Tirzepatide Injections for Weight Loss – How Does it Work, Dosage and Side Effects

Peter Williams

Tirzepatide Injections for Weight Loss

With obesity rates continuing to rise globally, weight management remains one of the most challenging aspects of modern healthcare. Many people who are overweight or obese are unable to turn things around via diet and exercise alone, creating a huge demand for effective weight management treatments.

Many of the best options are injectable medications that were originally developed to help type 2 diabetics manage their blood sugar levels. This is certainly the case with Tirzepatide.

The FDA approved Tirzepatide as a treatment for diabetes in May 2022. Since then, it’s been distributed under the Mounjaro brand name. One of the most common Mounjaro side effects is weight loss so doctors often prescribe Mounjaro “off label” as a weight loss shot.

In November 2023, Tirzepatide gained FDA approval as a weight loss medication under the Zepbound brand name. Although there is no difference between Mounjaro and Zepbound, one medication is only approved for treating diabetes, while the other only has approval for weight loss.

Tirzepatide Summary

Tirzepatide is a medication used primarily for managing type 2 diabetes. It’s a relatively new injectable drug that works in a unique way. Unlike other diabetes medications that typically target just one aspect of the disease, tirzepatide combines the actions of two different hormones that are naturally found in the body. These hormones are called GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide).

Here’s how tirzepatide works in simpler terms:

Helps produce insulin: When blood sugar levels rise, tirzepatide stimulates the pancreas to release insulin, a hormone that helps lower blood sugar levels by allowing sugar to enter the body’s cells.

Reduces sugar production: It tells the liver to reduce the amount of sugar it releases into the bloodstream, which is important because having too much sugar in the blood is a key problem in diabetes.

Slows digestion: By slowing down how quickly the stomach empties after eating, it helps prevent blood sugar levels from rising too quickly after a meal.

Reduces appetite: It can help a person feel fuller longer and less hungry, which can lead to eating fewer calories and potentially losing weight.

Because of its effects on blood sugar control and appetite, aside from its use in diabetes management, tirzepatide is also being researched for its potential to help with weight loss in people with obesity. It’s important to note that tirzepatide requires a prescription and should be used under the guidance of a healthcare provider.

Discovery and Development of Tirzepatide

Tirzepatide’s creation is the result of research into the the activity of intestinal hormones called incretins and their role in enhancing insulin secretion after meals. Two hormones quickly became focal points for diabetes research—glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).

Companies such as Novo Nordisk, a Scandinavian pharmaceutical company, successfully developed anti-diabetic and weight management drugs that work by mimicking the abilities of GLP-1. The FDA has approved several GLP-1 receptor agonists for use in both roles.

Eli Lilly and Company, an established pharmaceutical giant, based in the US, went a step further by creating a drug that mimics the actions of both GLP-1 and GIP and GLP-1. Tirzepatide is the result. It is the only dual agonist medication that has gained the approval of the FDA.

Preclinical Studies and Clinical Trials

Before tirzepatide became available via pharmacies, it underwent rigorous preclinical studies. The results were promising, showing significant glucose-lowering effects and weight loss in animal-based studies. 

Data from Phase I and II clinical trials shows the drug was just as effective for humans. The data also shows that tirzepatide’s abilities are superior to those of single-action drugs, like semaglutide, which are only capable of mimicking GLP-1.

 The encouraging data paved the way for Phase III trials. This stage in a new drug’s development is crucial for determining its safety profile and efficacy and helping it through regulatory approval processes.

Surpassing Expectations: The SURPASS Program

The SURPASS program, a comprehensive series of Phase III trials, was designed to evaluate the safety and efficacy of tirzepatide in a broader patient population. The results were nothing short of remarkable, with tirzepatide consistently demonstrating superior glycemic control and significant weight reduction compared to other diabetes medications.

Furthermore, tirzepatide displayed a favorable safety profile, with gastrointestinal symptoms being the most commonly reported side effects. These findings solidified tirzepatide’s position not only as a potent antidiabetic medicine but also as a potential weight management drug.

