VESL Wall, Issue #2, April 2021
Issue #2, April 2021

This month on the VESL Wall, we explore the cardiovascular and renal protective effects of SGLT2i in patients with and without diabetes, and also consider the unique challenges of cardiovascular health in the developing world. See all issues of the VESL Wall at

View a 10-minute video summary of the April issue of the VESL Wall with Dr. Robert Hegele >> Video Summary VESL Wall Issue #2 [10 min]
Call to action: SGLT2i and GLP-1RA to reduce cardiovascular events in T2D

In a beautifully written Circulation editorial, Dr Alice Cheng provides context and interpretation of an observational study of CV outcomes performed in T2D patients taking glucagon-like peptide receptor agonists (GLP-1RA) when a sodium-glucose cotransporter-2 inhibitor (SGLT2i) is added. In the study, data were extracted from three large insurance databases in the US and included 12,584 patients in each group. The addition of SGLT2i to GLP-1RA therapy was associated with a 24% improvement in composite cardiovascular outcomes and a 36% reduction in hospitalization for heart failure. Treatment rates with SGLT2i and GLP-1RA therapies are currently suboptimal. The editorial states that if evidence-based guidelines were implemented in 70% of the world’s population with T2D, there would be 800,000 fewer premature deaths per year. Dr Cheng makes an impassioned call to action for all specialties collaborating in the care of T2D patients to follow the evidence that cardiovascular outcomes can be improved with SGLT2i and GLP-1RA therapy, used earlier and either alone or in combination in patients at risk.

Read more: [Sosido Link] Cheng AYY. Why Choose Between SGLT2 Inhibitors and GLP1-RA When You Can Use Both?: The Time to Act Is Now. Circulation. 2021;143(8):780-782.

Evidence for cardiovascular and renal protection with SGLT2i in CKD and HF

Building on the theme of benefits SGLT2i in T2D (and also in patients without diabetes), Cherney and Verma review the evidence for dapagliflozin, canagliflozin, and empagliflozin in patients with nondiabetic kidney disease. A growing body of data suggests the cardiovascular- and renal-protective effects of these medications are independent of glycemic control in people with diabetes. The DAPA-CKD trial enrolled over 4,000 patients with CKD and eGFR between 25-75 ml/min/1.73m2 . About one-third of patients did not have a diagnosis of diabetes in this trial. Treatment with dapagliflozin resulted in a 39% decline in the composite primary endpoint of ≥50% eGFR decline, end-stage kidney disease, renal death, or cardiovascular death. Results are consistent with the DAPA-HF (dapagliflozin in chronic HF) and EMPEROR-reduced (empagliflozin in HFrEF) trials. The authors provide a scholarly and engaging review of multiple mechanisms that explain the cardiorenal benefits of SGLT2i treatment. They also note several populations for whom SGLT2i should not be used, or used with caution, including those with diabetic ketoacidosis, mycotic genital tract infections, and other patients aligned with the known safety profile of these agents.

Read more: [Sosido Link] Cherney DZI, Verma S. DAPA-CKD: The Beginning of a New Era in Renal Protection. JACC Basic Transl Sci. 2021;6(1):74-77. Published 2021 Jan 25.

A perspective on cardiovascular disease prevention and treatment in developing countries

In their recent review with potential global implications, Teo and Rafiq note that lower-income countries have recently caught up to the developed world in their rates of cardiovascular disease, and that 80% of the global disease burden is found in these poorer countries. They summarize findings and limitations from the INTERHEART and INTERSTROKE case-control studies. They also cite data from the PURE study, which demonstrated that although high-income countries have the highest risk-factor burden for cardiovascular disease, they also have the lowest rates of major CVD and death when compared to middle- and low-income countries. One factor is the differential impact of urbanization in developed versus developing countries. Guidelines published for higher-income countries must be adapted before being applied to the developing world; consideration must be given to differences in drug access, affordability, as well as the unique environmental and cultural challenges found in these countries.

Read more: [Sosido Link] Teo KK, Rafiq T. Cardiovascular risk factors and prevention: a perspective from developing countries [published online ahead of print, 2021 Feb 18]. Can J Cardiol. 2021;S0828-282X(21)00111-2. doi:10.1016/j.cjca.2021.02.009

  1. Clinical trial evidence is nudging SGLT2 inhibitors and GLP-1 receptor agonists, individually and in combination, towards the front line of pharmaceutical agents for prevention of cardiorenal complications in diabetes.
  2. SGLT2 inhibitors are assuming notable prominence from a reno-protective perspective.
  3. Cardiovascular risk profiles are distinctive and significant in developing countries, a factor to consider in the assessment of recent immigrants to Canada.

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