Tag: GLP-1 Agonists

Compounded Semaglutide and Tirzepatide: What to Know Now

On By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

When patients ask me about compounded weight loss drugs like semaglutide and tirzepatide, I take a deep breath. The topic is complicated and keeps changing. I won’t just tell patients to avoid them. They’re already looking for these options, and my job is to help them navigate the risks safely.

Dr. Beverly Tchang’s “swim safely” analogy fits well. We can’t stop people from diving into the ocean of compounded products, but we can at least give them floaties: information, caution, and tools to make better decisions. (Tchang, Medscape)

Here’s how I explain it to patients and colleagues, updated with the most recent data.

Why compounded versions exist

When semaglutide and tirzepatide injections were in short supply a few years ago, patients turned to compounding pharmacies that offered custom formulations, often at a lower price. (GoodRx)

In late 2024, the FDA ended the declared shortage of tirzepatide. (Stat News) By early 2025, semaglutide (Ozempic and Wegovy) followed. Once the shortages ended, enforcement ramped up against compounded versions. (GoodRx)

Now, compounded versions are only legal in narrow circumstances, such as when a patient has a medical need that can’t be met by an approved product. (GoodRx)

In December 2024, the FDA sent warning letters to several companies selling unapproved GLP-1 drugs labeled “for research use only.” (Reuters) Some of these contained no active ingredient, incorrect salt forms, or inconsistent potency. (Verywell Health)

Key risks and what to look for

Not all compounding pharmacies operate at the same standard. A friendly local pharmacist doesn’t necessarily mean the product is safe. Dr. Tchang’s checklist gives a good framework for evaluating any compounded GLP-1 medication. A simplified version: look for a pharmacy where the medication is prescribed by a licensed provider, there are no disciplinary actions on file, the pharmacy has been in business for more than a year, only semaglutide base is used (not a salt form), and the facility is FDA-registered or FDA-inspected; it should also be able to ship sterile drugs safely to all 50 states.

If a compounding pharmacy cannot meet these criteria, that’s a red flag. Ask directly for documentation. If they can’t provide it, walk away.

Some compounders also mix in vitamins or preservatives to make their product “different” from the brand name; that may sound harmless, but combining untested additives with peptides can change how the drug behaves. (GoodRx)

A few are promoting oral or sublingual forms of semaglutide and tirzepatide. These seem attractive for patients who don’t like injections, but they haven’t been validated in clinical trials, and absorption is unpredictable. (Omada Health)

Even small changes in formulation or dosing can interrupt treatment and cause rebound weight gain or side effects.

How I approach this with patients

When a patient says, “I found a compounding pharmacy that sells it for half the price,” I acknowledge their concern. Access and cost are real issues. But I explain that the regulatory situation has changed. If an FDA-approved version is available, that’s the standard we should use first.

I encourage patients to ask the pharmacy for their certificate of analysis, sterility test results, and ingredient source; if the pharmacy hesitates or says it’s proprietary, that’s enough reason to stop.

One patient of mine was on a compounded semaglutide microdose that wasn’t commercially available, at least as she described it to me. I never could pin down what she was actually getting. The compounder wouldn’t release potency data either. We moved her to a low-dose commercial version instead. Weight loss slowed a little. Safety and consistency improved, and I knew what was in the pen.

We also reviewed manufacturer assistance programs and insurance coverage. Many patients don’t realize that drug makers often cap out-of-pocket costs for brand medications; cost confusion is one of the biggest drivers behind compounded use.

The FDA’s BeSafeRx campaign

The FDA has an ongoing public safety campaign called BeSafeRx, designed to help patients and providers verify the legitimacy of online pharmacies and compounded drug sources; it offers tools to check pharmacy licenses, identify red flags, and report suspicious products.

It’s a good resource for anyone considering buying compounded or online medications; I often share it directly with patients so they can see what trustworthy sourcing looks like.

