of type 2 diabetes was 26%.3Chang S.H. Stoll C.R.T. Song J. Varela J.E. Eagon C.J. Colditz G.A. The effectiveness and risks of bariatric surgery an updated systematic review and meta-analysis, 2003-2012.JAMA Surg. 2014; 149: 275-287Google Scholar The presence of diabetes in surgical patients is associated with an increased risk of perioperative complications, a prolonged hospital stay and higher rates of morbidity and mortality.2Martin E.T. Kaye K.S. Knott C. et al.Diabetes and risk of surgical site infection: a systematic review and meta-analysis.Infect Control Hosp Epidemiol. 2016; 37: 88-99Google Scholar,3Chang S.H. Stoll C.R.T. Song J. Varela J.E. Eagon C.J. Colditz G.A. The effectiveness and risks of bariatric surgery an updated systematic review and meta-analysis, 2003-2012.JAMA Surg. 2014; 149: 275-287Google Scholar Poor glycaemic control in diabetic surgical patients further exacerbates these risks.2Martin E.T. Kaye K.S. Knott C. et al.Diabetes and risk of surgical site infection: a systematic review and meta-analysis.Infect Control Hosp Epidemiol. 2016; 37: 88-99Google Scholar,3Chang S.H. Stoll C.R.T. Song J. Varela J.E. Eagon C.J. Colditz G.A. The effectiveness and risks of bariatric surgery an updated systematic review and meta-analysis, 2003-2012.JAMA Surg. 2014; 149: 275-287Google Scholar Studies have demonstrated a higher incidence of surgical site infections, delayed wound healing, cardiovascular events and respiratory complications in surgical patients with diabetes.2Martin E.T. Kaye K.S. Knott C. et al.Diabetes and risk of surgical site infection: a systematic review and meta-analysis.Infect Control Hosp Epidemiol. 2016; 37: 88-99Google Scholar,3Chang S.H. Stoll C.R.T. Song J. Varela J.E. Eagon C.J. Colditz G.A. The effectiveness and risks of bariatric surgery an updated systematic review and meta-analysis, 2003-2012.JAMA Surg. 2014; 149: 275-287Google Scholar Glucose metabolism plays a vital role in energy production and maintenance of blood glucose concentrations within a narrow range. In healthy individuals, sodium-glucose transporter 1 (SGLT1) and glucose transporter (GLUT) enzymes facilitate glucose uptake in response to oral intake. Furthermore, glucagon-like-peptide-1 (GLP-1) is secreted by the intestinal L-cells in response to eating.4Drucker D.J. Nauck M.A. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes.Lancet. 2006; 368: 1696-1705Google Scholar Binding of GLP-1 to its receptors stimulates insulin secretion from the pancreas. Insulin allows glucose to be transported into the cells, where it undergoes a series of enzymatic reactions, collectively known as glycolysis, to produce energy such as adenosine triphosphate (ATP). Excess glucose is stored in the liver and skeletal muscle as glycogen (glycogenesis). In people with diabetes mellitus, the regulation of glucose metabolism is impaired. The majority of patients presenting with impaired glucose control have type 2 diabetes mellitus (T2DM).5van Wilpe R. Hulst A.H. Siegelaar S.E. DeVries J.H. Preckel B. Hermanides J. Type 1 and other types of diabetes mellitus in the perioperative period. What the anaesthetist should know.J Clin Anesth. 2023; 84111012Google Scholar, 6van Wilpe R. Hulst A.H. Polderman J.A.W. et al.Less common types of diabetes mellitus: incidence and glucose control in the perioperative setting.J Clin Anesth. 2021; 75110460Google Scholar, 7Hulst A.H. Polderman J.A.W. Kooij F.O. et al.Comparison of perioperative glucose regulation in patients with type 1 vs type 2 diabetes mellitus: a retrospective cross-sectional study.Acta Anaesthesiol Scand. 2019; 63: 314-321Google Scholar In T2DM, the body develops insulin resistance, hampering glucose uptake into cells, or the pancreas fails to produce enough insulin to meet the body's demands. Nonetheless, around 10% of adult patients have T1DM or other less common forms of diabetes mellitus. In T1DM, the pancreas fails to produce insulin, which is caused by the (autoimmune) destruction of insulin-producing beta cells in the islets of Langerhans. Besides T1DM and T2DM, many other forms of DM with distinctive pathophysiology exist. Table 1 provides an overview of these different forms of diabetes, with defining characteristics and relevant points