Compounded Tirzepatide for Diabetes and Weight Loss: Dosage, Safety, Legality

Introduction to Tirzepatide and Compounding Pharmacies

Tirzepatide is a new medication that was approved by the FDA in 2022 for treating type 2 diabetes. It belongs to a class of drugs called GLP-1 receptor agonists, which work by mimicking the effects of a hormone called glucagon-like peptide-1 (GLP-1). This hormone helps regulate blood sugar levels by stimulating the release of insulin when blood sugar is high, suppressing the release of glucose from the liver, and slowing down digestion to decrease the absorption of sugar into the bloodstream.

In clinical trials, tirzepatide has been shown to be very effective at lowering A1C levels (a measure of blood sugar control over the past 2-3 months) and promoting weight loss in people with type 2 diabetes. Compared to other GLP-1 drugs like semaglutide (Ozempic), tirzepatide appears to have greater efficacy for improving glycemic control and supporting weight loss at comparable doses.

However, like other new brand name drugs, tirzepatide can be very expensive. The list price for a month's supply of the highest dose is around $1000. For people with high deductible health plans or no insurance coverage, such high costs for tirzepatide can make the medication unaffordable.

This has led some people to seek out compounded versions of tirzepatide from specialty pharmacies. Compounding pharmacies can create customized medications by combining, mixing, or altering ingredients. For tirzepatide, the pharmacies will compound a version of the drug at a lower dose or different formulation for a cheaper price.

Benefits of Compounded Tirzepatide

There are some potential advantages to using compounded tirzepatide:

• Lower cost - Compounded tirzepatide can be substantially cheaper than the branded version.
• Accessibility - Compounding provides access to the medication for those who cannot afford or obtain insurance coverage for the branded drug.
• Customization - Compounding allows for individualization of the dose or formulation which may better meet a person's needs.
• Alternate routes - Compounded tirzepatide can be made into topical creams, oral dissolving tablets, or other alternate delivery methods.

Risks and Concerns with Compounded Medications

However, there are also some important risks and concerns to consider with using compounded medications like tirzepatide:

• Quality - Compounding facilities are not held to the same FDA approval standards as pharmaceutical companies, so there may be more variability or impurities.
• Efficacy - Lower doses or altered formulations of compounded tirzepatide may not achieve the same results as the branded medication.
• Side effects - Differences in compounding could potentially change the side effect profile. Long-term safety is unknown.
• Legality - Getting compounded tirzepatide for weight loss only, instead of an FDA-approved indication like diabetes, may be considered off-label use.

How Tirzepatide Works to Lower Blood Sugar and Promote Weight Loss

To understand the potential risks and benefits of compounded tirzepatide, it helps to first understand how this medication works in the body:

Incretin Effect

Tirzepatide is a GLP-1 receptor agonist. This means it mimics the effects of GLP-1, an incretin hormone produced in the intestines in response to food intake. Incretins like GLP-1 potentiate the release of insulin from pancreatic beta cells when blood glucose is elevated after eating.

In people with type 2 diabetes, the incretin effect is diminished, contributing to insufficient insulin secretion and high post-meal blood sugar levels. GLP-1 medicines like tirzepatide help restore the incretin response.

Slowing Gastric Emptying

GLP-1 receptor activation also slows down gastric emptying, which is the rate at which food empties from the stomach into the small intestine. By slowing gastric motility, tirzepatide prolongs feelings of fullness and delays the digestion and absorption of glucose following meals.

This blunting of post-meal glucose spikes helps lower HbA1c levels in people with diabetes. Slower gastric emptying may also contribute to weight loss by reducing appetite and calorie intake.

Effects on Appetite and Satiety

Tirzepatide is thought to act on regions of the brain involved in appetite regulation, such as the hypothalamus. By modulating signals of hunger, fullness and satiety, tirzepatide helps suppress appetite and enhance feelings of fullness after eating.

Through these central nervous system effects, tirzepatide can lead to reduced food intake and weight loss. The combination of delayed gastric emptying and appetite modulation promotes weight loss beyond what would be expected from improved blood sugar control alone.