FDA Approval and the Path Forward

Following the success of the SURPASS trials, tirzepatide received FDA approval for the treatment of type 2 diabetes. However, due to the substantial weight loss observed in trial participants, the story didn’t end there. Researchers and healthcare providers began recommending the evaluation of tirzepatide as a primary weight loss medication. Data from subsequent studies stood up well, resulting in the FDA approving Zepound’s use as a weight management injection.

Mechanism of Action

Tirzepatide is a dual agonist. Agonists are chemical compounds that bind to specific receptors in the body, activating them to produce a biological response. They achieve this by mimicking the abilities of neurotransmitters or hormones. Tirzepatide binds with and activates the receptors for GLP-1 and GIP.

Both these hormones are released in the gut as a direct response to the presence of food. They play a key role in maintaining healthy blood sugar levels.

GLP-1 Receptor Activation

GLP-1 receptors are spread throughout the body. The pancreas contains them. So does the gastrointestinal tract. The central nervous system and cardiovascular systems contain GLP-1 receptors as well. By binding with the receptors in different organs, GLP-1 receptor agonists like tirzepatide produce different effects that ultimately lower blood glucose levels and reduce the desire to eat.

When the drug binds with the receptors in the pancreas, it causes the beta cells to release insulin, which reduces blood sugar. However, the response is glucose-dependent. It only occurs when blood sugar levels are high. This is not always the case with alternative medications, which can present a risk of hypoglycemia (low blood sugar).

In addition to stimulating the release of insulin, Tirzepatide suppresses the release of glucagon. Also produced by the pancreas, glucagon is a hormone that is normally released when blood sugar levels are low. It stimulates the liver, encouraging it to convert its stores of glycogen into glucose and release it into the blood to bring blood sugar levels back up.

Glucogen also pushes up blood sugar levels via a process known as gluconeogenesis that converts amino acids into glucose.

By asserting a measured level of control over both insulin and glucogen, tirzepatide helps keep blood sugar levels on an even keel. However, the benefits don’t end there.

Tirzepatide also binds with the GLP-1 receptors in the hypothalamus. This area of the brain has the task of controlling appetite and food intake. By acting on these receptors, the drug instructs the brain to stop sending out hunger signals.

Still acting in its role as a GLP-1 receptor agonist, tirzepatide slows down gastric emptying, causing food to remain in the stomach for longer. This has two main benefits.

Firstly, by causing food to empty from the stomach into the small intestine more slowly, the drug helps reduce the risk of post-meal blood sugar spikes. Secondly, the food’s prolonged presence in the stomach extends the feeling of satiety that normally follows meals, further adding to the appetite-suppressing effect.

GIP Receptor Activation

Although there was a time when GIP was only associated with insulin secretion in response to high blood sugar, we now know it serves other roles as well. 

Recent research reveals GIP receptors aren’t only located in the pancreas. They are present in adipose tissue, the gut, and the central nervous system as well.

When tirzepatide activates GIP receptors in the pancreas, it enhances insulin synthesis and release in a similar way to GLP-1. By providing analogs of both hormones instead of one, the drug presents a double-pronged approach to blood sugar control that gives it an edge over single-action analogs like semaglutide.

The activation of GIP receptors in adipose tissue is beneficial too because it appears to help module lipid metabolism. GIP may also play a role in energy utilization and storage.

However, tirzepatide’s influence on fat cells seems to be more subtle than that of the natural incretin. Some studies suggest it may help improve blood lipid profiles and aid fat loss but further research is necessary.

GIP receptor activation in the central nervous system may also have a positive influence on energy intake but, again, this is an area that requires further study.

 Clinical Trials and Efficacy

 The efficacy of tirzepatide in promoting weight loss has been evaluated through a series of rigorous clinical trials. Most notably under the SURMOUNT clinical program.

Part of the SURPASS program, the SURMOUNT clinical trials assessed the safety and effectiveness of tirzepatide in overweight and obese people, with or without type 2 diabetes. They compared the effects of tirzepatide to placebos and other weight loss medications across various populations and settings.

SURMOUNT-1

Data from SURMOUNT-1 provides compelling evidence of tirzepatide’s value as a weight loss aid. This global, multicenter, double-blind study consisted of non-diabetic participants who were overweight or obese.

The study participants were randomized to receive weekly injections of tirzepatide at various doses or a placebo.