for perioperative management.Table 1Types of diabetes and specific concerns for the anaesthetist. CFRD, cystic fibrosis related diabetes; GDM, gestational diabetes mellitus; LADA, latent autoimmune diabetes in adults; MODY, maturity onset diabetes of the young; PTDM, post-transplant DM; T1DM/T2DM, type 1/2 diabetes mellitus.Type of diabetesPathophysiology and clinical featuresInsulin deficiencyPerioperative dysregulationPerioperative concerns1T1DM•Autoimmune destruction of pancreatic β-cells, leading to absolute insulin deficiencyAbsoluteCommon•Hypoglycaemia is common•Consider referral to DM care physician•Always need exogenous insulin source (basal insulin, pump or i.v. drip)2T2DM•Combination of insulin resistance and deficiency caused by diet, life-style and geneticsRelativeDepending on severity•Associated comorbidities•Depending on severityLADA•Autoimmune diabetes which does not manifest until adulthood. Clinically heterogenous group on the continuum between T1DM and T2DMVariableVariable•Do not omit basal insulin, especially if anti-GADi titre is high•Few data regarding perioperative glucose control3aMonogenetic diabetes (e.g. MODY or neonatal diabetes)•Rare forms of diabetes, typically as a result of genetic defects in β-cell function causing impaired insulin secretion. Clinical features depend on the subtype and genetic defectVariableVariable•Clinically heterogenous•MODY subtype 2 (15–50%, Table 2) is generally mild. Manage other types as T1DM or T2DM depending on phenotype3bPancreatic diabetes (e.g. pancreatitis) CFRD•Pancreatitis leads to islet tissue fibrosis and destruction, resulting in insulin and glucagon deficiency.VariableYes•Marked glycaemic variability and possibly unpredictable response to exogenous insulin3cEndocrinopathy-related DM•Insulin resistance and deficiency as a result of the excess release of counterregulatory hormones such as cortisol, GH/IGF-1 and catecholaminesLimitedYes•Commonly requires glycaemic monitoring and insulin (especially for phaeochromocytoma)•Beware of rebound hypoglycaemia after tumour resection3dMedication- related DM (e.g. glucocorticoid- induced) and PTDM•Systemic corticosteroid treatment causes insulin resistance, increased gluconeogenesis and abnormal insulin secretion•PTDM is primarily caused by diabetogenic properties of the immunosuppressive agentsLimitedNo•Corticosteroid stress doses cause hyperglycaemia•Hyperglycaemia in PTDM is associated with risk of transplant rejection4GDM•Diabetes first diagnosed during pregnancy. Associated with an increased risk of developing T2DM in later lifeLimitedNo•Perioperative glycaemic target: 3.9–8.0 mmol L−1, as glucose ≥8.0 mmol L−1 may cause transient neonatal hyperinsulinism and neonatal hypoglycaemia Open table in a new tab Diabetes mellitus is also one of the most common chronic diseases in children, and the incidences of both T1DM and T2DM in children are increasing. This is partly triggered by the increasing incidence of obesity in childhood. Currently, 20–40% of the patients with newly diagnosed T1DM are obese.8Lawrence J.M. Divers J. Isom S. et al.Trends in prevalence of type 1 and type 2 diabetes in children and adolescents in the US, 2001-2017.JAMA. 2021; 326: 717-727Google Scholar The relation between obesity and T2DM is well established. Historically, T2DM accounted for 10% of paediatric patients; today, T2DM already accounts for >30% of paediatric patients in the USA.8Lawrence J.M. Divers J. Isom S. et al.Trends in prevalence of type 1 and type 2 diabetes in children and adolescents in the US, 2001-2017.JAMA. 2021; 326: 717-727Google Scholar Although the number of patients with T1DM is increasing, the prevalence of children with T2DM has increased even more in the last two decades.8Lawrence J.M. Divers J. Isom S. et al.Trends in prevalence of type 1 and type 2 diabetes in children and adolescents in the US, 2001-2017.JAMA. 2021; 326: 717-727Google Scholar Furthermore, obesity in children with impaired insulin secretion will lead to an earlier clinical manifestation of T1DM. Insulin needs are unmet because of obesity-induced insulin resistance, and obesity influences the progression of islet autoimmunity. This means that a child with DM will not necessarily have T1DM, and a child