JAMA Finds Tirzepatide More Effective Than Semaglutide in Head-to-Head Study
Tirzepatide is found more effective at weight loss than semaglutide in recent study
Just as obesity rates have increased in the United States, so too has the usage of semaglutide for weight loss. Over the last few years, injectable medications like Ozempic®, Wegovy® and Rybelsus® have gained popularity for their weight reduction capabilities. However, another weight-loss drug, known as tirzepatide, is beginning to stand out and may offer even greater results. Thanks to a new study released by JAMA, people are now asking, “Is tirzepatide better than semaglutide?”
Below, we’ll explore how these medications differ and discuss the new JAMA study that reveals which one might be the most effective.
Semaglutide for weight loss
Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA), but what does that even mean? To better understand, let’s break it down.
GLP-1 is a multifaceted hormone that reduces blood sugar levels, decreases inflammation, suppresses appetite and slows gastric emptying. Although this hormone is naturally produced in the small intestine, it degrades quickly due to the enzyme dipeptidyl peptidase-4 (DPP-4). However, semaglutide, a synthetic version of the GLP-1 hormone, is less likely to break down and has a longer duration of action.
As a receptor agonist, semaglutide mimics the actions of the GLP-1 hormone when it binds to a specific receptor in the brain. So when people take the medication, they experience weight loss because they feel full longer and don’t become hungry as often.
A 2021 study was done on almost 2000 participants who identified as overweight or obese, and over half of those taking semaglutide lost 15% to 20% of their body weight over 68 weeks.
Tirzepatide for weight loss
While semaglutide mimics the GLP-1 hormone, tirzepatide activates both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors. Also known as Zepbound™, it's the first dual GLP-1/GIP receptor co-agonist for treating type 2 diabetes and weight loss in the United States, Europe and the United Arab Emirates.
Since we already clarified what the GLP-1 hormone can do, let’s explore what’s so special about GIP.
GIP is occasionally referred to as the “obese hormone” because it aids the breakdown of fat in adipose tissue. But where this hormone really stands out is its role in regulating energy balance. GIP has the ability to boost energy expenditure and reduce energy intake.
With tirzepatide being a dual agonist, some have found it to be more effective at weight loss than its predecessor, semaglutide.
For example, participants taking tirzepatide during a 2022 clinical trial and who were considered overweight or obese had average weight reductions of 19.5% and 20.9% over 72 weeks.
Is tirzepatide better than semaglutide?
In early July 2024, a cohort study was published in JAMA that reviewed how weight loss differs between patients receiving tirzepatide and those taking semaglutide.
The participants included adults diagnosed as overweight or obese receiving semaglutide or tirzepatide between May 2022 and September 2023. They were identified using electronic health record (EHR) data from various United States healthcare systems. 41,222 patients met the study’s inclusion criteria, but only 18,386 remained after propensity score matching.
The study found that approximately 82% of participants taking tirzepatide experienced 5% or greater weight loss. In comparison, just 66.5% of participants taking semaglutide experienced this same level of weight loss. Researchers also discovered the following:
Achieved a weight loss of 10% or better: 62.1% (tirzepatide) vs 37.1% (semaglutide)
Achieved a weight loss of 15% or better: 42.3% (tirzepatide) vs 18.1% (semaglutide)
While both medications can aid weight reduction, tirzepatide has shown better weight loss results than semaglutide in this head-to-head study. However, that doesn’t mean tirzepatide is the best medication for everyone looking to lose weight.
Should everyone be taking tirzepatide instead?
Although research has revealed that tirzepatide is better for weight loss, it doesn’t mean that we should put semaglutide on the back burner. Both are effective, have no difference in gastrointestinal adverse event risks and can lead to significant weight loss.
Factors that include comorbidities, reactions to side effects and dosing can influence the type of medication prescribed or if the patient even qualifies for GLP-1s. It’s important that healthcare organizations prescribing GLP-1s for weight management offer follow-up appointments to manage the treatment.
How to decide which weight loss medication to prescribe
Determining which medication is best for patients ultimately depends on their goals and current health status. Clinics and providers also need to consider which medication is available due to the current shortages. Ozempic, for example, is expected to be in limited supply for the rest of 2024. Tirzepatide has been on the FDA’s drug shortage list since 2022. This shortage impacts those with type 2 diabetes who need it to manage their condition.
You must also determine if their insurance will cover one of these weight-loss medications. If an individual hasn’t met their deductible or doesn’t qualify for a savings card, they may have to pay the total cost of the drug. A carton of Zepbound starts at $1,034, and Ozempic is nearly $950 and up. In short, neither is cheap (especially for the uninsured), leaving many people priced out of the market.
In order to make up for the shortage of branded GLP-1s like Ozempic and Zepbound, compounded versions of the medication have also been made available via FDA licensed compounded pharmacies. These can prove to be much more affordable out of pocket, but likely won’t be covered under insurance.
Lifestyle changes can improve results
No matter which weight loss medication is selected, patients should be encouraged to incorporate exercise, follow a healthy diet and consider behavioral therapy. However, many people aren’t sure what that looks like. Fortunately, telemedicine weight loss programs are a great option for busy individuals who want support and ongoing intervention.
In addition, many patients tend to regain weight once they stop taking weight-loss drugs, but lifestyle changes guided by weight loss programs may be able to minimize this effect.
Weight loss medications may improve health outcomes
It’s known that there are many health risks associated with carrying excess weight, such as high blood pressure, heart disease, stroke and more. We also know that losing weight is associated with improved health outcomes. Weight loss medications like semaglutide and tirzepatide have been shown to be highly beneficial for some.
Additionally, when paired with telemedicine solutions, you can monitor patients easier and provide them with the continuity of care they need to succeed. So, if that’s something you’re interested in offering, you’re at the right place.
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