Diabetes Medications That Reduce Cardiovascular Risk
Diabetes Medications That Reduce Cardiovascular Risk – A new study from St. Michael’s Hospital in collaboration with Western University shed light on how a class of drugs that help control blood sugar for patients with type 2 diabetes can also protect against heart disease.
The results of the EMPA-HEART CardioLink-6 study, presented today at the ESC 2019 Congress, organized by the European Society of Cardiology, and jointly published in
Diabetes Medications That Reduce Cardiovascular Risk
, focus on the effect of a diabetes drug — empagliflozin — on the repair of blood vessel cells and the resulting risk of heart disease. Empagliflozin is a drug that falls into the category of drugs called SGLT2 inhibitors, which lower blood sugar.
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Research suggests that circulating progenitor cells — which are found in the bone marrow and play a role in heart health — along with inflammatory cells are controlled by this diabetes drug. For patients with diabetes and at risk of heart disease, such drugs can provide heart protection by relieving damaged cells that may perpetuate heart disease by causing defective repair. in the veins.
“We have seen large clinical trials that give us strong evidence that SGLT2 inhibitors can also protect our diabetic patients from heart disease,” said Dr. Subodh Verma, cardiac surgeon and scientist at the Keenan Research Center for Biomedical Science (KRCBS) at St Michael’s Hospital. “Prior to our study, it was not known why this happened.”
According to the World Health Organization, about 1.6 million people died in 2016 due to diabetes. It is the leading cause of blindness, kidney failure, heart attack, stroke, and amputation. Heart disease is a major concern for people with diabetes because they often have impaired repair of blood vessels, making them more susceptible to cardiovascular problems.
The team of St. Michael collaborated with Dr. David Hess, an associate professor at Western University’s School of Medicine & Dentistry and a scientist at the Robarts Research Institute. Dr. Hess is an expert in identifying and quantifying blood vessel progenitor cells. Using blood samples from the EMPA-HEART CardioLink-6 trial, Dr. Hess was able to show that regenerative progenitor cells are reduced in diabetes. In patients who took empagliflozin, however, these progenitor cells recovered.
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“We found that in people with diabetes, not only are the beneficial progenitor cells increased, but we see signs of reduced inflammation and oxidative stress, which can also contribute to cardiovascular disease,” said dr. hess.
For patients with diabetes, this is an important step in reducing the risk of heart disease, said Dr. Worms.
The group of St. Michael includes: Dr. Verma; Rotstein; dr. David Mazer, KRCBS anesthetist and scientist; dr. Mohammed Al-Omran, cardiac surgeon and scientist at KRCBS; dr. Kim Connelly, cardiologist and scientist at KRCBS; dr. Andrew Yan, a cardiologist; and Dr. Lawrence Leiter, an endocrinologist and scientist at the Li Ka Shing Knowledge Institute.
Researchers say these new findings may provide the basis for new therapies for patients with heart disease complicated by diabetes. Do cardiologists prescribe medication for diabetes? The concept seems far-fetched to me. However, somehow over the years, the paradigm for cardiovascular risk reduction has increasingly shifted towards accepting the concept of treating the patient, not the disease.
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We are no longer considered “internists”, “cardiologists” or “endocrinologists”. Instead, we become true “doctors,” crossing interdisciplinary lines and separating the lines between diseases.
I went to the room early to sit in the front. To my surprise, even 25 minutes before the session started, the room was already half full. Apparently, some .19 participants also wanted to learn more about two new drug classes driving this transition: glucose-sodium cotransporter-2 inhibitors (SGLT-2i) and peptide-1 -like receptor agonists. al glucagon (GLP-1 RAs) – and the evolving landscape ahead.
The session was designed to fill the knowledge gap that prevents cardiologists from prescribing diabetes medications, even knowing that cardiovascular outcomes have improved. Cardiovascular disease remains the leading cause of morbidity and mortality in patients with type 2 diabetes (T2D).
The prevalence of diabetes continues to rise. Tight glucose control improves microvascular outcomes, but does not appear to have the same demonstrated benefit on cardiovascular outcomes. Metformin and lifestyle changes are recommended as first-line interventions in T2D.
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Until recently, we hit a roadblock to reduce diabetes risk. But now, SGLT-2i and GLP-1 RAs have been shown to reduce cardiovascular events through mechanisms independent of their glucose-lowering effects. This led to a paradigm shift: from the traditional strategy of targeting glucose control to a more comprehensive strategy of reducing cardiovascular risk in T2D.