with obesity and DM will not necessarily have T2DM. Therefore, it is vital to pay close attention to the type of diabetes in children and adults, because requirements and management differ between types of diabetes (Table 1). One of the most important parts of perioperative care for patients with DM is a thorough preoperative assessment, including the adjustments to medication and a plan for in-hospital glucose control. A perioperative pathway for people with diabetes has the potential to increase efficiency and reduce waiting lists for elective surgery.9Rayman G. Page E. Hodgson S. Henley W. Wr Briggs T. Gray W.K. Improving the outcomes for people with diabetes undergoing surgery: an observational study of the Improving the Peri-operative Pathway of People with Diabetes (IP3D) intervention.Diabetes Res Clin Pract. 2024; 207111062Google Scholar Before surgery, we should focus on the assessment of the type of DM, antihyperglycaemic treatment, quality of glycaemic control and the severity of the diabetes-related complications such as cardiovascular disease, chronic renal failure, autonomic dysfunction and delayed gastric emptying. Secondary goals include optimising glycaemic control and general prehabilitation because of the increased risk profile of patients with DM. Patients have a higher prevalence of (advanced) coronary artery disease, increasing their risk of postoperative myocardial (silent) ischaemia and perioperative mortality after non-cardiac surgery (NCS).10Halvorsen S. Mehilli J. Cassese S. et al.2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery.Eur Heart J. 2022; 43: 3826-3924Google Scholar In addition, DM-induced autonomic dysfunction and peripheral neuropathy increase the risk of silent ischaemia.11Kadoi Y. Anesthetic considerations in diabetic patients. Part II: intraoperative and postoperative management of patients with diabetes mellitus.J Anesth. 2010; 24: 748-756Google Scholar Furthermore, diabetes is a risk factor for stroke, congestive heart failure and surgical site infections. People with diabetes are considered good candidates for prehabilitation programmes because the commonly included diet and exercise interventions can improve glycaemic control and general health.12Laza-Cagigas R. Chan S. Sumner D. Rampal T. Effects and feasibility of a prehabilitation programme incorporating a low-carbohydrate, high-fat dietary approach in patients with type 2 diabetes: a retrospective study.Diabetes Metab Syndr. 2020; 14: 257-263Google Scholar In 2022, the European Society of Cardiology (ESC) published an update of their guideline for the assessment and management of patients undergoing NCS.10Halvorsen S. Mehilli J. Cassese S. et al.2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery.Eur Heart J. 2022; 43: 3826-3924Google Scholar This guideline includes two recommendations regarding diabetes and haemoglobin A1c (HbA1c).(i)'In patients at high surgical risk, clinicians should consider screening for increased HbA1c before major surgery and improving preoperative glucose control.' (recommendation class: IIa)10Halvorsen S. Mehilli J. Cassese S. et al.2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery.Eur Heart J. 2022; 43: 3826-3924Google Scholar However, screening for unknown diabetes mellitus through HbA1c measurements is not further substantiated, while the probability of diagnosing unknown diabetes is likely to depend on many factors. The incidence of undiagnosed diabetes differs significantly between regions or countries and is associated with income, resources, national guidelines and the quality of the (primary) healthcare system. This influences the cost-effectiveness of screening and should be implemented after such factors have been considered.