Two classes of glucose-lowering drugs reduce risk of heart failure, kidney complications and death – even in patients without type 2 diabetes

New Cardiorenal Protection Guideline urges use of GLP-1RA and SGLT2i drugs to save lives; as many as three million Canadians could benefit.

Two classes of drugs commonly prescribed to lower glucose levels in people with type 2 diabetes have been shown to reduce hospitalization and death in patients with heart failure and chronic kidney disease, whether they have diabetes or not, according to a new Guideline published in the Canadian Journal of Cardiology.

The potential benefit of wider access to these new drugs and better implementation could be felt by as many as three million Canadians living with heart failure, chronic kidney disease, and/or type 2 diabetes, says Vancouver cardiologist Dr. John Mancini.

Dr. Mancini co-chaired an expert panel that developed the first-ever formal Canadian Cardiovascular Society (CCS) Guideline for the two drug classes: 2022 CCS Guideline for Use of GLP-1 Receptor Agonists and SGLT2 Inhibitors for Cardiorenal Risk Reduction in Adults.

“We anticipate longer lives, fewer cardiovascular deaths, fewer hospitalizations for heart failure, and fewer kidney complications going forward,” Dr. Mancini says.

The CCS Guideline was developed after a rigorous review of research studies and trials around the world. While targeted at cardiovascular specialists and community cardiologists, it is also aimed at nephrologists, pharmacists, internists, and policymakers.

“These drugs need to be integrated early into patient management plans to reap the best long-term benefits,” says Dr. Mancini, Professor of Medicine at the University of British Columbia. “We can prolong lives; we can prevent major adverse cardiovascular events; and we can protect the kidney.”

Toronto endocrinologist Dr. Alice Cheng, who served on the expert panel, agrees it’s important to get this message out.

“SGLT2i and GLP-1RA may have started as diabetes drugs but they have turned out to do so much more,” Dr. Cheng says. “It is imperative that everyone involved in the care of people living with heart, kidney and/or type 2 diabetes be comfortable with their use as these therapies no longer “belong” to any specialty – but rather belong to the patient.  We need to share our experience with our colleagues to ensure safe and effective use.”

According to the Guideline:

Compared to standard of care, treatment with SGLT2i showed:

• 14% reduction in cardiovascular mortality;
• 13% reduction in any-cause mortality;
• 12% reduction in major cardiovascular events;
• 31% reduction in heart failure hospitalization;
• 24% reduction in cardiovascular death;
• 10% reduction in non-fatal myocardial infarction; and,
• 36% reduction in kidney composite outcome.

Treatment with a GLP-1RA was associated with:

• 13% reduction in cardiovascular mortality;
• 12% reduction in any-cause mortality;
• 14% reduction in major cardiovascular events; and,
• 16% reduction in non-fatal stroke.

Additionally, ongoing studies may clarify what appears to be a potentially positive role of GLP-1RA for patients with heart failure or kidney disease.

The Guideline was developed with key content experts from Diabetes Canada, the Canadian Heart Failure Society, and the Canadian Society of Nephrology.

Top Takeaways

1. GLP-1RA and SGLT2i protect the heart, kidneys and vasculature and reduce death and hospitalization. They are not just for lowering A1C. “The range of reductions is profound,” Dr. Mancini says. Use of these drugs is a paradigm shift for cardiovascular specialists.
2. Cardiovascular specialists need to screen patients to identify the opportunities to use these drugs. They should routinely look at the patient’s A1C, renal function including estimated glomerular filtration rate (GFR), urine albumin creatinine ratio, and to be alert to symptoms of heart failure.
3. The Guideline contains practical tips for safe implementation and integration in patient care for both classes of drugs.
4. The Cardiorenal Guideline overlaps with those of other medical societies. Refer to those other societies, listed in the Guideline, for the more detailed elements of their clinical practice recommendations.
5. As the voice of cardiovascular medicine in Canada, the CCS advocates for lowering access hurdles to medications not covered by drug plans.