A Comparison of Tirzepatide (Zepbound) vs. Semaglutide (Ozempic/Wegovy) from a Weight Loss Expert

balancing rocks on a beach with background imagery of weight loss injectable medications, nutrition and cost of weight loss medications

Zepbound by Eli Lilley was recently the first GLP-1/GIP medication FDA-approved for weight management. Although this is exciting, is this really a new drug, or just a “repurposing” of an existing drug? Let’s find out.

Medications for Weight Loss vs. Diabetes 

Zepbound (or Tirzepatide) is the exact same medication that is found in the popular medication approved for diabetes called Mounjaro. Mounjaro was found to have 22.5% weight loss at the highest dose vs. placebo in patients taking it for diabetes which is remarkable. This is almost 8% higher than GLP-1s alone. The problem Eli Lilley has is this: 22.5% weight loss will reverse most type II diabetes and put a company specializing in drugs for diabetes out of business. For this reason, Tirazepide was remarketed as Zepbound and eventually approved by the FDA for weight management. 

Interestingly, Novo Nordisk did the same thing with Semaglutide. It was released in 2014 as Ozempic, a once-weekly injectable used for type II diabetes only. In 2021, Semaglutide was approved for weight loss under the trade name Wegovy. At the highest doses, Semaglutide boasts a 15% weight loss compared to placebo which doubles previous injectables but is still not as good as Tirzapetide.

The approval of Zepbound for weight loss is great news for patients because there is now a pathway forward for coverage of this medication for those without diabetes who need weight management. Many of my patients have found success on Mounjaro through their coupon program, which was rapidly withdrawn recently. This answers the question, “What do I do now?”

Cost of Tirzepatide vs. Semaglutide

The price for Tirzepatide without coverage can run as high as $ 1,400-$ 1,500 per month which is prohibitive for most users. Compounding pharmacies have been approved to offer Tirzepatide due to a shortage at about half the cost, and are offered at some weight loss practices but supply has remained a moving target. If insurance companies choose to cover (which has yet to be determined), the cost will likely be considerably less and may just involve a copay. It is important to understand that plans have to opt into covering weight loss medications, so it is important to review coverage of this class with your insurance company and ask about the topic during open enrollment. 

Semaglutide is considerably cheaper. It is still high if not covered for brand (about $1,000- $1,200) however, compounded is much less – usually $300- $ 500 per month.  

Note: If you find these drugs for much cheaper and there is not a physician involved in your treatment, I would be very leery of the safety and efficacy of what you are purchasing. It is also important to have a nutrition plan involved with regular check-ins. These medications are very powerful and at high doses many patients forget to eat which can be very dangerous. There are several pop-ups appearing on the streets and online. I have seen some real disasters from the programs. Please watch for the signs and stay away. 

How to Get a Hold of Weight Loss Medications like Tirzepatide and Semaglutide

Accessibility of Tirzepatide and Semaglutide have been moving targets. We are at an unprecedented time in medicine, with weight management drugs being among the worst when it comes to shortages at varying doses. This is a real problem for this class, because you must work up on these drugs slowly. If you start and stop and restart at a high dose (because that is the only one you have access to) you will get very sick. I don’t see any of these supply issues ending any time soon, unfortunately, and it has become a real factor in prescribing these drugs to our patients.  

How Does Tirzepatide Work Differently From Semaglutide for Weight Loss? 

Semaglutide (Ozempic and Wegovy) and Tirzapatide (Mounjaro and Zepbound) are all medications that fall under the category of GLP-1 receptor agonists. This class of medications has been around since 2005. Today, we have a significant amount of data to prove both class safety and efficacy. 

GLP-1 receptor agonists promote fullness by triggering GLP-1 receptors (fullness receptors) in the brain and the gut. They also decrease gastric emptying (how fast the food moves through your stomach) which also causes fullness.

Tirzapetide (Mounjaro and Zepbound) also contains a GIP receptor agonist in addition to a GLP-1 receptor agonist. We do not know much about the GIP receptor, other than being told it is also a receptor that promotes satiety. Through my patients, I have also found that it helps addictions to food, gambling, alcohol etc. in addition to boosting mood which I did not expect. This is good when there is ample supply, but bad when one has to start and stop a dose due to supply issues. This definitely plays a role in my prescribing practices. 

Balancing Weight Loss Success with Supply Chain Challenges

Injectable AOMs (anti-obesity medications) have been a wonderful addition to my weight loss practice, however, the supply chain issues are a game changer.  When there is ample supply I will use them, but I will always have a backup plan. When there isn’t, I will stay with the old tools that worked great before, during, and after the media frenzy and chaos with this class of medications. I have seen patients do very well with weight loss and an overall sense of well-being with injectables, only to suffer greatly when the supply dwindles. There has been a complete lack of empathy from both the pharmaceutical industry and insurance companies on these issues, leaving both patients and physicians stumbling to find a resolution. 

The approval of Zepbound could be great for patients if it is covered by the insurance companies and that coverage remains. Again, this is a great class of medications to help with weight loss! There is a risk of starting them however for both physicians and patients, as there is no guarantee month to month that patients will have their refills.  

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