…the paradigm for cardiovascular risk reduction has increasingly shifted toward embracing the concept of treating the patient, not the disease. We are no longer considered “internists”, “cardiologists” or “endocrinologists”. Instead, we become true “doctors,” crossing interdisciplinary lines and separating the lines between diseases.
What I found particularly “encouraging” was the jury’s discussion of finding the “sweet spot” between cardiovascular care and diabetes, with an emphasis on the role of cardiovascular disease specialists. to co-manage patients with T2D.
As I listened to the speakers, I couldn’t help but think about the rapid rise to stardom of SGLT-2i and GLP-1 RA. Originally designed as add-on classes of diabetes drugs intended to lower blood sugar in adults with T2D, they have nevertheless entered the ever-competitive landscape of drugs that improve cardiovascular consequences.
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The first SGLT-2i is a natural compound extracted from apple skin called phlorizin. However, it is poorly tolerated with significant gastrointestinal side effects and poor oral bioavailability. Technology has improved over time and the tolerability and pharmacology of the drug have favored its use.
The mechanism of action of this class of drugs is the inhibition of sodium-glucose cotransporter-2 in the nephron, which is responsible for 90% of urinary glucose reabsorption; Inhibition causes glycosuria and reduced serum glucose levels. The level of glycosuria depends on the level of glucose in the blood. The risk of hypoglycemia is low.
Cardiovascular benefits are thought to result from diuretic, natriuretic, hypotensive, and weight loss effects. It may also have favorable effects on the sympathetic nervous system, myocardial metabolism, and cardiac remodeling.
SGLT-2i class drugs include canagliflozin, dapagliflozin, and empagliflozin, each given orally. They can be used as monotherapy agents or in combination with other diabetes drugs, such as metformin, after showing benefit in several cardiovascular outcome studies comparing the drug to placebo (Table 1).
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SGLT-2i has shown efficacy, with significant reductions in hospitalizations for heart failure and progression of kidney disease. Modest effects were also shown in major adverse cardiovascular events (MACE), including non-fatal myocardial infarction (MI), cardiovascular disease, and stroke. Empagliflozin has been shown to significantly reduce cardiovascular and all-cause mortality.
All this benefit with SGLT-2i comes at the cost of an increase in genital yeast infection. And in patients with severe peripheral arterial disease, a possible increase in the risk of amputations, as seen with canagliflozin. The increased risk of amputations does not appear to be a class effect, as it has not been observed with other SGLT-2i, and the US Food and Drug Administration (FDA) black box advisory specifically mentions only canagliflozin.
In patients treated with diuretics, SGLT-2i may also increase the risk of hypovolemia/hypotension. According to FDA labeling, SGLT-2i should be discontinued in acute renal failure or renal insufficiency, and the doses of diuretics may also need to be adjusted when starting SGLT2i therapy.
As the speakers talked about the adverse effects of these drugs, including genital yeast infections, I chuckled to myself knowing that more of us cardiologists must feel that comfortable in the treatment of candidal vaginitis in women and balanitis in men and we can no longer continue to “stay on top. the diaphragm”.
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The other major paradigm-shifting class of glucose-lowering drugs for reducing cardiovascular risk in T2D is the GLP-1 RA. In some individuals with T2D, the physiological response to an oral glucose load, as mediated by the incretin system, is impaired.
This results in a small effect of GLP-1, with a reduced ability to secrete insulin, thereby increasing insulin resistance with further reduction and resistance to the expression of the GLP-1 receptor and its downstream action. GLP-1 agonists stimulate GLP-1 receptors, which inhibit these effects, resulting in increased insulin secretion and sensitivity, increased satiety, decreased body weight, and lower HbA1c. .
The first GLP-1 RA (exenatide) was approved in the United States over a decade ago. Since then, several agents have been approved, with different durations of action:
Of the six FDA-approved GLP-1 RAs, only liraglutide and semaglutide have been shown to reduce cardiovascular events. In cardiovascular outcome studies, GLP-1 RA compared to placebo led to consistent and significant reductions in three-point MACE (Table 2).
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…how do we get providers to accept these therapies, and should they be “owned” by cardiologists, primary care, endocrinologists, or accepted by all, regardless of their specialty?
GLP-1 RAs have the benefit of aiding weight loss. Analyzes of existing studies also suggest that this type of drug may provide renal benefits, possibly by increasing urine output and natriuresis. In the LEADER process, there
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