You can find the BeSafeRx information at:

https://www.fda.gov/drugs/buying-using-medicine-safely/besaferx-your-source-online-pharmacy-information

What’s changed recently

The REDEFINE trial (NEJM, 2025) studied cagrilintide combined with semaglutide (CagriSema) and showed about 20.4 percent weight loss over 68 weeks, compared with 14.9 percent with semaglutide alone; that kind of data will shape treatment algorithms going forward. GoodRx reports that the FDA’s grace period for compounding GLP-1s has officially ended for both tirzepatide and semaglutide, though some pharmacies still market “custom” or “non-identical” formulations, and regulators are watching closely.

Approach this without judgment if you’re a clinician. Patients are trying to find affordable solutions. And they often trust what they see on social media more than official channels; we can help most by staying informed, asking questions, and documenting carefully. Patients should be cautious for a different reason. Ask your provider to review any compounded medication before you use it, make sure your pharmacy meets every item on that checklist, and use resources like the FDA’s BeSafeRx to verify safety.

Knowledge and transparency remain the best safeguards.

Scott Rennie, D.O.

Board Certified in Obesity Medicine and Family Medicine

This blog is for educational purposes only and does not constitute individual medical advice. Always consult your own physician before making changes to your health, medications, or treatment plan.

Is Obesity a Brain Problem? How the Body Controls Weight

On By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Patients ask me some version of this constantly: “Why can’t I just eat less and lose the weight?” On the surface it sounds like a fair question. Obesity is a chronic disease with a great deal of biology behind it, and the brain sits at the center of that biology. Treatment that ignores this tends to fail, and the patient usually gets blamed for the failure.

Research from Dr. Sabrina Diano at Columbia University lays out how the brain regulates weight and why it matters clinically.

The central nervous system runs energy balance through two systems. The hypothalamus handles hunger and fullness, the homeostatic side. The hedonic pathway, running on dopamine, responds to reward. That second system is why cravings and emotional eating feel as forceful as they do (Lenoir et al., 2007; Samaha et al., 2020).

Within the hypothalamus, the arcuate nucleus holds two opposing groups of neurons. NPY/AgRP neurons drive eating when energy runs low. POMC/α-MSH neurons suppress appetite when energy is adequate. Both communicate with the PVN, VMH, and LH, and the result is a negotiated balance between intake and expenditure (Diano, 2024; Gropp et al., 2005).

The body feeds signals into that system constantly. Fat tissue releases leptin, which should reduce appetite, except that many patients with obesity develop leptin resistance and the signal lands blunted (Zhang et al., 1994). Adiponectin helps regulate insulin and fat metabolism, and levels fall in obesity (Mahmoud, 2022). After meals, insulin, GLP-1, PYY, and amylin generate satiety. Ghrelin, made in the stomach, climbs before meals and drives hunger. In Prader-Willi syndrome it runs abnormally high (Drucker & Holst, 2023).

Diet interferes with the signaling directly. High-fat, high-sugar foods provoke inflammation in the hypothalamus that disrupts how these neurons talk to each other, through oxidative stress and breakdown of melanocortin pathways (Kim et al., 2019; Diano, 2023). Obesity also generates low-grade inflammation throughout the body, visceral fat especially, which worsens insulin resistance (Mukherjee et al., 2023).

Genetics complicates it further. A few single-gene mutations cause obesity outright, but most cases involve many genes each nudging risk slightly. Epigenetics matters too: maternal obesity during pregnancy can alter gene expression in the child and raise their risk decades later (Farooqi et al., 2003; Mahmoud, 2022; Catalano & Shankar, 2017).

The gut microbiome is another piece, with lower microbial diversity and more gut inflammation both tracking with obesity (Vezza et al., 2020). Environmental chemicals including BPA and phthalates can disrupt hormone signaling and tilt the body toward storing fat (Heindel et al., 2015).