(ii)'In patients with diabetes or disturbed glucose metabolism, a preoperative HbA1c test is recommended if this measurement has not been performed in the previous three months. In case of HbA1c ≥8.5% (≥69 mmol mol−1), elective NCS should be postponed if safe and practical.' (recommendation class: I)10Halvorsen S. Mehilli J. Cassese S. et al.2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery.Eur Heart J. 2022; 43: 3826-3924Google Scholar The available evidence for this strong recommendation by the ESC guideline is also poor. This is probably because the differentiation between association and causation has often been unclear. Factors extensively documented as independently associated with postoperative complications and worse outcomes include diabetes mellitus, increased preoperative HbA1c and perioperative hyperglycaemia. However, optimising preoperative glucose control in patients with a high HbA1c has not been studied in randomised controlled trials, and it is debatable whether this would prove an effective intervention. Nonetheless, HbA1c measurements provide valuable information on long-term glycaemic control in the previous months. Figure 1 provides an interpretation of HbA1c values. We support improving HbA1c concentrations in every patient, but are wary of the possible consequences before surgery. The COVID-19 pandemic demonstrated that postponement of surgery can seriously affect patients' health and quality of life.13EditorialToo long to wait: the impact of COVID-19 on elective surgery.Lancet Rheumatol. 2021; 3: e83Google Scholar Therefore, the lack of evidence on preoperative HbA1c lowering should be weighed against the negative impact on patient satisfaction, health and quality of care when considering postponing surgery based on HbA1c concentrations. In addition to established medications such as metformin and sulfonylurea derivates, two newer non-insulin glucose-lowering drugs have been introduced and are gaining popularity. The mechanism of action of both GLP-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors (SGLT2Is) are discussed below. A summary of the relevant US/UK guidelines on perioperative management of the most common non-insulin glucose-lowering medications is provided in Table 2.14Elsayed N.A. Aleppo G. Aroda V.R. et al.16. Diabetes care in the hospital: standards of care in diabetes—2023.Diabetes Care. 2023; 46: S267-S278Google Scholar,15Ayman G. Dhatariya K. Dhesi J. et al.Guideline for Perioperative Care for People with Diabetes Mellitus Undergoing Elective and Emergency Surgery. Centre for Perioperative Care, 2021https://cpoc.org.uk/guidelines-resources-guidelines-resources/guideline-diabetesDate accessed: March 27, 2024Google ScholarTable 2Guidelines on perioperative management of the most commonly used non-insulin glucose-lowering medications. ∗If contrast medium is to be used and eGFR <60 ml min−1 1.73 m−2, metformin should be omitted on the day of the procedure and for the following 48 h. ADA, American Diabetes Association Guideline Jan 2024; CPOC, Centre for perioperative Care, Academy of Medical Royal Colleges, Dec 2022.Medication class (example)Mechanism of actionPerioperative concernsPerioperative managementBiguanides (metformin)Decreases hepatic glucose production and increases muscle glucose absorption(Lactic acidosis)ADA: omit on day of surgery until oral intake resumedCPOC: continue∗Sulfonylureas (tolbutamide, glibenclamide, glimepiride)Stimulates β cell insulin secretionHypoglycaemiaADA and CPOC: withhold on the day of surgery until oral intake resumedThiazolidinediones (glitazones)Decreases insulin resistanceFluid retention; hypoglycaemiaADA: withhold on the day of surgery until oral intake resumedCPOC: continueGlucagon-like peptide-1 receptor agonists (GLP-1 RAs)('-natides', '-glutides')Stimulates insulin secretion and inhibits glucagon secretion, glucose-dependentDelayed gastric emptyingADA: withhold on the day of surgery until oral intake resumedCPOC: continueDipeptidyl protein-4 inhibitors (DPP-4i)'-gliptins')Increases GLP-1 concentrationsADA: withhold on the day of surgery until oral intake resumedCPOC: continueSodium-glucose transport-2 inhibitors (SGLT2Is) ('-gliflozins')Induces renal glucose excretionEuglycaemic ketoacidosis, diuresis, hypoglycaemia with insulinADA: withhold 72–96 h before surgeryCPOC: withhold 48 h before surgery Open table in a new tab Endogenous GLP-1 is a gut-derived incretin hormone that reduces glycaemia by stimulating insulin production and secretion from pancreatic β cells and by reducing glucagon secretion from α cells. In addition, GLP-1 inhibits gastric emptying and reduces appetite. Although this leads to less food intake, weight loss and improved glycaemic control, it is also responsible for