New Canadian guideline for using GLP-1 agonists and SGLT2 inhibitors for cardiorenal risk reduction

The Canadian Cardiovascular Society (CCS) has developed a new guideline for the use of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors for cardiorenal risk reduction in adults. The CCS recognizes that the opportunity to help reduce cardiorenal morbidity and mortality through the use of diabetes-related drugs requires vigilance in identifying appropriate patients for therapy. Therefore, as part of a comprehensive cardiovascular (CV) risk assessment, CV specialists are encouraged to assess kidney and glycemic status through measurement of estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (UACR) and glycated hemoglobin (A1C), and to document left ventricular ejection fraction (LVEF) when evaluating symptoms of heart failure (HF). Read: Eating within a 10-hour window beneficial to type 2 diabetes The guideline includes a table that summarizes the relative benefits (hazard ratios) and event reductions per 1,000 patients treated with SGLT2 inhibitors or GLP-1 receptor agonists for cardiorenal outcomes in study populations with heart failure, chronic kidney disease or type 2 diabetes. Another table summarizes the SGLT2 inhibitors and GLP-1 receptor agonists associated with statistically significant cardiorenal outcome reductions in major randomized clinical trials. Guideline recommendations: Treatment of HF In adults with HF and LVEF ≤ 40%, the use of SGLT2 inhibitors is recommended to reduce all-cause and CV mortality, hospitalization for HF, and the composite end point of significant decline in eGFR, progression to end-stage kidney disease or death due to kidney disease (strong recommendation; moderate quality of evidence). In adults with HF and LVEF > 40%, use of SGLT2 inhibitors is recommended to reduce hospitalization for HF (strong recommendation; moderate quality of evidence). Treatment of CKD In adults with CKD (UACR > 20 mg/mmol, eGFR ≥ 25 mL/min/1.73m2), the use of SGLT2 inhibitors is recommended to reduce the composite of significant decline in eGFR, progression to end-stage kidney disease or death due to kidney disease, all-cause and CV mortality, nonfatal myocardial infarction and hospitalization for HF (strong recommendation; moderate quality of evidence). Prevention of cardiorenal events In adults with type 2 diabetes and either ASCVD or multiple risk factors for ASCVD, use of the following is recommended (all are strong recommendations, with moderate quality of evidence): GLP-1 receptor agonist or SGLT2 inhibitor to reduce the risk of all-cause or CV mortality or major adverse cardiac events (MACE) SGLT2 inhibitor to reduce the risk of hospitalization for HF or the composite of significant decline in eGFR, progression to end-stage kidney disease or death due to kidney disease GLP-1 receptor agonist to reduce the risk of nonfatal stroke. Practical considerations The guideline addresses practical considerations for integrating GLP-1 receptor agonists and SGLT2 inhibitors into cardiovascular practice, including a summary algorithm. A separate algorithm assists with management of antihyperglycemic medications when adding a SGLT2 inhibitor (eGFR ≥ 45 mL/min/1.73 m2) or GLP-1 receptor agonist. Two additional figures summarize contraindications, cautions, starting doses, special considerations and follow-up requirements for each drug class. A helpful table lists potential side effects of GLP-1 receptor agonists and SGLT2 inhibitors and strategies to minimize them. Summary The guideline stresses that the profound benefits of GLP-1 receptor agonists and SGLT2 inhibitors in the treatment of established HF or CKD or in the prevention of cardiorenal morbidity or mortality are not strongly tied to A1C-lowering. Therefore, starting these agents should not be based on the need for additional A1C-lowering. Determining the suitability of GLP-1 receptor agonist and SGLT2 inhibitor use for cardiorenal protection will require shared decision-making with patients and interdisciplinary collaboration among cardiologists, nephrologists, endocrinologists, primary care physicians and pharmacists. Healthcare providers should make every effort to integrate these diabetes-related agents with cardiorenal benefits into overall and individualized treatment plans. Read: Is type 2 diabetes becoming an obsolete diagnosis? Reference 1. Mancini GBJ, O’Meara E, Zieroth S, et al. Canadian Cardiovascular Society guideline for use of GLP-1 receptor agonists and SGLT2 inhibitors for cardiorenal risk reduction in adults. Can J Cardiol 2022;38:1153-67. (accessed August 30, 2022)

New Canadian guideline for using GLP-1 agonists and SGLT2 inhibitors for cardiorenal risk reduction

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