Throwdown! semaglutide vs. tirzepatide

Posted: Apr 14 in Weight Loss Medication by Dr. Lazarus

There are two new heavyweights (? lightweights) in town duking it out to help people lose weight and keep it off: semaglutide and tirzepatide. How do semaglutide and tirzepatide for weight loss stack up?

How do semaglutide and tirzepatide work?

In the early 1990’s, scientists observed that there was a toxin found in Gila monster saliva which caused its prey to develop low blood sugars (hypoglycemia), making them an easy, tasty treat! The toxin resembled glucagon, a hormone that raises blood sugar, so, scientists named it glucagon-like-peptide 1, or “GLP-1.” In the early 2000’s, we got our first medical breakthrough with GLP-1, a drug called exenatide (Byetta) approved for the treatment of type 2 diabetes.

Through the years, GLP-1’s have improved – after exenatide (Byetta), we saw liraglutide (Victoza / Saxenda), dulaglutide (Trulicity), semaglutide (Ozempic / Wegovy), and tirzepatide (Mounjaro / Zepbound). Decades of research has shown these drugs to be safe and effective treatments for type 2 diabetes. Prior to these medications, most diabetes medications caused weight gain. But these drugs caused weight loss, and research was showing improvements in other conditions including reduction in the risk of heart attacks and strokes.

This led to research in the use of liraglutide, semaglutide and tirzepatide for the purpose of chronic weight management. Liraglutide, marketed as Saxenda, was our first GLP-1 approved for weight loss. Next was semaglutide, marketed as Wegovy for weight management, and as Ozempic and Rybelsus for diabetes, and then tirzepatide, marketed as Zepbound for weight management, and as Mounjaro for diabetes.

These GLP-1 hormones work by telling the brain that the body is in a fed, or “sated” state. We have learned that weight loss triggers hunger in part by lowering levels of this and other hormones. So, in effect, the GLP-1’s replace a hormone that gets low when people try to lose weight, thus allowing for sustained weight loss without the person feeling hungry all the time.

Round 1: Dosing

Both semaglutide (Wegovy) and tirzepatide (Zepbound) are self-administered injections approved for chronic weight management given once weekly. Each comes in a pre-filled pen that is simple to use.

Wegovy comes in 5 strengths – .25, .5, 1, 1.7 and 2.4 mg. However, only the 1.7 and 2.4 mg are approved for chronic weight management, while the first 3 doses are for titration only. The diabetes version, Ozempic, comes in multi-dose, multi-use pens which can deliver doses as low as .25 mg weekly and as high as 2 mg weekly.

Zepbound comes in 6 strengths – 2.5, 5, 7.5, 10, 12.5, and 15 mg. The 2.5 mg dose is for initiation, but the remaining doses can be used for chronic weight management.

Winner: TIE

Round 2: Effectiveness

Modern studies looking at the effectiveness of anti-obesity medications look at the percentage of body weight lost after a year of treatment with a particular dose of the medication. Further, they look at the percentage of those treated achieving 5%, 10%, 15%, and 20% or more of the total body weight.

So, how do they stack up? To keep this simple, let’s just focus on the percent of total body weight lost.

Winner: tirzepatide / Zepbound

Round 3: Side Effects

All GLP-1 medications have similar side effects. With semaglutide and tirzepatide, many people experience nausea, diarrhea, constipation, heartburn and other gastrointestinal side effects. Other side effects can include fatigue, headache, hair loss, vomiting and burping. Less common but more serious adverse events include pancreatitis and gallbladder attacks.

Side effects are usually mild to moderate, and in the clinical trials more than 90% of those treated with semaglutide / Wegovy and tirzepatide / Zepbound were able to stay on the medications. Side effects tend to subside as the body gets used to the medication.

In our clinical experience, tirzepatide seems to cause less side effects than semaglutide.

Winner: tirzepatide / Zepbound

Round 4: Health Improvements

Both semaglutide / Wegovy and tirzepatide / Zepbound are very effective weight management solutions. In their clinical trials, Ozempic / Wegovy have been shown to reduce the risk of a recurrent major adverse cardiac event (heart attack / stroke) by 20% over 5 years. Semaglutide has also shown benefits for people living with chronic kidney disease and congestive heart failure.

It is possible that tirzepatide / Zepbound has these same benefits; however, we will not have information on heart risk reduction until ~2027.

Winner: semaglutide / Wegovy

Round 5: Cost

At the time of this article, cash prices at pharmacies are as follows:

Ozempic: ~$900 / month
Wegovy: ~$1,500 / month

Zepbound: ~$1,100 / month

Ozempic is not covered by insurance if used for weight loss, but because of the way the pen is manufactured, it is possible to get 8 doses out of 1 pen, albeit at a lower dose than those found in Wegovy.

Both Wegovy and Zepbound have manufacture-sponsored coupons that can save people who qualify around $500 / month. However, certain insurers such as Medicare do not allow the use of these coupons.

Many insurers now cover Wegovy and Zepbound for weight loss. When covered, the cost is typically around $25 / month for either medication.

And, Medicare has announced for people with obesity or overweight at risk for a recurrent myocardial event, they are going to now allow coverage for medications which lower heart risk, which at this time, only includes Wegovy.

Winner: TIE

Availability

Both semaglutide and tirzepatide are highly sought after medications. There have been frequent shortages of semaglutide, although at this time, Ozempic appears to be well-stocked, and the higher doses of Wegovy are stable.

Tirzepatide was stable until a few weeks ago when most local pharmacies were unable to find it for a few weeks.

We do not know what the future will look like, but for now, it is possible that people will be discontinued on their medication, whether semaglutide or tirzepatide, while the manufacturers ramp up supply to try to meet this unprecedented demand.

Winner: TIE

So, who wins the semaglutide vs. tirzepatide throwdown?

Well, as you can see, there are far more similarities than differences. For most people, the best medication will be one that is in stock at the pharmacy, cost-effective, and covered by insurance. But, if you have access to both, we would recommend the following:

If your health would benefit from the higher percentage weight loss (15-20%) of Zepbound / tirzepatide, and you have not had a cardiac event, Zepbound offers modestly more weight loss with fewer side effects.

However, if you are high risk for heart disease, have had a heart event or the equivalent (stroke, stent), or do not require 15-20% weight loss, semaglutide / Wegovy may be a better choice.

And, if you do not have coverage for GLP-1 medications, remember that there are many safe, effective and affordable oral medications available as well.

-Ethan Lazarus, MD, FOMA