Protecting Muscle on GLP-1s: What to Know About HMB

GLP-1 medications like semaglutide (Ozempic®, Wegovy®) and tirzepatide (Mounjaro®, Zepbound®) have transformed how we treat obesity and metabolic disease. The results can be remarkable. But there's a quieter conversation happening among clinicians that every patient on these medications deserves to be part of: not all the weight you lose is fat.

Studies of semaglutide and tirzepatide consistently show that 25 to 40 percent of the total weight lost comes from lean mass — primarily muscle, along with smaller contributions from bone and organ tissue.¹ For a patient who loses 40 pounds, that can mean 10 to 16 pounds of lean tissue gone alongside the fat. Some of that is expected and healthy. But when it happens too quickly, in older patients, or in patients who aren't eating enough protein or using resistance training, it can set the stage for sarcopenia (age-related muscle loss), frailty, and a slower metabolism that makes keeping the weight off harder.

This post is about what you can do about it — and specifically, where a supplement called HMB might fit in.

First, the things that matter most

Before we talk about any supplement, I want to be clear that the two interventions with the strongest evidence for preserving muscle during weight loss are:

1. Eating enough protein. The target I recommend for patients on GLP-1s is roughly 1.6 to 2.2 grams of protein per kilogram of ideal body weight per day — higher than the general adult guideline, because GLP-1 patients are in a sustained caloric deficit that is more catabolic than typical weight maintenance.² For a patient with an ideal body weight of 150 pounds, that's roughly 110 to 150 grams of protein daily. Distributed across meals, that looks like 30–50 grams per sitting — about the amount in a palm-sized portion of chicken, fish, Greek yogurt with protein powder, or a protein shake. 

As with HMB, there are no head-to-head trials of protein targets specifically in GLP-1 patients; the higher target is extrapolated from caloric-deficit research in athletes and is increasingly adopted in clinical obesity medicine.

2. Some form of resistance training. Even two short sessions per week of bodyweight exercises, resistance bands, or light weights has a larger muscle-preservation effect than any supplement on the market.

These two things — protein and resistance — are the foundation. Nothing replaces them.

But here's the clinical reality I see every week in my practice: GLP-1 medications work by suppressing appetite. That's the whole point. Many patients genuinely cannot stomach 100+ grams of protein per day, especially in the first few months. And many patients — for reasons ranging from joint pain to medical limitations to life circumstances — are not going to start a strength-training program right now, even when we talk about it.

For those patients, the conversation should move to: given where you actually are, what else can we do?

That's where HMB comes into the conversation.

What is HMB?

HMB stands for beta-hydroxy-beta-methylbutyrate. It's a metabolite — a breakdown product — of the amino acid leucine, which is one of the building blocks of muscle protein.³ Your body already produces small amounts of HMB naturally when you eat protein-rich foods. HMB supplements simply provide more of it in a concentrated form.

HMB works through two main mechanisms: it appears to slow the rate at which muscle breaks down, and to a lesser extent supports the machinery that builds new muscle.⁴ In other words, it doesn't make you grow muscle out of thin air — it helps protect the muscle you already have from wasting away during catabolic (breakdown) stress.

That distinction matters. HMB is not a muscle-building supplement for healthy people going to the gym. The evidence there is underwhelming.⁵ Where HMB has its strongest and most consistent research support is in populations experiencing involuntary muscle loss — and that's exactly the situation many GLP-1 patients find themselves in.

The research 

I want to walk through what the science actually says, because there's a lot of information out there in both directions. 

Where HMB has clear evidence

Bed rest and forced immobility in older adults. A landmark 2013 study by Deutz and colleagues took healthy older adults (ages 60 to 76) and put them on 10 days of complete bed rest. The placebo group lost an average of 2.05 kilograms (about 4.5 pounds) of total lean body mass in just 10 days. The group taking 3 grams of HMB daily essentially maintained their muscle, losing only 0.17 kg on average.⁶

Sarcopenia and frailty in older adults. A 2025 meta-analysis of 21 randomized controlled trials involving 1,935 adults over age 50 found that HMB supplementation produced statistically significant improvements in handgrip strength and physical function measures.⁷ A separate 2019 meta-analysis looking specifically at HMB in clinical conditions involving muscle wasting found that HMB improved both muscle mass and strength, though the authors noted the effect sizes were modest and called for higher-quality trials.⁸

Clinical muscle wasting. Research in populations with cancer cachexia, critical illness, and post-surgical recovery has shown HMB can help preserve muscle during periods of high catabolic stress.⁹

Where HMB's evidence is weak

Healthy young adults and trained athletes. Meta-analyses in these populations have consistently shown trivial or no benefit.⁵ If you're 30 years old and lifting weights three times a week while eating plenty of protein, HMB is not going to do much for you.

What we don't have yet

There are no published randomized controlled trials of HMB specifically in patients on GLP-1 medications. The case for HMB in this population is built on the studies looking at bed-rest, sarcopenia, and clinical-wasting research — populations that share the same underlying problem (muscle loss driven by catabolic stress, low protein intake, and/or inactivity) but none are specific to GLP-1 patients.

Who HMB might help

Based on the evidence and the patients I see in my practice, HMB may be worth considering if you fall into one or more of these groups:

• You're over 50 and on a GLP-1 medication

• You're consistently eating less than 80 grams of protein per day and can't get higher despite trying

• You're not currently doing any resistance training and don't realistically see yourself starting in the near term

• You've lost weight quickly and are concerned about losing strength

• You have a personal or family history of frailty, falls, or osteoporosis

• You're a cancer survivor, post-surgical patient, or recovering from a period of immobility

If you're younger, already eating adequate protein, and strength training regularly, HMB probably isn't worth the money for you. 

