GLP-1 Receptor Agonists- what are they?

I have practiced functional medicine for 9 years now. Every patient walking through my office doors from the time I started this practice to now has always come to me with one goal-” I want to get off my medications”, that is until now.

Today not a single week goes by without someone asking me about the “new weight loss” medication. This is not a new medication but its impact on weight which was considered a side effect has proven to be the effect we want. These are the group of medications called glucagon-like peptides. This is a little protein produced by your gut that increases insulin and helps control glucose.

Type 2 diabetes is on the rise and is a disease of abundance – abundance of food and stress. In an effort to control blood sugar, every aspect of the blood sugar journey was looked at.

GLP-1 was a group of proteins secreted by the gut that increased insulin but did not last in the system long enough as it was destroyed quickly by another hormone also produced by the intestines. These hormones were discovered in the 1980s but came into clinical medicine in 2005.

They were brought into the market to control diabetes and of course, but it was noticed that it not only controlled sugars but patients began to lose weight. Nova Nordisk the company that put out Ozempic slowly started being used for weight loss in prediabetics. However, it was initially approved only for diabetes. Then Lilly Pharmaceuticals brought on Mounjara and Novo Nordisk brought on Wegovy all approved for weight loss.

So how do these medications work and should you be on them if you have struggled with weight loss?

GLP1 -receptor agonists ( that is these synthetic versions of your natural hormone act upon the cells that receive this medication like it is a hormone naturally produced), work both at the level of your gut and your brain. In the gut, it slows the emptying of the stomach so you are full longer. They last longer than the natural hormones so work longer on the sugar and weight.

In the brain its exact mechanism is unknown. It works on three different parts of the brain the net result is it gives you a lower appetite, some nausea, and fullness almost a feeling like you are ill. This illness-like feeling you will adjust to and then the weight loss begins.

The studies have been done now for 120 weeks. So a little over 2 years for weight loss.

Most people lose weight rapidly. It is not just the weight loss but they have better blood sugar control, better blood pressure, and better cholesterol. So all in all a perfect drug right?

The jury is not out but here is what you need to know.

What you need to know:

The weight loss you experience is rapid and reaches a nadir at 60 to 68 weeks that is within a little over a year you will reach your lowest weight which is 17%  of your body weight so if you are 100 kilograms that is 220 lbs you will lose 17 kilograms or 37 lbs. Which is astounding.

This means you will still be overweight unless you are well over 6 feet tall.

So once you reach this goal here is what you need to know. If you stop the medication, the rate at which you lost the weight the whole weight comes back as fast as it left you.

So in another 60 weeks, most people gain back all of the weight but if you lost over 20% of your baseline weight you may have a net 5.7 % weight loss. So going back to our example of 100 lbs or 220 lbs you will have a net weight loss off the medication of 5.7 kilograms or 12.5 lbs.

Why would one stop this?

It is a weekly injection, so not really convenient-  there is one oral medication called Rybelsus. It is not cheap if you do not have insurance approval.

The pharmaceuticals have a savings program that lasts for 12 months but after that, it can cost you from 580 $ to 1100$ a month. The same amount if you paid a trainer to help you at the gym 3 to 4 times a week.

Are there any side effects?

Yes usual nausea, vomiting, and diarrhea all of which get better, but there is loss of muscle mass and some studies show some increase in fat mass. Further, it can cause inflammation of the pancreas.

There is ongoing research to see if they can make drugs that will not cause these side effects and I am sure they will hit the market in the next few years.

Who is it not good for?
  • Diabetics lose less weight than non-diabetics. It is good for their sugar control and reduction of cardiovascular disease.
  • If you had pancreatic problems or thyroid nodules there is a caution to the use of this group of medications.
  • You have to take it for the rest of your life. So if you are not a compliant person this may be a difficult one.

What if you exercised and ate well would you gain the weight back?

Most of the folks in these studies were put on a caloric deficit of 500 calories a day and exercised 150 mins a week. It was successful as they did not have hunger as the medication induced the anorexia naturally.

So if you are willing to go on a medication for the rest of your life this is a great choice and I am sure the research will make it better with time. You will always need the doctor or always need insurance coverage or pay out of pocket.

Weight Watchers are bringing it to their programs. So are many med spas. So this medication is being used widely. Access to this medication is easy, but there is a lot more thought that needs to go into staying on this medication for the rest of your life. If that is something you can do go on as it may as well work for you. Why some people have more side effects than others is unknown but starting at a very low dose seems to help.

Always speak with your doctor before you get on any medications as you need regular check-ups till we know enough.

Hippocrates said medicine should do 2 things – it should help and do no harm. If the GLP-1 receptor agonists fit that description is yet to be seen.

 dR. Chellam

PS: My most sustainable weight loss is developing the habit of eating mindfully, exercising, and adding some supplements that can help digest food and process it.

To get my take on supplements that help click on this Link

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