Tirzepatide vs Semaglutide: Which Is Better for Weight Loss?

Tirzepatide and Semaglutide are medications primarily intended for managing Type 2 Diabetes, and are increasingly being used for weight management.¹ While some research shows that Tirzepatide may be more effective at achieving your weight loss goals, there’s substantial evidence to support Semaglutide’s effectiveness too. Both of these drugs work by reducing hunger signals to the brain, in the hope you then eat less food.¹

The research as to which is better is still inconclusive, however, each offers unique functions. It’s just about picking the right fit for you. 

In this article, you’ll learn the difference between Tirzepatide and Semaglutide, whether they have any side effects, which is most effective for weight loss, and what the current research says. 

What Are Weight Loss Drugs and Why Might You Need Them? 

Overweight and obesity is one of today's most prominent global health challenges and carries a significant disease burden. Overweight and obesity increases your risk of multiple conditions, including high blood pressure, Type 2 Diabetes Mellitus, non-alcoholic fatty liver disease, cardiovascular disease and cancer.¹ Research has shown that by reducing 5-10% of body weight has been shown to improve health outcomes and quality of life.

The main recommendation to lose weight is to modify dietary and lifestyle behaviors, however for some individuals this is challenging and doesn’t result in long-term weight loss. It often requires counting calories or having to heavily monitor food intake, which can be inconvenient due to its time requirements. There are also many fad diets available promising to help you lose weight that may not be evidence-based or effective.

To tackle this issue, pharmaceutical drugs such as Tirzepatide and Semaglutide are available to aid further weight loss. They work as an addition to a healthy and balanced diet and lifestyle.¹

What Is Tirzepatide? 

Tirzepatide is both a glucose-dependent insulinotropic polypeptide (GIP) and a glucagon-like peptide-1 (GLP-1) receptor agonist.² GIP is responsible for controlling appetite and reducing calorie intake,³ and GLP-1 causes the pancreas to release more insulin.²

When more insulin is released, the body can take more sugar from the blood and carry it into your cells, which reduces an individual’s overall blood sugar levels. Due to this action, the medication was first approved for the treatment of Type 2 Diabetes Mellitus. The joint action of GIP and GLP-1 means that Tirzepatide can reduce appetite by signaling to the brain that no more food is needed. This means the drug also works for weight loss.⁴

GLP-1 also supports the process of storing fat properly after eating, and how well fat tissue responds to insulin. This process helps to avoid the storage of excess fat in the wrong places in the body.⁵

What Are the Advantages of Using Tirzepatide? 

There are many advantages to using Tirzepatide. Firstly, it’s an injection that only needs to be administered once per week,⁶ which means you’re more likely to comply with its use.

Research also shows it’s effective for both weight loss and managing Type 2 Diabetes, as it can improve hemoglobin A1C levels, which are markers of blood glucose. For people that have Type 2 Diabetes and have been told to lose weight to help manage their blood sugar control, Tirzepatide is a great way to improve overall health outcomes and disease management.⁵

Tirzepatide is also convenient, as it can be given with or without meals, at any time of the day. This differs from other weight loss medicines such as the pill form of Semaglutide, which has to be administered 30 minutes before the first food of the day.⁷

When compared with Semaglutide in clinical trials, Tirzepatide also often produces better results for weight loss and reducing blood glucose levels.⁵

Other weight loss drugs are also typically associated with liver toxicity, however clinical trials have shown that Tirzepatide doesn’t carry this risk. Given its weight loss properties but lack of impacts on the liver, it’s also likely to play an indirect role in the treatment of nonalcoholic fatty liver disease (NAFLD). However, further research is needed before this can be an approved drug for NAFLD.²

What Is Semaglutide? 

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist just like Tirzepatide, so the drug works in a similar way. However, it doesn’t activate the GIP hormone receptor like Tirzepatide, so it doesn’t have this double weight loss action.

Semaglutide still works by mimicking the GLP-1 receptor, which is produced by your gut after you eat food and signals to the brain that you're full.⁷

Semaglutide carries many of the same advantages as Tirzepatide, such as its use in Type 2 Diabetes Mellitus and effectiveness for weight loss, however, it’s also available as oral tablets and an injection. For some people, having different options to take medicine will increase their compliance.⁸

What Are the Advantages of Using Semaglutide? 

Many research papers show that Semaglutide is a safe and effective treatment for weight loss.⁸

Semaglutide has been on the market for a long time. This means it’s been researched thoroughly and there’s a large base of clinical evidence available on it to make an informed choice as to whether it’s right for you. There’s robust research on its efficacy for lowering blood glucose levels and managing risk of Type 2 Diabetes Mellitus. 

Research also shows that taking Semaglutide significantly reduces risk of cardiovascular conditions such as cardiovascular disease, heart attack and stroke.⁹ The latest research also shows that Tirzepatide significantly reduced the long-term risk of atherosclerotic cardiovascular disease among those overweight or obese without diabetes.¹⁰

Like Tirzepatide, Semaglutide appears to be safe when used concurrently with metformin or insulin¹¹ which are commonly used drugs for Type 1 and Type 2 Diabetes Mellitus. While Semaglutide doesn’t appear to have hypoglycemia risks, those on insulin or sulfonylurea should still seek medical advice to ensure optimal safety.⁸

Due to having a tablet form available, this drug is also much better suited for those with needle phobia.¹²

Are There Any Side Effects of Using These Weight Loss Drugs? 

