People tend to focus on the negatives when it comes to medications. Rightly so, as medications can sometimes have nasty side effects or complications. Weight-loss medications are no different, and I have already discussed many potential risks and side effects, like fatigue, nausea, heartburn and constipation, just to name a few.
So today, I want to do something different. I want to talk about other potential benefits of Saxenda outside of weight loss. In particular, can Saxenda benefit your heart?
So let’s get into it!
LEADER Trial – Diabetes and Obesity
Now some of you might be thinking, ‘well, if Saxenda can help with weight loss, then obviously it can benefit your heart. Because ‘being fat is bad for your health!’
While this is partially true in some instances, there might be more to the story.
To help with our discussion, we’ll review the LEADER Trial by Marso and friends.
Saxenda is ONLY indicated for obesity management up to a max dose of 3mg daily.
In contrast, Victoza is ONLY indicated for diabetes management up to a max dose of 1.8mg daily.
I know; don’t worry if you continue to be confused because same – I am also confused.
Anywho, the LEADER Trial was a randomized, double-blind, placebo-controlled trial that was trying to answer the question:
“In patients with Type 2 Diabetes, does Liraglutide (Victoza/Saxenda) affect cardiovascular mortality, nonfatal myocardial infarctions or nonfatal strokes when compared to placebo?”
“In patients with diabetes, does Liraglutide (Victoza/Saxenda) increase, decrease, or have a neutral effect on the risk of heart attacks, strokes, or death due to heart disease when compared to a placebo?”
Marso and friends found a total of 9,340 individuals with Type 2 diabetes and an A1C >7%. These individuals also had to be at high risk of and/or already have heart disease.
To give you the specifics, participants were >50 years old and had one existing heart disease, such as a previous heart or stroke, kidney disease, or heart failure.
Or, participants were >60 years old and had one or more risk factors that may lead to heart diseases such as high blood pressure, protein in their urine (indicates kidney function is decreasing), or dysfunction in their heart pumping ability.
Age is an important factor in our risk of heart disease. Unfortunately, as we age, our risk of disease increases – even if we are doing everything perfectly. Like driving that new car off the lot, it immediately depreciates in value and continues until it finally breaks down for good and must go to car heaven.
If you want to know your risk of developing heart disease, you can check out this fancy calculator: https://cvdcalculator.com/. You will need a few things, and to fully understand it, I would recommend you review it with your healthcare provider!
Now I wanted to mention the above because it is important for a couple of reasons.
First off, they use individuals that are at a higher risk of the said disease they are looking at because there is a better chance of seeing some benefit (or not) from their intervention, which in this case is liraglutide!
Further, this also allows the study to be shorter in duration and require fewer participants. These studies are already hella expensive, and a trial like this needs to go on for generally five years to give us the full picture.
Have you tried following nearly 10,000 people for almost five years? Growing up, I watched my parents’ friends barely be able to follow their kids around to prevent them from killing themselves. Can you imagine doing that with 10,000 adults?
Victoza vs. Placebo
Now Marso and friends took these 9,340 participants and split them into two groups. One group received Victoza (Liraglutide) 1.8mg once daily, and the other group received a placebo to inject once daily.
Both groups continued with usual care – i.e. following up with their physician and having medications added or making lifestyle changes as needed to manage their blood sugar levels with the goal of getting participants A1C < 7%. They then followed these individuals for a minimum of 42 to a maximum of 60 months, or three and a half to five years, for those of us that don’t have babies or toddlers and use appropriate measures of time.
Marso and their pals were looking primarily at the number of heart attacks, strokes, or death from heart disease that occurred over the follow-up period – in the healthcare research world, we add the number of those events that occur together and call it the MACE (Major Adverse Cardiac Events) outcome.
The author’s main goal and the drug company’s main hope was that Liraglutide did not lead to more MACE events compared to the placebo. A neutral result was a good result, and if it was shown to be more effective, well, that would be the cherry on top.
So what did Marso and their friends find?
There were 4,668 individuals in the Liraglutide group, and it was found that 608 individuals or 13% experienced a MACE event. This was compared to the placebo group, where 4,672 individuals and 694 or 14.9% of those individuals experienced a MACE event.
It is clear that the addition of Liraglutide was not only neutral compared to the placebo, but it also led to a smidge better outcomes compared to the placebo.
To provide more perspective, we would need to take 66 individuals, similar to those in this trial, and provide them with Liraglutide for a minimum of three years for one of them to receive the benefit of not having a MACE event. (I know, it doesn’t sound nearly as good when we spell it out like that.) For people that don’t have diabetes or are at a much lower risk of heart disease, we would likely need to treat a lot more people for a longer period of time for one individual to get a benefit.
Findings from the Results
So what can we conclude from those results? Well, at the very least, Victoza/Saxenda will not increase your risk of heart disease, and they may provide some small benefit in reducing that risk!
Unfortunately, we do not have any specific trials looking at using Liraglutide up to a dose of 3mg daily and individuals who don’t have diabetes – so I can’t throw any specific numbers at you. What I can tell you is that there are trials being done with drugs like Wegovy in individuals that have Obesity and no diabetes to determine what kind of benefit may or may not be provided! I will, of course, update you when that trial is published!
If you have a curious mind like myself – you may be wondering, ‘Ok, that’s cool, but there wasn’t much weight loss or difference in blood sugars, so HOW do these drugs potentially benefit the heart?’
Tell us the heart benefits, Dr. Dan…
So yes, there is a potential benefit from managing blood sugars and helping with weight loss, but GLP-1s such as Saxenda may also modulate other things such as reducing blood pressure; high blood pressure is the silent killer.
They may also decrease cholesterol, particularly LDL, the bad cholesterol which is the primary driver of heart disease. When LDL levels are high, they clog our arteries and, if left unchecked, can eventually lead to the formation of a clot or closing off the vessel so much a person can have a heart attack or stroke.
Finally, they may also affect our platelets! Platelets are the guys that form clots – have you ever cut yourself and a scab formed? That is the work of your platelets! Sometimes platelets will form scabs or clots inside of our vessels if vessels are too clogged with LDL and end up bursting. Your platelets will get to work forming a clot to manage the burst but may also block the blood vessel. You can probably guess what happens next!
GLP-1 medications seem to help regulate and modulate all these functions and thus may provide the benefit of reducing your risk of heart disease!
Pretty darn cool, right?!
Ok, maybe it’s just me. Anyways that is it for today.
PMID: 27295427 https://pubmed.ncbi.nlm.nih.gov/27295427/
PMID: 32765722 https://pubmed.ncbi.nlm.nih.gov/32765722/
I hope you enjoyed learning a little bit more about these weight-loss medications! Of course, if you have any questions, please do not hesitate to reach out.
Until next time my friends.
Stay tuned for future articles, and of course, always remember – small tweaks lead to massive peaks.
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