Monday, October 4, 2021

Diabetes Drug Shows Promise as Heart Failure Treatment

UMC issued the following article authored by Karen Bascom. 

 For years, clinical trials have tried and failed to discover an effective treatment for a common kind of heart failure.

That is, until a global study co-led by a University of Mississippi Medical Center physician found convincing evidence for a new approach to treat heart failure with preserved ejection fraction, or HFpEF.

The paper, published in the New England Journal of Medicine August 27, showed that the diabetes drug empagliflozin reduced the risk of cardiovascular death or heart failure hospitalization by 21 percent.

For a condition that affects millions of Americans with no known therapy, that’s a substantial result, said Dr. Javed Butler, chair of the Department of Medicine at UMMC and co-author of the study.

“Until this trial, we had no effective therapies for patients with this form of heart failure. This is the only major cardiac disease where this was the case,” said Butler, Patrick H. Lehan Chair of Cardiovascular Medicine.

Heart failure happens when the heart cannot supply adequate blood to the body for its needs at normal heart pressures. It has many causes, including high blood pressure and coronary artery disease. It causes shortness of breath, tiredness, irregular heartbeats and swelling from fluid. If the heart does not function normally, it cannot provide adequate oxygen to the body.

There are two main types of heart failure. In heart failure with reduced ejection fraction, or HFrEF, the heart muscle does not contract as well as it should. In HFpEF, the heart contraction may be normal but for a combination of reasons, it cannot pump effectively.

Butler says the “complex pathophysiology” of HFpEF is a major reason why the condition has been treatment-resistant so far.

“In heart failure with reduced ejection fraction, the pathology is mostly about the heart itself and the available drugs target that issue,” Butler said. In preserved ejection fraction, multiple conditions can contribute to the dysfunction, including the heart, kidney disease, obesity, and metabolic disorders.

The U.S. Food and Drug Administration approved empagliflozin, sold under the brand name Jardiance, in 2014 to help type 2 diabetes patients manage their glucose levels. A sodium-glucose cotransporter 2 (SGLT2) inhibitor, it limits the kidneys’ ability to reabsorb sugar back into the bloodstream. Instead, the body passes extra sugar in the urine.

Butler recalls a “very vivid memory” from a few years ago that helped lead to the trial.

“I was talking with a few of my colleagues around the globe as we were starting to look at the pharmacodynamic profile of this new diabetes drug,” Butler said. That brought up the question: “If a drug has this kind of action on the body, can it have beneficial cardiovascular effects regardless of diabetes? Is it actually a cardiovascular drug that also lowers glucose?”

He and his colleagues arranged a series of clinical trials to learn whether empagliflozin could help solve one of the most pressing treatment challenges facing cardiologists. But not everyone in the medical community thought it was worth a shot.

“We received pushback when proposing to test if a diabetes drug could treat heart failure even in those without diabetes,” Butler said.

In the recent NEJM study, Butler and his colleagues recruited 5,988 HFpEF patients in 23 countries for a double-blind trial. The participants received either daily empagliflozin or a placebo in addition to their regular treatment. The research team followed each participant for a median time of 26 months to monitor for heart failure-related hospitalization or death.

The study found that empagliflozin reduced the risk of hospitalization or death from heart failure by 21 percent compared to placebo, driven by a 29 percent decline in hospitalization. The treatment group had a nine percent lower risk of death during the study period, although the result was not statistically significant on its own.

Most interestingly, Butler and his colleagues saw the same effect in both patients who did and did not have diabetes.

Dr. Mark Drazner of the University of Texas Southwestern Medical Center wrote in NEJM that trial had “a result that represents a major win against a medical condition that had previously proved formidable.”

The “trial should contribute to a change in clinical practice, given the paucity of therapeutic options available for patients with heart failure and a preserved ejection fraction,” Drazner wrote.

Butler and colleagues published other results from this trial August 29 in Circulation. They showed that the empagliflozin-treated patients had less severe heart failure symptoms at 12 weeks and two years after the start of treatment.

The team also found that empagliflozin has similar effects in HFrEF, which they published October 8, 2020 in NEJM. This finding set in motion the FDA’s decision to approve the drug for HFrEF on August 18.

The FDA has not yet approved empagliflozin to treat HFpEF. However, Butler said the manufacturer will submit data for review.

With these findings, Butler feels very comfortable about calling empagliflozin not simply a diabetes drug, but a “cardiovascular-risk modifying agent.”