Like all drugs, there may be some side effects to using either Tirzepatide or Semaglutide.

Because these two weight loss drugs have to be injected, this can be uncomfortable for some people, particularly those with needle phobias (unless one opts to use oral Semaglutide, but there’s no oral version of Tirzepatide).

Research has also shown that both Tirzepatide⁵ and Semaglutide¹³ may cause thyroid C-cell tumors. It’s important to tell your doctor if you have a family history of thyroid cancer or a condition called Multiple Endocrine Neoplasia syndrome, which causes tumors to develop on endocrine glands. If you’re taking Tirzepatide or Semaglutide and are noticing abnormalities to your neck or thyroid such as swelling, a lump, difficulty in swallowing, hoarseness or shortness of breath, it’s important to notify your doctor immediately.

While oral administration of Semaglutide doesn’t diminish the glucose- or weight-lowering efficacy of the drug, both oral and injectable versions have been associated with adverse reactions. Some of these are gastrointestinal symptoms such as nausea, abdominal pain, and vomiting, which can also occur with Tirzepatide.¹⁴ Research has however shown that these symptoms usually subside within 2 weeks of treatment initiation for Semaglutide.⁹ While more research is needed, these gastrointestinal effects with Tirzepatide are expected to decrease slowly over time as your body adjusts to the medication.¹⁵

One study showed that Tirzepatide can cause hypoglycemia without being on another glucose-lowering medication.¹⁶ It’s always important to ensure your prescribing practitioner is aware of your full medication profile.

Let’s Weigh Up the Differences 

Tirzepatide and Semaglutide are both used to help patients with Type 2 Diabetes and weight loss, and they can both improve cardiovascular health. The main difference between these medications are that they have two different mechanisms of action, meaning they work slightly differently.

Tirzepatide is the only medication that targets both the GIP and GLP-1 receptor agonists, and therefore it works in a different way to Semaglutide by activating both these receptors.

However, while Semaglutide only targets one receptor, there’s much more research and evidence available on its efficacy as it has been available on the market for much longer. Therefore, you may be able to make a more informed choice about Semaglutide as it’s more well-understood.

Tirzepatide and Semaglutide are both available as injections, however, Semaglutide has an oral tablet option, as well as a sublingual option (which is placed under your tongue) which has some strict requirements for administration. It must be administered at least 30 min before the first food, beverage, or oral medication of the day, and it needs to be taken with no more than 4oz of plain water only.¹¹

How Compounded Medications Help Keep the Cost Down

At Henry Meds, Tirzepatide and Semaglutide are compounded, meaning the doses are tailored to your needs.¹⁷

Henry Meds’ trained team of specialists will help you decide which compounded formulation is best for you, based on your individual circumstances. For instance, your medication’s dosage can be adjusted to levels that are appropriate for your case.

Since Semaglutide¹⁸ and Tirzepatide¹⁹ have gained significant prominence in the weight loss world,  they’re extremely sought-after. This means they’re challenging to locate, and even when available, their steep prices make them inaccessible for many individuals. Thankfully, medications such as Compounded Semaglutide and Compounded Tirzepatide address this problem as they contain the same active ingredients without the brand-name prices. 

Compounded Semaglutide and Compounded Tirzepatide come at a fraction of the cost compared to the most popular brand-names and do not face supply shortage concerns. 

You can read more about compounded medicines and sign up to Henry Meds by clicking here. 

Please note: Henry Meds doesn’t offer Ozempic® or Wegovy®, which are only available from the Novo Nordisk company. Compounded Semaglutide is a patient-specific medication created in a state Board of Pharmacy or FDA licensed compounding facility per a prescription from a licensed healthcare professional. Compounded drugs are required to exclusively use ingredients from FDA-licensed facilities, and test sterile compounds for potency, sterility, and purity. While compounded drugs are legal they do not undergo pre-market approval from the FDA as they are not made in large batches for the public, compounds are made based on specific orders from a medical professional. Because of that the dose, route of administration, safety, and efficacy may differ from commercially available, brand-name, drugs. Henry Meds exclusively works with licensed sterile compounding pharmacies in the United States. 

Please note: Henry Meds doesn’t offer Mounjaro® or Zepbound®, which are only available from the Eli Lilly company. Compounded Tirzepatide is a patient-specific medication created in a state Board of Pharmacy or FDA-licensed compounding facility per a prescription from a licensed healthcare professional. Compounded drugs are required to exclusively use ingredients from FDA-licensed facilities, and test sterile compounds for potency, sterility, and purity. While compounded drugs are legal they do not undergo pre-market approval from the FDA as they are not made in large batches for the public, compounds are made based on specific orders from a medical professional. Because of that the dose, route of administration, safety, and efficacy may differ from commercially available, brand-name, drugs. Henry Meds exclusively works with licensed sterile compounding pharmacies in the United States. 

To help you trust the information we provide, every article written by Henry relies on peer-reviewed studies and medically-reviewed facts. We ensure that data, ideas, and figures cited are reliable, current, and accurate. Our team of medical reviewers aim to help you cut through the noise with clear and authoritative primary and secondary sources.

Nothing in this article is intended to be prescriptive or medical advice. Talk to your doctor before starting a new diet and exercise plan. Information presented is about our medically supervised weight management programs and is not an advertisement for a specific drug.