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The Canadian cardiovascular community has encouraged cardiorenal risk reduction with glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) for patients with type 2 diabetes (T2D) who have or are at risk of cardiovascular (CV) disease.[1],[2] However, to date, no formal guideline has been published by the Canadian Cardiovascular Society (CCS) regarding the use of these agents. Moreover, the application of SGLT2i has expanded beyond management of T2D to include the treatment of heart failure (HF) and chronic kidney disease (CKD) in individuals with and without diabetes. The purpose of this guideline is to assist CV practitioners in the safe and effective use of these 2 drug classes while building upon and remaining concordant with the most recent, high-quality guidelines published by Diabetes Canada,[3],[4] the CCS/Canadian Heart Failure Society (CHFS),[5] and the Kidney Disease Improving Global Outcomes (KDIGO).6 Although complex patients are best managed by a shared care model, this guideline is also intended to help any CV specialist identify situations when a more proactive or even lead role might be warranted when simple and safe implementation is quite feasible. The reader is advised to consider the specialty guidelines for comprehensive diagnosis and management of patients with T2D, HF, or CKD, including management of glycosylated hemoglobin (A1c). The recommendations in this guideline are specifically intended for cardiorenal risk reduction. Treatment recommendations for symptomatic hyperglycemia, metabolically decompensated patients with T2D, patients with type 1 diabetes, patients receiving dialysis or with severely compromised renal function (estimated glomerular filtration rate [eGFR] < 20 mL/min/1.73 m2), or patients with acutely decompensated HF or CKD are beyond the scope of this guideline.

We assembled a panel of content and methods experts with representation from key Canadian partner organizations including Diabetes Canada, the CHFS, and the Canadian Society of Nephrology, drawing from community and academic practice settings, with broad geographic representation and considering equity and diversity. We conducted a de novo systematic review and meta-analysis on the basis of a series of focused Population, Intervention, Comparison, Outcome (PICO) questions in which the interventions were SGLT2i and GLP-1RA, and in which the comparator was standard care. The meta-analysis was specifically commissioned by the CCS to support this guideline.[7] This guideline focused on the critical outcomes of total mortality, CV mortality, nonfatal myocardial infarction (MI), nonfatal stroke, major adverse cardiac events (MACE: CV death, nonfatal MI, or nonfatal stroke), hospitalization for HF, and composite kidney outcomes with emphasis on significant decline in eGFR, progression to end-stage kidney disease, or death from kidney disease. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, we derived pooled estimates for each PICO question and appraised evidence certainty on an outcome-by-outcome basis. With GRADE, evidence certainty is appraised across 5 domains: risk of bias, indirectness, imprecision, inconsistency, and publication bias. This extensive and detailed analysis is provided in the companion article.7 We used a modified Delphi process in which panelists voted on and suggested refinements to draft statements to derive the final statements. All conflicts of interest were declared. For recommendations to go forward a two-thirds voting majority was required. It should be emphasized that the voting was primarily an evaluation of the commissioned meta-analysis which, by design, included all available data and not just trial-specific data. Practical points were identified through surveying the panel members, and through examining other published guidelines.[3-6] The primary writing group also submitted a draft for peer-review by a secondary panel, after which peer-review was undertaken by the CCS Guideline Committee. Simultaneously but separately, the de novo systematic review and meta-analysis supporting this guideline was peer-reviewed.[7] The overall goal of the process was to produce guidelines on the basis of the best, most comprehensive, and most up to date evidence that would allow clinicians and patients to make collaborative treatment decisions. These guidelines were undertaken under the auspices of the Guideline Committee of the CCS without representation or funding from the pharmaceutical or device industry.

Evidence Synthesis and Recommendations at a Glance

As indicated previously, the recommendations are on the basis of a companion, systematic review and meta-analysis to which the reader is referred for details of data synthesis and GRADE tables summarizing evidence quality.[7] Table 1 herein is a summary of the relative benefits (hazard ratios [HRs]) and event reductions per 1000 treated patients. The resulting recommendations are provided in Table 2. A summary of the specific trials, the medications used, and the cardiorenal outcomes that were significantly improved are provided in Table 3. A general approach to the integration of GLP-1RA and SGLT2i as cardiorenal agents into cardiovascular practice is provided in Figure 1.


The opportunity to help reduce cardiorenal morbidity and mortality through the use of diabetes-related drugs requires vigilance in identification of appropriate patients for therapy. Assessment of HF symptoms is commonplace and fosters appropriate use of imaging and biomarker tests to identify HF and its phenotype. Serum creatinine and eGFR are often measured to ensure appropriate CV drug dosing or in anticipation of diagnostic tests using contrast media. But measures of A1c and urine albumin-creatinine ratio (UACR) are often not included to identify patients who might well benefit from use of cardiorenal risk-reduction drugs. Consequently, we have included a general recommendation to undertake these tests as part of a comprehensive CV risk assessment. Moreover, digital health technologies might further facilitate identification of appropriate patients.[27] The reader is referred to the major society guidelines for more detailed recommendations regarding screening and symptom evaluation processes.[3-6]


Cardiovascular specialists are encouraged to assess kidney and glycemic status through measurement of eGFR, UACR, and A1c and to document left ventricular ejection fraction (LVEF) when evaluating symptoms of HF.


1. Mancini GBJ, Cheng AY, Connelly K, et al. Diabetes for cardiologists: practical issues in diagnosis and management. Can J Cardiol 2017;33: 366-77.

2. Mancini GBJ, Cheng AY, Connelly K, et al. CardioDiabetes: core competencies for cardiovascular clinicians in a rapidly evolving era of type 2 diabetes management. Can J Cardiol 2018;34:1350-61.

3. Lipscombe L, Butalia S, Dasgupta K, et al. Pharmacologic glycemic management of type 2 diabetes in adults: 2020 update. Can J Diabetes 2020;44:575-91.

4. Senior PA, Houlden RL, Kim J, et al. Pharmacologic glycemic management of type 2 diabetes in adults: 2020 update – the user’s guide. Can J Diabetes 2020;44:592-6.

5. O’Meara E, McDonald M, Chan M, et al. CCS/CHFS heart failure guidelines: clinical trial update on functional mitral regurgitation, SGLT2 inhibitors, ARNI in HFpEF, and tafamidis in amyloidosis. Can J Cardiol 2020;36:159-69.

6. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int 2020;98:S1-115.

7. Ali MU, Mancini GBJ, Fitzpatrick-Lewis D, et al. The effectiveness of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists on cardiorenal outcomes: systematic review and meta-analysis. Can J Cardiol 2022;38:1201-10.

27. Whitelaw S, Pellegrini DM, Mamas MA, Cowie M, Van Spall HGC. Barriers and facilitators of the uptake of digital health technology in cardiovascular care: a systematic scoping review. Eur Heart J Digit Health 2021;2:62-74.

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