“When a drug works on common underlying cardiovascular mechanisms, it has the potential to treat many different cardiovascular conditions,” Butler said.

He gave two examples. Angiotensin-converting enzyme, or ACE, inhibitors received initial FDA approval to treat hypertension, but doctors now use them to treat heart attacks, stroke and HFrEF. Statins lower blood cholesterol and in turn decrease the risk of heart disease and stroke.

Will empagliflozin join their ranks? Butler is a lead investigator on clinical trial examining whether the drug can lower the risk of cardiovascular events after a heart attack. He says another study is testing its ability to slow the progression of kidney disease.

However, he said there are cases where this drug will not be helpful. Empagliflozin should not be used for patients with type 1 diabetes, those on kidney dialysis or those with an allergy to the drug.

“As clinicians, we cannot take the average result from this trial and simply apply it to the patient sitting in front of us,” Butler said.

Butler describes the advancement of medicine as a “two-front war.” On one end, there is evidence generation, the basic science and clinical trials that lead to new knowledge. At the other is implementation: making that knowledge work for the benefit of patients.

“None of this science, none of the sacrifices of the 6000 patients in this trial – none of that matters unless we actually implement the findings in clinical practice.” 


 

20 comments:

Anonymous said...

Good things are happening at Ole Miss.

Anonymous said...

Or, cut out sugar, ultra processed foods, inflammatory "vegetable" oils and eat real foods and then have no need for Type 2 diabetes/heart failure pharmaceuticals in the first place.

Anonymous said...

The irony of "science" using drugs to treat ailments not originally intended after almost 2 years of "science" not allowing available and effective drugs to treat COVID-19. Real classy, science... real classy.

Anonymous said...

@10:31 - please post your science education resume.

Thanks to The Great Society said...

@10:30 AM - as long as the govt. hands out EBT cards to all, with few restrictions on the items purchased, the cycle will continue. EBT cards = votes.

Anonymous said...

10:31 am

You seem to have missed that a research study was conducted and subjected to peer review.

While throwing the " kitchen sink" at Covid was acceptable in early days with judgements about prior use of the drugs, in what universe is it rationally to have doctors to conduct experiments with human patients?

You do, I hope know that is because that has can turned out very badly in the past. Do you need a list of drugs that did harm or are you able to look it up yourself? Do you know the difference between an osteopath and a cardiologist or endocrinologist?

Anonymous said...

Or, cut out sugar, ultra processed foods, inflammatory "vegetable" oils and eat real foods and then have no need for Type 2 diabetes/heart failure pharmaceuticals in the first place.

Sir, this is a Mississippi's.

Anonymous said...

Doesn't take a rocket scientist to research ivermectin. It works. Pfizer is coming out with a 'drug' for covid suspiciously like ivermectin.

NIH -

"Conclusions:

Moderate-certainty evidence finds that large reductions in COVID-19 deaths are possible using ivermectin. Using ivermectin early in the clinical course may reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248252/

Kingfish said...

Suspiciously?

Don't understand science, do you?

Anonymous said...

@11:27a- No need to…

There are PLENTY of studies supporting these treatments, along with real data from other countries who saw EXCELLENT results from many medicines forbidden to our citizens. Make the effort to educate yourself.

Your poor attempt to diss on me doesn’t void the truth.

Anonymous said...

@12:31p- I hope you’re kidding!!

Lol, and who paid for that research and sponsored those peers?? Your opening paragraph tells me everything I need to know about you… you OBVIOUSLY believe and trust everything the government and big pharma presents to you. What a joke!!

You do realize “throwing the kitchen sink” is basically what doctors do all day, every day… right? They are guessing and adjusting, trying to remedy symptoms. Drugs known to be helpful were pulled to push the vaccine process. Doctors were BEGGING to use drugs they were forbidden to use on their patients. The biggest irony in your second paragraph is that your vaccine is LITERALLY being human-tested in REAL TIME!

Wanna talk about drugs that harm?? Pull out ANY Rx insert… they can ALL HARM!!

What does understanding the difference in medical specialties have to do with understanding harmful side effects of drugs? You are absolutely all over the place!

Anonymous said...

"Pfizer is coming out with a 'drug' for covid suspiciously like ivermectin."

