Episode 64: GLP-1s Without the Side Effects? This Might Be the Answer

Podcast Summary

Overview

In this episode of the Pound of Cure Weight Loss Podcast, Dr. Matthew Weiner and Zoë discuss two major topics shaping the weight loss medication landscape in 2024: the end of compounded GLP-1 medications and the promising strategy of microdosing these medications. The conversation provides practical guidance for patients navigating these changes while emphasizing personalized care and innovative dosing strategies.

The End of Compounded GLP-1 Medications

Final Deadlines Are Here

More from this episode

Dr. Weiner confirms that compounded GLP-1 medications are officially coming to an end. Small compounding pharmacies (503A facilities) had to stop production by April 22nd, while larger compounding pharmacies must cease by May 22nd. This episode was recorded on April 25th, meaning the small pharmacies have already stopped.

The reason for this shutdown is straightforward: patent law. Eli Lilly holds the patent for tirzepatide (Mounjaro, Zepbound), and Novo Nordisk holds the patent for semaglutide (Ozempic, Wegovy). Compounding pharmacies were only allowed to produce these medications because they were on the FDA shortage list. Now that the shortage has been resolved, the legal basis for compounding has ended.

Safety Concerns With Remaining Products

Dr. Weiner emphasizes a critical point: any legitimate, risk-aware healthcare provider or business has already exited the compounded medication market. The products still available come from overseas manufacturing plants with unknown quality controls. These are not coming from Eli Lilly or Novo Nordisk.

Two groups will likely continue selling these products despite the legal risks:

1. Gray market or black market operators willing to take significant business and legal risks
2. Large venture-capital-backed companies like Hims, Hers, and Ro that have protected their assets and can fold quickly if legal action comes

Dr. Weiner states clearly that if someone offered him free compounded medications to sell and make money, he would refuse. The risk to patient safety and his practice simply is not worth it. He describes himself as risk-averse, noting he has been to Las Vegas five or six times and never gambled a single dollar.

What This Means For Patients

Patients need to understand where their medications are coming from. If providers are willing to take legal and business risks by continuing to sell compounded products, they are also willing to take risks with patient health and safety. Zoë reinforces that legitimate providers have moved away from these products.

Creative Sourcing Strategies

International Options

The Pound of Cure practice has developed sourcing strategies using legitimate pharmaceutical products from other countries. They now source medications from Canada and Israel, where different formulations and dispensing methods are available that are not offered in the United States.

These international products are manufactured by the actual pharmaceutical companies (Eli Lilly and Novo Nordisk) but designed for different markets. They eliminate the safety concerns associated with compounded medications while still offering cost savings compared to U.S. retail prices.

U.S. Product Creative Dosing

The practice also uses creative dosing strategies with U.S. products. While this requires some medical expertise, Dr. Weiner notes that patients have become remarkably creative with these approaches. He credits his patients with teaching him many of these strategies.

Microdosing GLP-1 Medications: The Research

The 2018 Lancet Study

Dr. Weiner discusses a landmark study published in the prestigious medical journal Lancet in 2018. This research has been available for years, but Dr. Weiner admits he is somewhat embarrassed it took him time to fully appreciate its implications.

The study was a high-quality, double-blinded, placebo-controlled trial involving just under 1,000 participants. Researchers tested very low doses of semaglutide and compared results to placebo.

The Doses Tested

For context, Ozempic normally starts at 0.25 milligrams, with the next dose at 0.5 milligrams and the highest dose at 2.4 milligrams. The study looked at much smaller amounts:

• 0.05 milligrams (what Dr. Weiner calls "a whiff")
• 0.1 milligrams
• 0.2 milligrams
• 0.3 milligrams
• 0.4 milligrams

Impressive Results At Low Doses

The placebo group lost 2.3% of their body weight, which tells Dr. Weiner that participants received some dietary counseling and were actively trying to lose weight, not just taking a pill.