The results were striking. At the highest dose, tirzepatide achieved an average weight reduction significantly greater than that of the placebo, with many participants experiencing a weight loss of over 15% of their initial body weight. This level of efficacy was greater than that of any of the weight loss medications available at the time.

SURMOUNT-2, SURMOUNT-3, and Beyond

Subsequent trials, including SURMOUNT-2 and SURMOUNT-3, sought to expand on these findings by including participants with type 2 diabetes and comparing tirzepatide to other antidiabetic agents with weight loss properties. Once again, tirzepatide demonstrated superior glycemic control and also outperformed competing drugs in terms of weight reduction.

Comparative Efficacy

Comparisons with other weight loss medications shed light on the quality of tirzepatide’s effects. In head-to-head trials, tirzepatide consistently induced more significant weight loss than other GLP-1 receptor agonists, such as semaglutide.

For example, participants receiving tirzepatide showed a greater reduction in body weight compared to those on semaglutide, with a more pronounced effect on waist circumference and cardiometabolic parameters.

Tirzepatide Side Effects and Risks

Like any other prescription medication, Tirzepatide can cause side effects. The range of side effects varies from common, mild reactions to rarer, more serious ones, some of which may be life-threatening.

Common Side Effects

The most frequently reported side effects of tirzepatide are gastrointestinal. Side effects of this type are typically mild to moderate. They often disappear as the body adapts to the medication over time.

Common tirzepatide side effects include:

  • Nausea: A significant number of patients experience nausea, especially during the initial stages of treatment.
  • Diarrhea: Loose stools or an increase in the frequency of bowel movements is a common problem.
  • Vomiting: Some users experience vomiting, which can contribute to fluid loss and dehydration.
  • Decreased Appetite: Many patients report a reduced desire to eat, which can be beneficial for weight loss.
  • Constipation: A decrease in bowel movements or difficulty having bowel movements is another common problem.
  • Abdominal Pain: Discomfort or pain in the stomach area is also reported by some patients.
  • Dyspepsia: Also known as indigestion, this can manifest as bloating, gas, or an upset stomach.

Rare but Serious Potential Adverse Reactions

Although less common, tirzepatide usage can also involve more serious health risks:

  • Pancreatitis (inflammation of the pancreas): The main symptom of pancreatitis is severe abdominal pain that may radiate to the back. There may also be nausea, vomiting, and fever. Without proper treatment, pancreatitis can be fatal.
  • Thyroid tumors: Early clinical trial data shows GLP-receptor agonists caused thyroid tumors in animals. Because of this, the FDA insists tirzepatide and similar drugs be distributed with appropriate warnings. Research published in Diabetes Care in November 2022 raises further concerns in this area. It suggests drugs of this type may increase the risk of all thyroid cancer and medullary thyroid cancer. In particular after 1–3 years of usage.
  • Hypoglycemia: Especially when used in combination with other diabetes medications, tirzepatide can cause low blood sugar levels. Typical symptoms may include dizziness, sweating, confusion, and even loss of consciousness.
  • Kidney problems: Tirzepatide may have the potential to make chronic kidney disease worse or cause kidney failure.
  • Severe Gastrointestinal Disease: Including severe gastric motility disorders, such as gastroparesis.
  • Severe Allergic Reactions: Symptoms of allergic reaction may include rash, itching, and swelling of the face, lips, tongue, or throat. There is also a risk of anaphylactic shock.

On the great scale of things, tirzepatide is still a new drug. As more people use it, additional side effects may come to light.

Anyone considering using tirzepatide or alternative GLP-1 receptor agonists needs to be aware the FDA is currently evaluating reports that suggest medications of this type are causing people to experience suicidal thoughts or actions.

Guidance on When to Seek Medical Attention

Tirzepatide users who experience severe side effects or signs of an allergic reaction will need to seek medical help immediately.

Things to look out for include:

  • Persistent or severe abdominal pain, which could indicate pancreatitis.
  • Symptoms of low blood sugar, such as shaking, sweating, rapid heartbeat, changes in vision, hunger, headache, or mood changes, especially if they do not improve after consuming a fast-acting carbohydrate.
  • Signs of kidney problems, such as a significant decrease in urine output, swelling in the feet or ankles, and fatigue.
  • Any signs of an allergic reaction, such as difficulty breathing, swelling of the face or throat, severe rash, or itching.