the main adverse effect of nausea. Notably, the pancreatic effects of GLP-1 are hyperglycaemia-dependent, making the risk for hypoglycaemia extremely low. Besides established efficacy in glycaemic control, enthusiasm for these medications increased with the findings of large cardiovascular outcome trials that found clear benefits of lower rates of myocardial infarction, stroke and revascularisation procedures. Initially, GLP-1 RAs came to the market as a second-line treatment option for T2DM, but currently, the indications are expanding to include weight loss in patients with obesity (regardless of T2DM). This field is rapidly developing with the introduction of dual and triple agonists (for a combination of GLP-1, GLP-2, glucagon and GIP [gastric inhibitory peptide]). The number of patients using a form of GLP-1 RAs is expected to increase significantly in the coming years, given the beneficial effects on diabetes-related complications and the expansion of the indication to weight control. Initially, withholding GLP-1 RAs was advised for in-hospital patients, whereas others are considering perioperative continuation, given the low risk of hypoglycaemia and improved glycaemic control,14Elsayed N.A. Aleppo G. Aroda V.R. et al.16. Diabetes care in the hospital: standards of care in diabetes—2023.Diabetes Care. 2023; 46: S267-S278Google Scholar,16Hulst A.H. Plummer M.P. DeVries J.H. Deane A.M. Preckel B. Hermanides J. Incretins and the anaesthetist: a systematic review.Eur J Anaesthesiol. 2018; 35: 55-56Google Scholar,17Hulst A.H. Visscher M.J. Godfried M.B. et al.Liraglutide for perioperative management of hyperglycaemia in cardiac surgery patients: a multicentre randomized superiority trial.Diabetes Obes Metab. 2020; 22: 557-565Google Scholar also because the advent of longer-acting (once-weekly) preparations makes adequate withholding more impractical.18Hulst A.H. Polderman J.A.W. Siegelaar S.E. et al.Preoperative considerations of new long-acting glucagon-like peptide-1 receptor agonists in diabetes mellitus.Br J Anaesth. 2021; 126: 567-571Google Scholar,19van Zuylen M.L. Siegelaar S.E. Plummer M.P. Deane A.M. Hermanides J. Hulst A.H. Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration.Br J Anaesth. 2024; 132: 644-648Google Scholar Drugs from this medication class all end with –natides or –glutides. The primary (adverse) effect of delayed gastric emptying raises concerns from anaesthetists because of the potential risk of aspiration and postoperative nausea and vomiting (PONV). Although GLP-1 RAs delay gastric emptying, this is most notable for the first postprandial hours and subsides as a result of tolerance and tachyphylaxis with ongoing treatment.19van Zuylen M.L. Siegelaar S.E. Plummer M.P. Deane A.M. Hermanides J. Hulst A.H. Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration.Br J Anaesth. 2024; 132: 644-648Google Scholar,20Hjerpsted J.B. Flint A. Brooks A. Axelsen M.B. Kvist T. Blundell J. Semaglutide improves postprandial glucose and lipid metabolism, and delays first-hour gastric emptying in subjects with obesity.Diabetes Obes Metab. 2018; 20: 610-619Google Scholar Therefore, caution is needed about delayed gastric emptying in patients recently started on a GLP-1 RA, although after >12 weeks of treatment and after standard preoperative fasting times, gastric emptying is probably normal.19van Zuylen M.L. Siegelaar S.E. Plummer M.P. Deane A.M. Hermanides J. Hulst A.H. Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration.Br J Anaesth. 2024; 132: 644-648Google Scholar,20Hjerpsted J.B. Flint A. Brooks A. Axelsen M.B. Kvist T. Blundell J. Semaglutide improves postprandial glucose and lipid metabolism, and delays first-hour gastric emptying in subjects with obesity.Diabetes Obes Metab. 2018; 20: 610-619Google Scholar Although SGLT2Is initially proved moderately effective in improving glycaemic control, subsequent large cardiovascular outcome trials in people with T2DM demonstrated that SGLT2Is improved major cardiorenal outcomes.21Hulst A.H. Hermanides J. DeVries J.H. Preckel B. Potential benefits of sodium-glucose cotransporter-2 inhibitors in the perioperative period.Anesth Analg. 