Abstract
Background: Cardiorenal-metabolic disease reflects the interdependence of obesity, type 2 diabetes, chronic kidney disease (CKD), heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD). Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shifted management from glucose lowering alone toward organ protection. Canada provides a useful practice framework because national and specialty guidance now prioritizes these therapies according to cardiovascular, kidney, heart-failure, and weight-related risk.
Objective: To summarize the complementary mechanisms, outcome evidence, and practical use of SGLT2 inhibitors and GLP-1 RAs in Canadian cardiorenal-metabolic care. Summary: Diabetes Canada recommends prioritizing agents with demonstrated cardiorenal benefit in people with type 2 diabetes and high cardiovascular risk, HF, or CKD, even when A1C is already at target. The Canadian Cardiovascular Society recommends SGLT2 inhibitors across HF and albuminuric CKD and supports either an SGLT2 inhibitor or GLP-1 RA in type 2 diabetes with established ASCVD or multiple risk factors. Obesity Canada further recommends semaglutide 2.4 mg for selected patients with obesity and established ASCVD and recognizes its benefits in obesity-related HFpEF. Mechanistically, SGLT2 inhibitors predominantly reduce intraglomerular pressure, volume stress, and HF events, whereas GLP-1 RAs provide greater weight loss, glycemic lowering, and atherosclerotic risk reduction. Combination therapy is biologically attractive and endorsed as reasonable in selected Canadian patients, but additive hard-outcome benefit has not been definitively established in randomized combination trials.
Conclusion: Canadian practice increasingly supports phenotype-driven selection of these classes, with combination therapy considered when cardiovascular, kidney, HF, glycemic, and weight-related priorities overlap.
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Ethics & Declarations
Author Contributions
All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by all authors. All authors read and approved the final manuscript.
Ethics Approval and Consent to Participate
Not applicable. This study did not involve human participants, animal experimentation, or confidential patient clinical data.
Consent for Publication
Not applicable, or informed consent for publication was obtained from all individual participants where relevant.
Competing Interests
The authors declare that they have no competing financial or non-financial interests.
Funding
The authors declare that no funds, grants, or other financial support were received during the preparation of this manuscript.
Data Availability Statement
Data sharing is not applicable to this article as no new datasets were generated or analyzed during the current study.
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© 2026 MOHAMED ABDELLATIF et al. International Journal of Clinical Pharmacy and Medicine.