Clinical Trial Results for Tirzepatide

In phase 3 clinical trials, tirzepatide has demonstrated very promising results for improving markers of glycemic control and inducing weight loss in people with type 2 diabetes:

Glycemic Control

• Doses of 5mg, 10mg and 15mg tirzepatide all significantly reduced A1c from baseline after 26 weeks compared to placebo, with higher doses producing greater reductions up to 2.37%.
• Up to 79% of those on tirzepatide reached an A1c below 7% compared to 13% of the placebo group.
• Tirzepatide also lowered fasting blood glucose levels significantly more than placebo.

Weight Loss

• Average weight loss with tirzepatide ranged from 7.9 kg (5mg) up to 12.4 kg (15mg) over 26 weeks.
• 35-41% of those on tirzepatide lost at least 10% body weight versus 5% on placebo.
• Improvements were seen in waist circumference, body fat percentage, and BMI.

The efficacy results from these clinical trials demonstrate that tirzepatide can have substantial benefits for improving glycemic control and inducing weight loss in patients with type 2 diabetes at the studied doses of 5-15mg.

Safety and Side Effects

In the clinical trials, the most common side effects with tirzepatide were gastrointestinal in nature, including:

• Nausea - Occurred in up to 28% on highest dose
• Diarrhea - Occurred in up to 16% on highest dose
• Vomiting - Occurred in up to 10% on highest dose
• Decreased appetite
• Constipation
• Dyspepsia
• Abdominal pain

These GI side effects were generally mild to moderate and tended to improve over time. The risk of side effects was dose-dependent.

Other potential side effects include headaches, fatigue, sinus congestion, upper respiratory tract infections, and reactions at the injection site.

In the clinical trials, serious side effects with tirzepatide were rare. There was no increased risk of diabetic retinopathy complications or medullary thyroid carcinoma compared to placebo.

Hypoglycemia occurred more frequently with tirzepatide in patients also taking insulin or insulin secretagogues due to the increased glucose lowering efficacy. Medication adjustments helped reduce hypoglycemia risk.

FDA Approved Dosing for Tirzepatide

Tirzepatide was approved by the FDA in May 2022 for glycemic control in adults with type 2 diabetes. The approved dosing regimen begins with a low dose that is then escalated over time to improve tolerability to side effects.

The FDA approved dosing schedule for tirzepatide is as follows:

• Starting dose is 2.5mg injected subcutaneously once weekly
• After 4 weeks, increase to 5mg once weekly
• After at least 4 weeks at 5mg, increase to 10mg once weekly
• After at least 4 weeks at 10mg, increase to 15mg once weekly (maximum dose)

This gradual increase in dosing helps minimize GI side effects. If tolerated, the 15mg once weekly dose provides the greatest efficacy for A1c and weight reduction based on the clinical trials.

Tirzepatide should be taken consistently with 1 full day between doses. It can be injected any time of day with or without meals.

Other Key Administration Tips

• Rotate injection sites between abdomen, thighs, or upper arms
• Inject subcutaneously into an area with at least 1 inch of space around it
• Use pen needle between 4-12mm; shorter needles for lean patients
• Store unopened pens in the refrigerator until first use
• Once in use, can be kept at room temperature for up to 4 weeks
• Discard if solution is discolored or contains particles

Compounded Tirzepatide Formulations and Dosing

Because tirzepatide is such a new medication, compounded formulations are not as standardized as for other established diabetes drugs. However, some common approaches to compounding tirzepatide include:

Lower Doses

Some compounding pharmacies offer tirzepatide doses lower than 2.5mg, such as 1mg or 1.25mg per week. The thought is a reduced dose may provide cost savings and still yield efficacy, especially when transitioning from other GLP-1 agonists.

However, there is no clinical evidence establishing the safety or efficacy of such low doses. It is unclear if glycemic and weight benefits would be comparable to FDA approved dosing.

Weight Loss Formulations

Other compounding formulas use higher, weight loss oriented doses of tirzepatide from 5-15mg per week. Often, these preparations are promoted for weight loss only, instead of treating diabetes.

Using compounded tirzepatide purely for weight reduction could be considered off-label use. The long-term safety of higher doses without diabetes monitoring is unknown.

Creams/Troches

Some compounding pharmacies offer topical tirzepatide creams or oral troches (lozenges). These aim to provide transmucosal absorption of the medication to avoid injections.