Tirzepatide users are also encouraged to report any side effects they experience to a qualified health care professional. Even if the side effects are not listed above.

Tirzepatide Dosage and Administration

The administration of tirzepatide for weight loss is a carefully calibrated process that is constantly supervised by a healthcare professional. The dosage can vary depending on individual factors such as the user’s response to the medication, their current health condition, and their weight loss goals.

Initial Dosage

Tirzepatide treatment typically begins with a low dose to help prevent or reduce the intensity of side effects. 

The initial dose is 2.5 mg per week. Presuming a good response and no adverse issues, the dose increases to 5 mg for weeks 5 through to 9. It then increases every four weeks until patients reach the maximum dose of 15 mg per week.

Some users may respond well to lower doses in which case, the prescription will remain at the appropriate maintenance dose.

Administration Guidance

Tirzepatide is administered just under the skin, never into a muscle or vein. The drug comes in a special disposable injector pen that automatically delivers the correct dose. 

Typical injection sites include the abdomen, upper thighs, and upper arms. It’s best to rotate the injection site. Doing so will help prevent bruising and skin irritation.

The healthcare professional who prescribes the medication will also provide guidance on the correct usage, storage, and disposal of the used injector pens.

Tirzepatide Vs. Alternative Weight Management Drugs

Tirzepatide is still a relatively new option for those seeking weight loss support. Although Mounjaro has been used off-label since 2022, Zepbound did not gain FDA approval for weight loss until the end of 2023. It’s still very much a new kid on the block but is already presenting stiff competition to other better-established options.

Tirzepatide vs. Other GLP-1 Receptor Agonists

Tirzepatide targets GLP-1 receptors and GIP receptors as well. None of the other weight loss shots can do this.  Data from clinical trials shows the drug’s dual action nature allows gives it greater value as a weight loss enhancer.

However, although all GLP-1 receptor agonists have a similar side effect profile, it’s possible that tirzepatide’s ability to mimic GIP may present additional risks as well as greater benefits.

As yet there are no signs that this is the case, but tirzepatide is still a relatively new drug. There is no way to be certain what issues may come to light in the future.

GLP-1 receptor agonist drugs are expensive. Tirzepatide is no exception. Zepbound has a list price of $1059 per month, with Mounjaro coming in roughly $30 cheaper.

Both options are cheaper than Semaglutide when it’s distributed as Wegovy because it has a list price of $1349 per month. Ozempic (semaglutide for type 2 diabetes) generally costs $850 to $1000 per month.

However, liraglutide which has FDA approval for treating type 2 diabetes, under the Victoza brand name, and is often used off-label for weight loss, is in a similar price bracket as Wegovy. Bearing in mind its greater potential, tirzepatide, though expensive, would appear to be very competitively priced.

Tirzepatide vs. Phentermine

Phentermine is an appetite-suppressing diet pill that’s been available via prescription since 1959. It’s still very popular.

It’s possible to buy a 30-day supply of the generic drug for less than $20. With a cost of $76.12 to $126 per month, Adipex-P costs significantly more but is still much cheaper to use than tirzepatide.

However, Tirzepatide is suitable for long-term use. Phentermine is not. It’s a form of amphetamine that poses a threat of addiction. Because of this, only available as a short-term weight-management treatment. The FDA only permits doctors to prescribe it for a maximum of 12 weeks. Few phentermine patients receive it that long.

Phentermine can cause high blood pressure and increase the risk of cardiovascular events such as heart attacks and strokes. Tirzepatide is not known to present these risks but it could be argued that some of its potential side effects are as bad or worse.

Tirzepatide vs. Orlistat

Orlistat works differently from both tirzepatide and phentermine. It’s a fat-blocking diet pill that works as a lipase inhibitor. Lipase is the digestive enzyme responsible for breaking down dietary fats. 

Orlistat is available under two different brand names. Xenical is only available with a prescription. Allie is available to buy over-the-counter (OTC) but it isn’t as strong.

Xenical blocks around 30% of all fat its users consume. Alli is a half-strength version that blocks considerably less. 