Where do you people get this nonsense? Pfizer is working on an anti-viral drug (PF-07321332) but it isn't "like" Ivermectin. The Pfizer candidate is a protease inhibitor (it binds to enzymes and prevents viral duplication) and the "mectin" family work by disrupting electrical activity in particular and targeted cells of invertebrates, i.e. things like parasitic worms. Viruses aren't "alive" and don't have cells of any type, which is among the reasons Ivermectin isn't effective for deactivating SARS-CoV-2 and preventing COVID-19. Certain protease inhibitor combinations ("cocktails") are also being studied for other uses such as anti-protozoals while others are being studied for potential anti-tumor efficacy, but the pharmacology of the PIs and the "mectins" are not similar, much less "suspiciously" so.

Just because an idiot CAN buy both 10W-30 and peanut oil at Walmart doesn't mean they ARE "suspiciously interchangeable," so don't be an idiot and fry fish in motor oil.

Kingfish said...

That's why i didn't take it seriously. I read the article in the Daily Caller and a Christian website. It's clear the authors are very ignorant about science.

Here's a clue: two Ns

Anonymous said...

Like I've said, as long as it's profitable, it will be here one form or another.

Anonymous said...

PS -

The "study" cited above - www.ncbi.nlm.nih.gov/pmc/articles/PMC8248252/ isn't a study, it is merely an analysis of other articles done by a group promoting Ivermectin for COVID-19. It has been discredited because the authors merely cherry-picked some early, small Ivermectin studies with the goal of producing a pro-Ivermectin article.

Folks who do not understand how peer-review, article preprint, etc. work are making fools of themselves by posting links to articles that don't actually support what the person citing it thinks it supports. Those that simply see these links and believe them to be meaningful (or skim over the article and don't understand what they are reading) are making serious errors.

It is really interesting and very disappointing that these same people completely ignore or actively disdain large-scale, well-regarded studies that don't support their loony conspiracy theories (not that they could understand those either) in favor of these "articles" that can be twisted in their completely unqualified minds as proof of something that they just do not in any way prove.

Anonymous said...

"You do realize 'throwing the kitchen sink' is basically what doctors do all day, every day… right? They are guessing and adjusting, trying to remedy symptoms. Drugs known to be helpful were pulled to push the vaccine process. Doctors were BEGGING to use drugs they were forbidden to use on their patients. The biggest irony in your second paragraph is that your vaccine is LITERALLY being human-tested in REAL TIME!"

Utter nonsense. The 99+% of the issues that 99+% of doctors see "all day, every day" are readily and easily diagnosed and treated. There are rare cases in which such is not the case, but even in most of those a little research or consultation with colleagues produces a diagnosis. There are very rare situations in which a "mystery condition" presents itself. There are occasionally new viruses and other pathogens but if there are many cases in short period, ala SARS-CoV-2 and COVID-19, it isn't unknown very long. In such situations, doctors do attempt novel treatments but in the case of viruses, enough is known about them and the pharmacology of anti-virals that many treatments can be easily ruled out as potentials. Where things can and do get interesting is in the attempts to treat the symptoms and tertiary issues as a result of the viral infection.

It is important to realize that just because doctors might try a med off-label to address a particular novel virus or tertiary issue and see some result (good or bad) doesn't mean that med is (or is not) a treatment for the underlying viral infection. Remdesivir in the early stages of COVID is such an example.

Anonymous said...

@6:31p- Your comment is utter nonsense.

You can easily research and find hundreds of thousands of people who have been misdiagnosed and treated with the wrong medication. Reporting agencies claim double-digit MILLIONS are misdiagnosed every year. I’ve witnessed it first-hand with my mother. You’re beyond naive if you think 99+% of conditions are properly diagnosed and treated the first time.

Why are you so offended by the truth that doctors are guessing? Hypothesizing (aka educated guessing) is literally the basis of science.

Just an old white dude said...

Back on topic, folks. All I've got to say is that IF you think you are having a heart attack and IF you find yourself walking into the UMMC ER with such condition, listen up and listen up good: You better go FULL ON FRED SANFORD because the Security guards and the triage staff don't give a flying fuck; you WILL sit for SEVERAL HOURS in a room of perhaps 75 other people most with the sniffles. Filed under been there, done that, twice.

Anonymous said...

"(a)s long as the govt. hands out EBT cards to all, with few restrictions on the items purchased, the cycle will continue. EBT cards = votes.

As an aside, that's exactly the kind of comment that will get you two weeks in the hole over on Facebook. Those teenagers with censorship keys have gone nucking futs! Almost as 'futs' as those of you who look to see what time of day or night people post.

Anonymous said...

Science created diabetes drugs that create dementia. When all someone had to do was quit eating margarine and replace it with cream butter.


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