2018; 127: 306-307Google Scholar Treatment with SGLT2Is reduces hospitalisation rates for heart failure and the progression of chronic kidney disease.22McDonagh T.A. Metra M. Adamo M. et al.2023 Focused update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure.Eur Heart J. 2023; 44: 3627-3639Google Scholar,23Mark P.B. Sarafidis P. Ekart R. et al.SGLT2i for evidence-based cardiorenal protection in diabetic and non-diabetic chronic kidney disease: a comprehensive review by EURECA-m and ERBP working groups of ERA.Nephrol Dial Transplant. 2023; 38: 2444-2455Google Scholar Given the moderate improvements in HbA1c, the mechanisms of action on the heart and kidney are unlikely to be mediated by glucose control alone. Large randomised clinical trials in patients with heart failure (with preserved and reduced ejection fraction) and chronic kidney disease, all irrespective of a history of diabetes, demonstrated improved outcomes.22McDonagh T.A. Metra M. Adamo M. et al.2023 Focused update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure.Eur Heart J. 2023; 44: 3627-3639Google Scholar,23Mark P.B. Sarafidis P. Ekart R. et al.SGLT2i for evidence-based cardiorenal protection in diabetic and non-diabetic chronic kidney disease: a comprehensive review by EURECA-m and ERBP working groups of ERA.Nephrol Dial Transplant. 2023; 38: 2444-2455Google Scholar Indications are expanding from T2DM to patients with heart failure and chronic kidney disease without DM.22McDonagh T.A. Metra M. Adamo M. et al.2023 Focused update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure.Eur Heart J. 2023; 44: 3627-3639Google Scholar,23Mark P.B. Sarafidis P. Ekart R. et al.SGLT2i for evidence-based cardiorenal protection in diabetic and non-diabetic chronic kidney disease: a comprehensive review by EURECA-m and ERBP working groups of ERA.Nephrol Dial Transplant. 2023; 38: 2444-2455Google Scholar Although rare, the primary concern with SGLT2Is in the perioperative period is their association with euglycaemic ketoacidosis. This is an incompletely understood complication of using SGLT2Is, possibly precipitated by the surgical stress response. A retrospective review of 1307 patients on SGLT2Is undergoing surgical procedures found a euglycaemic diabetic ketoacidosis (DKA) incidence of 0.2% in non-emergent procedures and 1.1% for emergent procedures, given the inability to withhold SGLT2is in the latter group.24Mehta P.B. Robinson A. Burkhardt D. Rushakoff R.J. Inpatient perioperative euglycemic diabetic ketoacidosis due to sodium-glucose cotransporter-2 inhibitors – lessons from a case series and strategies to decrease incidence.Endocr Pract. 2022; 28: 884-888Google Scholar Expert opinion and guidelines recommend withholding SGLT2Is perioperatively, although the recommended durations vary. The Centre for Perioperative Care (CPOC) recommends omission from the before surgery, whereas the ESC recommends 3 days before surgery.10Halvorsen S. Mehilli J. Cassese S. et al.2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery.Eur Heart J. 2022; 43: 3826-3924Google Scholar,15Ayman G. Dhatariya K. Dhesi J. et al.Guideline for Perioperative Care for People with Diabetes Mellitus Undergoing Elective and Emergency Surgery. Centre for Perioperative Care, 2021https://cpoc.org.uk/guidelines-resources-guidelines-resources/guideline-diabetesDate accessed: March 27, 2024Google Scholar Drugs from this medication class all end with –gliflozins. Several studies are underway to assess starting an SGLT2I before surgery to prevent acute kidney injury (NCT05590143). Insulin is prescribed in different forms of preparations and dosing schemes. Available insulin preparations differ little pharmacodynamically but mostly in pharmacokinetics, ranging from (ultra-) short-acting to long-acting and mixed preparations, requiring between one to several injections daily or a continuous infusion via an insulin pump. The literature provides many recommendations on dose adjustments in the perioperative period. In clinical practice, we recommend adherence to one's institutional protocol for the perioperative treatment of diabetes, even though local protocols cause significant variability between hospitals, deviating from international guidelines.25Hulst A.H. Hermanides J. DeVries J.H. Preckel B. Current perioperative manageme