In diabetes and weight management, tirzepatide and semaglutide stand out as being two of the most effective treatments available. When following clinical guidelines and standard titration timelines, unparalleled results can be achieved. Both are GLP-1 receptor agonists, but they each have specific features, outlined below.
Think about both of these as highly effective tools to both control blood sugar levels and maintain a healthy body weight. Semaglutide works like the hormone GLP-1 (glucagon-like peptide 1). It helps the body make insulin and reduces appetite. Tirzepatide takes this mechanism of action a step further by activating both GLP-1 and GIP receptors. This dual action improves insulin release and lowers the amount of sugar made by the body. As a result, it can lead to a greater % of weight loss.
GLP-1 receptor agonists, like tirzepatide and semaglutide, have changed the way we manage weight. They help our bodies control hunger and metabolism. These medicines act like GLP-1, which is a hormone produced in the gut. This hormone plays a key role in managing how much we eat and keeping our blood sugar levels stable.
When you eat, GLP-1 sends messages to your brain to tell you that you are full. This helps reduce your desire to eat. It also causes your stomach to take longer to empty. This way, you are satisfied quicker and feel satiated for longer. As a result, you take in fewer calories, which directly contributes to weight loss, of course. GLP-1 receptor agonists boost these effects inherently so that you’re not relying solely on willpower to “stick to a diet” while in a large caloric deficit.
These medications change how the body uses energy and stores fat, resulting in a larger calorie deficit and greater body fat loss over time. When compared to traditional weight loss protocols, their unique method of weight management makes GLP-1 receptor agonists a must-consider for anyone who wants to achieve and sustain a healthy body weight over time.
As mentioned earlier, tirzepatide and semaglutide both work on the GLP-1 receptor. However, tirzepatide can lend enhanced effects as it also acts on the GIP receptor. Because of this, it improves how the body manages insulin and controls blood sugar levels to a greater degree than semaglutide.
Analogy: semaglutide is like a key. It helps control blood sugar levels and supports weight loss. Tirzepatide, then, could be considered more of a “master key”. It helps with blood sugar control and weight loss, but it can also improve metabolic processes for even greater results.
Tirzepatide has two main effects. First, it helps the body produce more insulin. Second, it slows down the movement of food from the stomach. This means you feel full longer. Because of this, you eat less, which can lead to substantial weight loss. It also changes how the body uses and stores fat, helping to improve metabolism.
This action goes both ways, making tirzepatide a good choice for managing (and potentially preventing) type 2 diabetes and obesity. It works naturally with the body by stimulating endogenous processes. I’ll outline this below.
As a receptor agonist, semaglutide binds to GLP-1 receptors in the pancreas. This allows the pancreas to release adequate insulin when blood sugar levels increase. This process helps to lower blood sugar levels and keep them at a healthier level, reducing insulin resistance over time.
As with any new medication, it is important to highlight possible side effects. Semaglutide and tirzepatide both can lend to gastrointestinal (GI) side effects.
The most common side effects of GLP-1 usage are nausea and indigestion, and potentially diarrhea and constipation. These effects are usually mild and often go away as your body gets used to the treatment. It is important to talk about nutrition and physical activity with your healthcare provider while you are in treatment. Both of these can help manage and reduce the aforementioned side effects.
Most of the time, the above side effects are not serious. They usually improve (and even disappear) as your body adapts to the medicine. However, other side effects can occur, but are much more rare. These can include pancreatitis, problems with the gallbladder, and very low blood sugar (hypoglycemia). Hypoglycemia is especially important to be aware of if you take tirzepatide with other diabetes medications, which should only be done under the guidance of the same provider so that they can adjust dosages of all of your diabetes medications together, as needed.
There is a concern about a greater risk of thyroid tumors, like medullary thyroid carcinoma (MTC), in those with a family history. Most of this information comes from studies on animals, so we do not completely know how it affects humans. If you or your family have a history of MTC, Multiple Endocrine Neoplasia syndrome type 2 (MEN2), or other health conditions related to the thyroid, it is very important to discuss this with your provider before beginning GLP-1 treatment.
Both tirzepatide and semaglutide are taken as once-per-week, subcutaneous injection. The convenience makes it easy to stay on top of your treatment regimen and fit it into your weekly routine. There is also an oral version of semaglutide, Rybelsus™, that is taken daily, though often can have an increased risk of gastrointestinal side effects and less efficacy in regards to weight loss.
The typical starting dose is 2.5 milligrams per week. This dose increases under your provider’s discretion, typically every 4 weeks, depending on how your body is responding to the medication. This helps your body adjust to the medicine and mitigate gastrointestinal (GI) side effects.