All of this explains the part patients find most demoralizing, which is why weight loss is so hard to hold onto. The body defends a set point. Weight comes down, metabolism slows, hunger hormones rise, and regain becomes the likely outcome (Diano, 2024).

Consider what that looks like in practice. Someone loses 20 pounds through real effort, and then finds themselves hungrier than they have ever been while burning fewer calories at rest. Nothing about their discipline changed. Their body is defending the weight it had before.

Recognizing obesity as a biologically regulated condition changes the approach. Treatment has to work on several fronts at once: nutrition, behavioral strategy, medication, and sometimes surgery. GLP-1 receptor agonists like liraglutide and semaglutide, and dual agonists like tirzepatide, act on these pathways directly, which is a large part of why they work as well as they do.

Obesity is physiology, environment, and genetics interacting. Personal choice is in there somewhere, well downstream of the rest. Understanding that gives us better tools and considerably more patience.

Scott Rennie, D.O.

References

Diano, S. Physiology and Pathophysiology of Obesity, Columbia University, 2024.

Zhang Y, et al. Nature, 1994;372(6505):425-32.

Gropp E, et al. Nature Neuroscience, 2005;8(10):1289-91.

Farooqi IS, et al. NEJM, 2003;349(6):570-8.

Drucker DJ, Holst JJ. Diabetologia, 2023;66(4):651-64.

Kim DW, et al. Cell Metabolism, 2019;30(1):110-122.

Mukherjee R, et al. Front Endocrinol, 2023;14:1154067.

Heindel JJ, et al. Nat Rev Endocrinol, 2015;11(11):653-61.

Mahmoud AM. Int J Mol Sci, 2022;23(3):1225.

Catalano PM, Shankar K. BMJ, 2017;356:j1.

Vezza T, et al. Antioxidants, 2020;9(7):578.

Lenoir M, et al. PLoS One, 2007;2(8):e698.

Samaha AN, et al. Neurosci Biobehav Rev, 2020;113:198-213.

Board Certified in Obesity Medicine and Family Medicine

This blog is for educational purposes only and does not constitute individual medical advice. Always consult your own physician before making changes to your health, medications, or treatment plan.

Doctor Supervised Weight Loss: What Works Long Term

On By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Telling patients to eat less and move more doesn’t cut it. Obesity is a chronic disease, and progress requires structured, ongoing, individualized care. The hardest part clinically is making sure the weight that comes off is fat rather than muscle.

Losing muscle costs more than strength. It costs independence, recovery capacity, and eventually survival. Older adults and patients with low baseline activity are the most exposed. Poorly managed weight loss produces sarcopenia, the loss of muscle mass and function. Layer excess fat on top and you get sarcopenic obesity, where a patient looks heavy and is functionally weak and metabolically compromised at the same time.

The European Working Group on Sarcopenia in Older People sets out how to catch it early. It starts with loss of strength, measured by grip strength or a chair-stand test. DXA or BIA can confirm low muscle mass. Poor strength plus low mass plus reduced physical performance defines severe sarcopenia. These definitions give us a framework to act before decline becomes permanent (Cruz-Jentoft et al., Age Ageing, 2019).

Muscle mass predicts survival on its own. Appendicular Lean Mass Index, lean tissue in the arms and legs divided by height squared, is a reliable measure, and people in the top quartile carry substantially lower all-cause mortality than those in the lowest, even after adjusting for BMI and comorbidities (Srikanthan & Karlamangla, Am J Med, 2014). Put plainly, a patient with stronger arms and legs has better odds of living longer regardless of what the scale says.

Strength testing matters as much as mass. Low grip strength tracks with higher mortality from cardiovascular disease, cancer, and respiratory illness. Poor lower-body strength, showing up as slower gait speed or difficulty rising from a chair, tracks with frailty, hospitalization, and long-term disability.