If you do decide to try it

Dose. The dose used in the research is 3 grams per day, typically split into two or three doses with food.⁶ Higher doses have not been shown to provide additional benefit.

Form. HMB comes in two forms: calcium HMB (the form used in most of the research, including the Deutz bed rest study) and HMB free acid. Calcium HMB is more widely available and more affordable, and is the form I generally suggest unless there's a specific reason to choose otherwise.

Duration. Benefits appear to build over weeks, not days. If you're going to try it, commit to at least 8 to 12 weeks before evaluating.

Safety. HMB has an excellent safety profile across decades of use. No significant adverse effects have been reported in healthy or clinical populations at the studied doses.¹⁰ That said, as with any supplement, talk to your medical provider before starting — especially if you're on other medications, have kidney disease, or are pregnant or breastfeeding.

A note on expectations. HMB won't melt fat, won't replace exercise, and won't compensate for very low protein intake. It's a helper, not a substitute.

Other supplements worth knowing about

I still recommend creatine monohydrate for GLP-1 patients. It has strong evidence, including promising evidence in women, is less than a dollar a day, and helps preserve lean mass during caloric deficit.¹¹ For many patients, creatine is the first choice — but the two can be used together. 

The bottom line

GLP-1 medications are powerful tools, and they're changing lives. But they work best when paired with a strategy to protect the muscle and strength you've spent your whole life building.

The foundation is always protein and movement. When those aren't fully achievable — and in real life, they often aren't — HMB is a reasonable, well-tolerated, evidence-supported adjunct for the right patient, particularly older adults and those at risk of sarcopenia.

If you want to talk through whether HMB makes sense for your specific situation, that's exactly what our visits are for. Talk to your provider or schedule a visit at SilenceMed.Com.

Alexis Silence is an Advanced Practice Registered Nurse (APRN) and Family Nurse Practitioner (FNP-C) licensed in Arizona and Colorado. She is the founder of Silence Medical PLLC, a cash-pay telemedicine practice focused on GLP-1 weight loss and concierge care.

This post is for educational purposes and does not constitute individual medical advice. Supplements, including HMB, should be discussed with your healthcare provider before starting. Statements about supplements have not been evaluated by the Food and Drug Administration. HMB is not intended to diagnose, treat, cure, or prevent any disease.

References

1. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002. https://www.nejm.org/doi/full/10.1056/NEJMoa2032183 Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. https://www.nejm.org/doi/full/10.1056/NEJMoa2206038

2. Longland TM, Oikawa SY, Mitchell CJ, Devries MC, Phillips SM. Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: a randomized trial. Am J Clin Nutr. 2016;103(3):738-746. https://ajcn.nutrition.org/article/S0002-9165(22)06559-5/fulltext

3. Wilson JM, Fitschen PJ, Campbell B, et al. International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB). J Int Soc Sports Nutr. 2013;10(1):6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568064/

4. Holeček M. Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions. J Cachexia Sarcopenia Muscle. 2017;8(4):529-541. https://onlinelibrary.wiley.com/doi/10.1002/jcsm.12208

5. Jakubowski JS, Nunes EA, Teixeira FJ, et al. Supplementation With the Leucine Metabolite β-Hydroxy-β-Methylbutyrate (HMB) Does Not Improve Resistance Exercise-Induced Changes in Body Composition or Strength in Young Subjects: A Systematic Review and Meta-Analysis. Nutrients. 2020;12(5):1523. https://www.mdpi.com/2072-6643/12/5/1523

6. Deutz NEP, Pereira SL, Hays NP, et al. Effect of β-hydroxy-β-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults. Clin Nutr. 2013;32(5):704-712. https://pubmed.ncbi.nlm.nih.gov/23514626/

7. Li N, Chen S, He Y, et al. Effects of oral supplementation of β-hydroxy-β-methylbutyrate on muscle mass and strength in individuals over the age of 50: a meta-analysis. Front Nutr. 2025;12:1522287. https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1522287/full

8. Bear DE, Langan A, Dimidi E, et al. β-Hydroxy-β-methylbutyrate and its impact on skeletal muscle mass and physical function in clinical practice: a systematic review and meta-analysis. Am J Clin Nutr. 2019;109(4):1119-1132. https://pubmed.ncbi.nlm.nih.gov/30982854/

9. Prado CM, Orsso CE, Pereira SL, Atherton PJ, Deutz NEP. Effects of β-hydroxy β-methylbutyrate (HMB) supplementation on muscle mass, function, and other outcomes in patients with cancer: a systematic review. J Cachexia Sarcopenia Muscle. 2022;13(3):1623-1641. https://onlinelibrary.wiley.com/doi/10.1002/jcsm.12952

10. Fitschen PJ, Wilson GJ, Wilson JM, Wilund KR. Efficacy of β-hydroxy-β-methylbutyrate supplementation in elderly and clinical populations. Nutrition. 2013;29(1):29-36. https://pubmed.ncbi.nlm.nih.gov/23085015/

11. Candow DG, Chilibeck PD, Forbes SC. Creatine supplementation and aging musculoskeletal health. Endocrine. 2014;45(3):354-361. https://link.springer.com/article/10.1007/s12020-013-0070-4