Fat is an energy-dense food that provides 9 calories per gram, so Orlistat can be effective for lowering daily calorie intake. However, tirzepatide is a more powerful option and, in this case, the difference in price is not so notable because a 30-day supply of Xenical costs around $800.

As far as the potential adverse issues go, Orlistat comes out on top. It can cause stomach upsets but is not associated with any major health threats. It also causes greasy stools and may cause embarrassment to users who eat too much fat and stray too far from the nearest toilet.

Additionally, Orlistat usage may cause people to become deficient in the fat-soluble vitamins A, D, E, and K.

Tirzepatide Eligibility Considerations

Many people who are keen to use tirzepatide for weight loss may not be able to obtain it. Several factors can have a bearing on eligibility and the issue of a prescription.

BMI Restrictions

The FDA restricts the availability of approved weight loss drugs. To be eligible to use them, patients need to have a body mass index (BMI) that’s high enough to make them be classified as overweight or obese.

People who have a BMI of 30+ (obese) may be good candidates for a Zepbound prescription. Some people with a BMI of 27+ (overweight) may be eligible too but only if they also have a weight-related medical condition such as obstructive sleep apnea (OSA) or cardiovascular disease. 

Although doctors have to stick to these rules for approved weight loss medications, there are no rules in place regarding off-label treatments. So, although doctors may not be able to prescribe tirzepatide as Zepbound, they may be willing to prescribe it as Mounjaro instead.

However, several other factors can influence eligibility as well.

Medical Conditions Influencing Prescription

Certain medical conditions may influence the decision to prescribe tirzepatide:

  • Type 2 Diabetes: Tirzepatide may be particularly beneficial for users with type 2 diabetes. However, using it alongside other anti-diabetic medicines may increase the risk of hypoglycemia. Where such medications are in use and changing them is not feasible, it may not be possible to use tirzepatide.
  • Pancreatic Disease: A history of pancreatitis may require careful consideration due to the potential risk of tirzepatide-associated pancreatitis.
  • Gastrointestinal Disorders: Patients with severe gastrointestinal disorders, such as gastroparesis, may not be suitable candidates for tirzepatide due to its gastrointestinal motility effects.
  • Thyroid Carcinoma: As with other GLP-1 receptor agonists, tirzepatide carries a warning regarding thyroid C-cell tumors, making it unsuitable for people with a personal or family history of medullary thyroid carcinoma or people with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
  • Renal Impairment: The drug’s safety and efficacy may be reduced in people with renal impairment.dss

Use of Certain Medications

The use of other medications can also influence the decision to prescribe tirzepatide. Interactions with other drugs may alter the effectiveness of tirzepatide or increase the risk of adverse events.

For example, because it slows down gastric emptying, tirzepatide may interfere with the absorption of oral medications.

Insurance and Cost Considerations for Tirzepatide

Tirzepatide is not cheap. Many people who want to use it may not be able to afford it and may lack appropriate insurance coverage.

Insurance Coverage

  • Prescription Plans: Many insurance plans have specific criteria for weight loss medication coverage. They may require documents that prove there is an inability to lose weight through conventional methods such as diet and exercise, or the presence of obesity-related comorbidities.
  • Prior Authorization: Tirzepatide coverage may require prior authorization from the insurance provider. This process involves submitting a request that outlines the medical necessity based on the patient’s health status, medical history, and failure to lose weight with a reduced-calorie diet and increased levels of physical activity.
  • Tiered Formulary: If tirzepatide is included in the insurance provider’s formulary, it may fall under a higher tier, which often means higher copays. It’s essential to check the specifics of the insurance plan’s medication tiers.
  • Exclusions: Some insurance plans may exclude weight loss medications from coverage altogether. Alternatively, they may have specific exclusions for newer medications like tirzepatide.

Medicare and Medicaid

  • Medicare: Standard Medicare Part D prescription drug plans typically do not cover medications for weight loss. However, some Medicare Advantage plans or Part D plans may offer additional benefits that could include weight loss medications under certain conditions.
  • Medicaid: Coverage for weight loss medications varies significantly by state, and patients should check with their state’s Medicaid program to understand the eligibility criteria for tirzepatide coverage.