Both measures are cheap and fast, and both are underused. Grip strength needs a dynamometer and a hand to put it in, which rules it out of any remote encounter. The 30-second sit-to-stand doesn’t. A hard chair, arms crossed over the chest, as many stands as the patient can complete in thirty seconds, counted by whoever is watching. It works over video as well as it works in a room, and it yields a number worth tracking across visits. One usable functional measure beats a chart full of weights.

Nutrition is the cornerstone of preserving muscle during weight loss. The baseline protein RDA of 0.8 g/kg/day is inadequate for many adults, particularly older patients and anyone in a calorie deficit. The evidence supports closer to 1.2 to 1.6 g/kg/day, and up to 2.0 g/kg/day in some medically supervised cases (Paddon-Jones et al., Am J Clin Nutr, 2015; Bauer et al., J Am Med Dir Assoc, 2013). Spacing intake across meals rather than loading it at dinner sustains muscle protein synthesis better. Whey and casein, soy, eggs, and blended plant sources all work.

Calculating a target in patients with obesity is genuinely awkward. Actual body weight overshoots. Ideal body weight undershoots. Adjusted body weight is the usual compromise, and reasonable clinicians disagree about which to use. For a 5’6″ patient, a target weight around 73 kg at 1.5 g/kg puts the daily goal near 110 grams, which is a number a patient can actually work with.

Exercise has to include both resistance and aerobic work. Resistance training protects and builds lean mass. Aerobic activity improves cardiovascular and metabolic health. A 2022 systematic review and meta-analysis found the combination conferred the greatest mortality risk reduction, and notably found that weight training alone wasn’t associated with lower mortality among people doing no aerobic exercise (Shailendra et al., Am J Prev Med, 2022). For a patient that translates to brisk walking or cycling most days plus two or three weekly strength sessions using bands, weights, or bodyweight.

Think of muscle like a retirement account. Build it and hold it early, so it is there when it is needed. A patient in their seventies who lands in the hospital with pneumonia can lose a large fraction of their reserve to a few days of immobility and poor intake. If the reserve was thin going in, the decline may be permanent, and it shows up later as falls, fractures, and lost independence. Investing ahead of time changes that trajectory.

Medication is a real adjunct, and it has to be paired with strategies that protect lean tissue. GLP-1 receptor agonists produce substantial weight loss, and a meaningful fraction of that loss is lean mass. Adequate protein and resistance training are the mitigation strategies with actual evidence behind them, and body composition deserves monitoring wherever it is available rather than weight alone.

As clinicians, we need to screen past BMI. Ask about physical activity. Get a functional measure. Consider dietary adequacy. Refer to dietitians, physical therapists, or trainers where it helps, and even a single session with a trainer improves safety and confidence with resistance work. Set goals patients can hold: one to two pounds a week of fat loss while protecting muscle.

Obesity treatment is chronic care. The point is helping patients hold strength, mobility, and independence while metabolic health improves, and preserving muscle sits at the center of that.

Scott Rennie, D.O.

References:

1. Cruz-Jentoft AJ, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16-31. https://pubmed.ncbi.nlm.nih.gov/30312372/

2. Srikanthan P, Karlamangla AS. Muscle mass index as a predictor of longevity in older adults. Am J Med. 2014;127(6):547-553. https://pubmed.ncbi.nlm.nih.gov/24561114/

3. Paddon-Jones D, et al. Protein and healthy aging. Am J Clin Nutr. 2015;101(6):1339S-1345S. https://pubmed.ncbi.nlm.nih.gov/25926511/

4. Bauer J, et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J Am Med Dir Assoc. 2013;14(8):542-559. https://pubmed.ncbi.nlm.nih.gov/23867520/

5. Shailendra P, et al. Resistance Training and Mortality Risk: A Systematic Review and Meta-Analysis. Am J Prev Med. 2022;63(2):277-285. https://pubmed.ncbi.nlm.nih.gov/35599175/

Board Certified in Obesity Medicine and Family Medicine

This blog is for educational purposes only and does not constitute individual medical advice. Always consult your own physician before making changes to your health, medications, or treatment plan.