The results at low doses were remarkable:

• At 0.05 milligrams: 6% total body weight loss
• At 0.1 milligrams: 8.6% total body weight loss
• At 0.2, 0.3, and 0.4 milligrams: 11% to 14% total body weight loss

While these numbers do not quite match the 16% seen in the Wegovy trial at 2.4 milligrams, they demonstrate that the majority of weight loss occurs at the lowest doses.

Why Microdosing Works

Reduced Side Effects

One of the most significant advantages of lower doses is reduced side effects. Zoë reports that many patients tell her they feel great on lower doses. They are not thinking about food as much, they are less hungry, but they are not experiencing the nausea and other uncomfortable side effects that can occur at higher doses.

Not everyone experiences negative side effects at higher doses, but Zoë notes that the majority of people who can stay at lower doses avoid these problems entirely.

Better Nutrition Implementation

Zoë emphasizes that most patients who have struggled with weight loss for years are not lacking effort. They need that extra support to make their efforts effective. Microdosing provides just enough medication to quiet food noise, reduce hunger slightly, and decrease food volume.

With these modest changes, patients can successfully implement nutritional and lifestyle modifications. When they finally see the scale move after years of doing everything right without results, it provides powerful positive reinforcement and motivation.

The Motivation Factor

Dr. Weiner and Zoë both stress that success is the biggest motivator. When patients are trying hard but not seeing results, they eventually lose motivation and return to old habits. Even a tiny amount of medication can make all the difference in allowing nutritional changes to be effective.

Patient-Centered Care And Individualization

One Size Does Not Fit All

Dr. Weiner shares that after working with thousands of patients on these medications, he has found that everyone's story is different. There is a group of "super responders" who do extremely well with minimal intervention. These patients can take the medication, follow basic guidance, and achieve excellent results.

However, most patients require more individualized care. Their nutrition, dosing, side effect management, and overall journey are much more complicated and require extra assistance.

Real-World Example

Dr. Weiner describes a patient he spoke with recently who took 2.5 milligrams of tirzepatide (the lowest standard dose) and felt miserable. Using creative dosing strategies, they brought the dose down to 1 milligram, and the patient did much better. Some people simply respond well to much lower doses, and the flexibility to provide that is essential.

Additional Benefits Of Microdosing

Alcohol Reduction

Zoë mentions that many patients experience a decreased desire to drink alcohol on GLP-1 medications. Since alcohol is a significant source of empty calories, this can be a game-changer for people who are doing everything right with nutrition and exercise but still drinking regularly. Even a couple of drinks per night or a few times per week can prevent weight loss. If a microdose reduces that desire, it provides another pathway to success.

Long-Term Safety Considerations

Dr. Weiner addresses concerns about what might happen 20 or 30 years down the line with these medications. He explains the concept of "area under the curve," borrowed from calculus, which considers both dose and duration of medication use.

He compares this to smoking, which is measured in "pack years." Smoking one cigarette per day versus a full pack per day has vastly different impacts on cancer and heart disease risk. Similarly, taking a low dose of medication for many years has a much smaller cumulative exposure than taking a high dose.

If any long-term side effects emerge (and none have been identified yet), patients on lower doses will have hedged their bets and reduced their risk.

Patient Perspective On Risk

Zoë shares that several patients have told her the medication has been so life-changing that they do not care if there might be negative effects 20 years from now. They are getting their lives back today and living in a way that makes them happy. While not everyone shares this sentiment, it reflects the significant quality of life improvements many patients experience.

Cost Savings

Microdosing addresses cost in a major way. Using creative dosing strategies with overseas products, patients can access medications at lower prices while using less medication overall. The U.S. market is limited because you cannot get doses smaller than 0.25 milligrams of Ozempic or Wegovy, and the lowest dose of Zepbound is 2.5 milligrams. International products offer much more flexibility.

The Problem With U.S. Dosing Pens

Inferior Design

Dr. Weiner is direct in his assessment: the U.S. dosing pens for Wegovy and Zepbound are wrong. The FlexPen design available in Canada, Israel, and most other countries is far superior for patient use.