Out-of-Pocket Costs

  • Without Insurance: For patients without insurance coverage or for those whose insurance does not cover tirzepatide, the out-of-pocket cost can be substantial. The exact cost can vary based on location and pharmacy,
  • Copay Cards and Assistance Programs: The manufacturer of tirzepatide may offer copay cards or patient assistance programs to help reduce the out-of-pocket costs for eligible patients. These programs are typically intended for patients with private insurance and are not usually available to patients on Medicare, Medicaid, or other federally funded programs.
  • Long-Term Commitment: Since weight management is a long-term commitment, the cumulative cost of tirzepatide usage over time can strongly influence the decision to initiate or continue treatment.

Patient Experiences and Testimonials with Tirzepatide

Many users report positive experiences using Tirzepatide for weight loss. Some of them also remark that it’s easy to use.

However, there are also reports of side effects such as diarrhea, itchy and red blotches at the injection site, constipation, sour stomach, and occasional heartburn.

The Potential for Future Innovations

There is currently speculation about whether tirzepatide may become available in an oral form in the future. Although the manufacturer does not appear to have any plans to do so, it’s still not beyond the realms of possibility.

Shortly after semaglutide gained FDA approval as an injectible medication, the manufacturer developed a semaglutide pill. Although, tirzepatide is a more complex drug it may be possible to move in a similar direction.

Challenges in Developing Oral Peptide Medications

Peptide-based drugs like tirzepatide are typically hard to absorb in oral form due to degradation by gastrointestinal enzymes and poor permeability across the intestinal epithelium. Ensuring stability in the harsh acidic environment of the stomach presents a major hurdle for oral peptide drug development.

Bioavailability may also be an issue. Creating tirzepatide pill that can match the therapeutic abilities of the weekly shots might not be easy. 

Advancements in Drug Delivery Technology

Although there may be challenges, there are also potential solutions. Advances in encapsulation technology may make it possible to protect the drug with a protective coating that may help it safely through the stomach. Probiotic supplement manufacturers often do something similar.

It may also be possible to use permeation enhancers to ease the transport of the drug through the intestinal walls and into the blood. Alternatively, it may be feasible to utilize advanced carrier systems or nanoparticles to transport the active drug and improve its stability and absorption.

Given the success of oral semaglutide, there is a clear industry interest in developing oral formulations for peptide-based therapies.  A pill version of tirzepatide may be very appealing to many patients, potentially improving compliance and quality of life for those requiring long-term treatment.

Furthermore, the potential market for an oral version of tirzepatide is substantial. This provides a strong financial incentive to develop one.

So, although there are significant scientific and technical challenges to overcome, the development of tirzepatide diet pills is certainly plausible and would align with current trends in diabetes and obesity treatment.

If such an advancement is achieved, it could have a profound impact on the therapeutic landscape and patient experience.

Conclusion

Tirzepatide is one of the most exciting and innovative drugs of our time. Although it was originally developed to help type 2 diabetics control their blood sugar levels, as with many similar drugs, it shows great promise as an aid for those seeking body weight reduction.

Tirzepatide combines the actions of GLP-1 and GIP to enhance insulin secretion, suppress appetite, and reduce food intake. This dual agonist action makes it unique and allows it to outperform alternative options such as semaglutide.

Despite its advantages, tirzepatide is not without its limitations. Some patients experience side effects, which, although typically manageable and temporary, can affect quality of life and treatment adherence.

The cost of tirzepatide can also be a barrier. It’s a very expensive option to use and may not be covered by insurance.

However, the dosing schedule certainly works in the drug’s favor. People who use it only require one injection per week. This can be very appealing.

Nevertheless, there are still plenty of people who prefer to take pills than to use needles, even if it is only one injection per week. Looking forward, the potential development of an oral form of tirzepatide is an exciting prospect.

Such an innovation would not only expand the drug’s accessibility but also cater to patient preferences, potentially improving adherence and satisfaction.

References and Further Reading

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About the author

Peter Williams has over 20 years of experience as an endocrinologist. Peter specializes in the study of diabetes, thyroid and parathyroid disorders, obesity, lipids disorders, and hormonal imbalances. He is actively involved in research investigating new medications and technologies for managing these chronic conditions.