However, the absorption and efficacy of these alternative delivery methods have not been clinically evaluated. It is questionable how well they mimic FDA-approved injected tirzepatide.

Advantages and Disadvantages of Compounded Tirzepatide

Given the variety of compounded tirzepatide options available, what are some potential pros and cons of pursuing this over the FDA-approved branded medication?

Potential Advantages

• Cost Savings - Compounded tirzepatide can be thousands of dollars cheaper per year than branded.
• Insurance Coverage - Some compounding pharmacies assist with insurance claims for compounded medications.
• Customization - Compounding allows personalized doses or formulations.

Potential Disadvantages

• Efficacy - Lower doses or alternative delivery methods may be less effective than injections.
• Safety - Purity, sterility, and long-term safety are bigger concerns with compounds.
• Off-Label Use - Compounded tirzepatide prescribed for weight loss only is off-label.
• Monitoring - Those using compounded tirzepatide may not undergo the same medical monitoring as patients using it for diabetes under a doctor.

Is Compounded Tirzepatide Legal?

The legality of compounded tirzepatide depends on the specific circumstances:

• Compounding tirzepatide for diabetes treatment at lower doses is likely permissible, though not proven effective or safe.
• Compounding tirzepatide purely for weight loss may be considered off-label use without an FDA-approved indication.
• Topical creams, troches, sprays and other alternative delivery methods are all considered off-label use.

While personal compounding by a pharmacy for an individual patient may be allowed, it is illegal for compounding pharmacies to manufacture and sell unapproved drugs en masse without prescriptions prior to receiving orders. The FDA provides oversight of compounding facilities to enforce regulations.

Doctors who directly partner with compounding pharmacies to prescribe compounded medications in bulk for financial gain may also be considered in violation of off-label marketing rules.

Is Compounded Tirzepatide Safe?

The safety profile of compounded tirzepatide is less certain than the branded medication reviewed by the FDA. There are some risks to keep in mind with compounds:

• Purity - Compounding labs may not use active pharmaceutical ingredients from verified sources.
• Sterility - Contamination and improper hygiene have led to infections from contaminated compounds in the past.
• Quality - Compounding facilities have more variability in accuracy of dosing.
• Side effects - Alterations like higher doses or delivery changes may impact side effect profile.
• Drug interactions - Compounded medications often lack pharmacokinetic studies evaluating potential drug interactions.

These risks may be minimized by using an experienced, high-quality compounding pharmacy that follows best practices. However, quality can still be inconsistent across different pharmacies. Vigilance for side effects and medical supervision is recommended when using compounded tirzepatide, especially without an FDA-approved indication.

Is Compounded Tirzepatide Effective for Weight Loss?

Unfortunately, there are currently no published studies examining the efficacy of compounded tirzepatide formulations for weight loss. Several factors make effectiveness for weight reduction unclear:

• Lower doses may reduce weight loss effects compared to clinical trial doses of 5mg to 15mg weekly.
• Alternative delivery methods like topical creams have unproven absorption and bioavailability.
• Most use is off-label without medical monitoring and diet and exercise programs tailored for weight loss.
• The placebo effect may inflate some perceived benefits in the absence of head-to-head clinical studies.

Anecdotal reports of weight loss with compounded tirzepatide exist. However, robust clinical data is lacking. FDA-approved tirzepatide dosed appropriately provides the most evidence-based option for weight reduction at this time.

Talking to Your Doctor About Compounded Tirzepatide

If you are interested in using compounded tirzepatide for diabetes or weight loss management, speaking with your physician is recommended. They can help assess if this an appropriate option for you based on your medical history and priorities for treatment.

Some questions to discuss with your doctor include:

• Would branded tirzepatide be a good medication choice for me if cost was not an issue?
• Am I an appropriate candidate for off-label use of compounded tirzepatide purely for weight loss?
• Can you work with a compounding pharmacy to prescribe an evidence-based dose and formulation?
• Will you monitor my health, weight, and labs if I use compounded tirzepatide?
• What side effects or drug interactions should I watch out for?

Having an open conversation with your physician can help decide if compounded t

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult with a healthcare professional before starting any new treatment regimen.