The international pens allow for in-between doses and lower starting points, which helps patients reduce side effects and enhance comfort. Since comfort equals long-term weight loss with these medications, this is not a minor issue.

Why Comfort Matters

Patients will not continue injecting something that makes them feel terrible. The goal is to feel better about your body, not worse. When providers have access to more flexible dosing options, patients have more opportunities to be comfortable and therefore sustain medication use over time.

The Profit Problem

Dr. Weiner believes Novo Nordisk and Eli Lilly are focused on profits rather than patient comfort. He hopes they will eventually recognize that offering more flexible dosing in the U.S. market will serve their long-term interests. Their patents last until 2032 for semaglutide and the late 2030s for tirzepatide. With competition coming, making medications more comfortable for patients will be crucial for maintaining market share.

Impact On Surgery Decisions

Dr. Weiner notes he is seeing more people consider bariatric surgery because they did not have the experience with medications they hoped for. Some of this is due to limited dosing options, and much of it is financial. If the pharmaceutical companies do not address these issues, it may cost them in sales.

The Pound of Cure Approach

Combining Modalities

As Dr. Weiner does more work combining medications with bariatric surgery, he is identifying many nuanced components of comprehensive weight loss care. The approach solidifies the pyramid model:

1. Foundation: Lifestyle and nutrition
2. Middle tier: Medications
3. Top tier: Bariatric surgery

Each level works far better when combined with the others, particularly the foundation of nutrition.

Platinum Program

The practice's Platinum Program focuses on creative dosing and sourcing strategies. Zoë and Dr. Weiner emphasize that their goal is patient-driven care, doing what is best for each individual patient to help them get the best results while keeping medications affordable.

Upcoming App Launch

Dr. Weiner is excited to announce that the Pound of Cure app will begin beta testing on May 9th. Patients enrolled in the nutrition program will automatically be offered a beta testing spot and will receive an email with login instructions using the same email address they use for the nutrition program.

The app has been designed to put everything patients need in one place, addressing a frequent patient request. While Dr. Weiner cannot promise it will work perfectly during beta testing, it is already functioning well, and the team will continue smoothing out any issues.

Key Takeaways For Patients

On Compounded Medications

Avoid any remaining compounded GLP-1 products. Legitimate providers have exited this market, and continuing to purchase these products carries significant safety risks. The providers still selling them are willing to take legal risks and are therefore willing to take risks with your health.

On Microdosing Strategy

Microdosing is supported by solid research from 2018 showing significant weight loss at very low doses. The benefits include:

• Fewer side effects
• Better ability to implement nutritional changes
• Increased motivation from seeing results
• Lower long-term safety risks
• Reduced cost
• Sustainable long-term use

On Dosing Flexibility

The U.S. dosing pens limit patient options and comfort. International products offer superior flexibility. If you are struggling with standard U.S. doses, creative dosing strategies or international sourcing through legitimate medical channels may help.

On Individualized Care

Every patient's journey is different. What works for a super responder may not work for you. Working with providers who understand nuanced dosing, nutrition integration, and side effect management makes a significant difference in outcomes.

On Nutrition Integration

Medications work best when combined with solid nutritional guidance. The medication provides the support needed to make lifestyle changes effective, but the lifestyle changes remain the foundation of lasting weight loss.

Looking Forward

Dr. Weiner and Zoë note that the landscape of weight loss medications continues to evolve rapidly. New drugs are coming in the next year or so, though they have not tackled those in detail yet. The practice is committed to staying current with research and providing patients with evidence-based, personalized care.

The episode represents an important moment in the transition from the compounding era to a new phase of GLP-1 medication use, focused on patient safety, creative legitimate sourcing, and optimized dosing strategies based on solid research.

Weight loss topics covered in this episode

This conversation is part of the Pound of Cure approach to evidence-based weight loss education, including bariatric surgery, GLP-1 medications, nutrition counseling, metabolic health, and long-term patient support.

For more context, explore our guides to GLP-1 medications, bariatric surgery in Tucson, and the Metabolic Reset Diet.