GLP-1s Part 1: What are the differences between them, and how do you know which one is right for you?

Key Takeaways

• GLP-1s are primarily used to treat obesity and diabetes but can also be effective in the treatment of heart disease, Metabolic dysfunction-Associated Steatotic Liver Disease (previously often called “fatty liver”), and sleep apnea.
• Oral GLP-1s are effective, but only if taken on a strict schedule.
• Temporary digestive side effects are common but can be managed at home with simple adjustments.
• For best results, injection sites should be rotated.
• Obesity is a chronic condition, and as such, it requires lifelong treatment.

Mounjaro^®, Ozempic^®, Wegovy^®, and Zepbound^®, oh my!

By now, you’ve seen ads for GLP-1s, and you or someone you know may be taking one.

But for those of you who are considering a GLP-1 to assist with your weight-loss goals, you may be wondering what the differences between the various medications are and which one is right for you.

Let’s get you on the right track to losing excess weight.

First, what is a GLP-1?

GLP-1 stands for glucagon-like peptide-1, a hormone that is naturally produced in your body after you eat. It works by triggering the release of insulin, slowing digestion, and signaling your brain that you’re full. 

The prescription version of this – GLP-1 receptor agonists – simulates the hormone and is used to treat type 2 diabetes and obesity. It works by suppressing appetite, controlling blood sugar, and slowing digestion.

What are the differences between the types?

Ozempic and Wegovy fall under the semaglutide category. When branded as Ozempic, it’s indicated for those with type 2 diabetes. As Wegovy, it’s indicated for treating obesity.

Recently, Wegovy has also been indicated for heart disease prevention and for what was previously called “fatty liver” disease, which is now known as Metabolic dysfunction-Associated Steatotic Liver Disease or MASLD.

Next, we have Mounjaro and Zepbound, which have the same molecule, called tirzepatide. When branded as Mounjaro, it’s typically used to treat type 2 diabetes, and when branded as Zepbound, it’s indicated for treating obesity.

More recently, Zepbound has received an indication for treating sleep apnea, too.

Oral vs. Injectable

There are now oral forms of GLP-1s on the market.

The first one that came out is oral Wegovy. It’s the same medicine as the injectable, but in oral form. It has been shown in studies to be equivalent to the injectable Wegovy at the high dose.

There are restrictions on how oral Wegovy is taken, and if they aren’t followed exactly, it may not result in equivalent weight loss as the injectable form.

Oral Wegovy must be taken with a glass of water first thing in the morning. No other medications or drinks can be consumed during the 30 minutes immediately after taking them.

The other oral medication that came out recently is Foundayo™, and it doesn’t come with the same restrictions because it’s a slightly different molecule called orforglipron that is absorbed easier.

However, studies show that it provides a lower average weight loss than the injectables.

Side effects

When starting a GLP-1 or increasing the dose, the most common side effects can include nausea and vomiting; diarrhea; constipation; stomach pain, bloating, or gas; and heartburn or acid reflux.

Less common side effects include fatigue; headache or dizziness; decreased appetite; and injection site reactions, like redness, itching, or swelling.

To manage these symptoms, try eating smaller, more frequent meals. If you have diarrhea, avoid high-fiber and fatty foods. If you’re constipated, ensure you’re getting enough dietary fiber. And be sure to stay hydrated by drinking plenty of water daily.

When in doubt, contact your prescribing provider.

Choosing injection sites

GLP-1s are given subcutaneously, which means right under the skin where there’s some fat. The most common injection site is the stomach area, but people can also inject it in their thighs or the back of their arms. It really comes down to personal preference.

You want to avoid injecting in the exact same spot every single time. The injections could cause some irritation or injection-site reaction, so you want to move it around, but you don’t necessarily have to relocate it.

For example, if your stomach is your preferred site, move it around your belly button each time you give yourself an injection.

Once I start, can I stop?

That’s a great question. I will challenge that question, though, by saying it’s based on diet culture. We used to think that you go on a temporary diet, lose weight, and then you’re fixed.

We now know that’s not true. You must manage your eating lifelong. If you go on a temporary diet and lose weight but then go back to eating how you were eating before, you will gain weight back.

GLP-1s work by controlling the physiologic drivers of appetite and weight. Just like any other chronic disease you’re treating, you expect while you’re on the medicine for it to help.

If you’re treating high blood pressure, it’s going to lower your blood pressure while you're on it, and then when you stop, it’s not going to keep working.

Now, if you can keep eating the same amount, the same types of foods, it’s possible you won’t gain all your weight back. But the studies do show that as people stop the medicine, most do start to regain weight, generally because they are changing how they’re eating.

I know a lot of people don’t like the idea of staying on a GLP-1 forever. In our practice, we have people start weaning their dose to see if they’re able to maintain their weight at the lower dose. If that works, we’ll go a little bit lower, and we might keep lowering.

If some people can come off, that’s great. If they start to regain, we may need to restart at a low dose, or we could start a maintenance-type medicine.

Some of the oral GLP-1s may have a great role for helping people maintain, even if they weren’t the choice initially for taking the weight off.

How do I get started on this journey?

The best place to get started on any weight-loss plan is an appointment with your primary care provider, who can help you determine your goals and recommend safe changes to your eating and exercise habits.

At WVU Medicine Medical Weight Management, we offer a non-surgical, individualized program that addresses the physical, behavioral, and medical causes of obesity. It combines nutrition counseling, exercise planning, behavior change support, and medical management delivered by a multidisciplinary team.

We look forward to helping you achieve your goals.

For more information, visit WVUMedicine.org/WeightMgmt