Your healthcare provider will monitor how the medicine affects you and titrate accordingly. Here is the standard titration table for tirzepatide that we use at Fella:
2.5mg - Month 1
5mg - Month 2
7.5mg - Month 3
10mg - Month 4
12.5mg - Month 5
15mg - Month 6+
Your provider will ultimately determine when to increase your dosage (it may not always be monthly depending on results + side effects). Some patients will find that 7.5mg works just fine, and never need to go beyond that. Others will experience minimal results at first, and end up titrating to 15mg/wk by the 6 month mark before they start seeing substantial results.
The typical starting dosage of semaglutide is .25mg taken subcutaneously once per week. If you’re taking the oral formulation of semaglutide, your starting dosage will be a 3mg tablet taken 1x daily for the first 30 days.
As with tirzepatide, semaglutide will be tapered up under your provider’s discretion, with a standard 4 week titration timeline per dosing increment. With brand name Ozempic™, the highest dose is 2mg, while with Wegovy™ it is 2.4mg. One of the benefits of using compounded semaglutide (the active ingredient in both Ozempic™ and Wegovy™) is that you may have 6 standard titrations, outlined here:
.25mg - Month 1
.5mg - Month 2
1mg - Month 3
1.7mg - Month 4
2mg - Month 5 (Ozempic™ highest dose)
2.4mg - Month 6 (Wegovy™ highest dose)
There are two brand name medications with the primary active ingredient semaglutide + two brand name medications with the primary active ingredient tirzepatide.
Brand name options:
Tirzepatide = Mounjaro™ (T2 diabetes) + Zepbound™ (weight loss)
Semaglutide = Ozempic™ (T2 diabetes) + Wegovy™) (weight loss)
Unfortunately, out-of-pocket costs for these are often out of reach for the average American, hovering in the ~$1000/mo range (and beyond with higher dosages). Insurance coverage for these drugs is scarce also, which has led to more-and-more Americans turning to compounded GLP-1s instead. Approximately 1 in 8 adults in the US have taken a GLP-1 medication at the time of writing (Oct 2024).
Compounded medication is produced by FDA-registered, US-based compounding facilities and provides a more cost-effective solution for individuals interested in exploring GLP-1 medications without having to pay high out-of-pocket costs.
At Fella Health, we believe choosing the right medicine for your health is a decision that you should have a role in, alongside your healthcare provider. Tirzepatide and semaglutide are both fantastic choices for treating type 2 diabetes and obesity, and we’ll do a thorough (yet convenient) medical review prior to starting you on your desired treatment. Tirzepatide has shown greater efficacy than semaglutide, without an increase in side effects; so, if you’re looking to lose a larger % of bodyweight, it may be worth considering tirzepatide initially.
Talk openly about your health goals and health history, first and foremost. Here are some good prompts to take into consideration and then discuss with your provider: do you want to control blood sugar, lose weight, or both? How much weight are you looking to lose? Are you pre-diabetic, T2 diabetic, T1 diabetic? Do you have a family history or a history yourself of pancreatitis, gastroparesis, thyroid carcinoma?
Additionally, share any concerns you have about side effects (gastrointestinal) or how to self-administer a subcutaneous injection.
Think of looking your health journey as a team effort. Your healthcare team has a lot of knowledge, but the impact of your input cannot be understated, and so it’s important to share feedback on your treatment frequently. Working in conjunction with your healthcare team will often yield the greatest results and ensure that you’re able to manage your side effects.
When thinking about Tirzepatide and Semaglutide for your treatment, consider their benefits, side effects, and the associated cost. If you don’t have insurance coverage, for example, compounded GLP-1s may be the best fit for you. It is important to speak with your healthcare team prior to starting treatment, as well as understand where your medication is being sourced from. By staying informed and working with your provider, you can feel sure about making a choice that fits your needs and helps you achieve your health goals.
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Semaglutide and tirzepatide are once-weekly medications prescribed to help people manage their weight and blood sugar. They belong to a class of medications known as GLP-1 receptor agonists, and work by acting like natural hormones in the body associated with the digestive process. They can help patients achieve lower, more table blood sugar levels and achieve significant decreases in bodyweight.
Yes! You can switch from semaglutide to tirzepatide or vice-versa. There are clinical trials that have explored these changes, determining that it is safe to do so. However, it is important to talk to your healthcare provider and make the switch under their guidance and with their support.
Clinical studies show that tirzepatide can help people lose more weight than semaglutide. However, choosing which weight loss drug is "better" depends on your personal needs, including financial considerations if paying out-of-pocket. Your medical history and how your body responds to the treatment are both important to consider as well.
The choice to change from semaglutide to tirzepatide depends on your own situation. You must talk to your healthcare provider before making the switch. They will look at how well semaglutide has worked for you over the course of your treatment. They will also consider how much weight loss you want and any side effects you might have. They will check other health conditions, too, to ensure side effect risk is mitigated. For many who were struggling to lose weight on semaglutide, switching to tirzepatide helped accelerate their rate of weight loss.
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