Another Weighty Issue: Why Isn’t There a Muscle GLP-1?

BOTTOM LINE

While researching my weighty blog on GLP-1s, I found myself being nagged by another question:

GLP-1s have become the celebrity drugs in current medicine, prescribed to improve metabolic health, with newer versions making regular appearances.

Yet, curiously, another important aspect of metabolic health receives far less attention.

Lean muscle mass.

This struck me as odd because muscle isn’t simply there to move us around and lift heavy things. It is one of the body’s most metabolically active organs (find out why here)

If healthy metabolism depends on both reducing excess visceral fat and preserving lean muscle mass, then why has so much attention—and investment—been directed towards drugs that help us lose fat, while comparatively little seems to be aimed at helping us preserve or build muscle?

After all, GLP-1 medications and many anabolic therapies began life in much the same way: they were developed to treat recognised medical conditions. Like Botox, Viagra and Zyban, GLP-1s and anabolic therapies later found uses well beyond their original purpose.

So why has one become a medical success story while the other remains largely confined to specific medical conditions—or “hidden” in the world of elite sport and bodybuilding?

I think the answer might lie in what happens when these drugs are used outside their intended purpose.

GLP-1s are primarily prescribed to restore healthier metabolic function in people with recognised metabolic disease. Used appropriately and under medical supervision, the benefits generally outweigh the risks.

By contrast, when anabolic therapies are used simply to build more muscle in an otherwise healthy person, the goal is no longer restoration, but enhancement—pushing muscle growth beyond what the body would ordinarily achieve. Enhancing physiology past restoring it seems to come with a less favourable risk-benefit balance.

That said, muscle preservation has certainly not been ignored: researchers are developing treatments that aim to preserve muscle while restoring metabolic health during weight loss. They may eventually change the landscape.

For now, however, there is no safe quick fix to maintain and build your lean muscles.

You still have to do the hard yards.

HOW TO BUILD AND PRESERVE LEAN MUSCLE MASS

If you are considering supplements or anabolic therapies to help build or preserve muscle, start with this question:

Am I trying to restore normal physiology or exceed it?

If the aim is to correct a genuine deficiency or treat a recognised medical condition, the benefits may outweigh the risks. If the aim is to push a healthy body beyond its normal physiological limits, the risk-benefit balance usually becomes much less favourable.

Second, build the foundations before looking for additions:

The good news is that your body already comes with an extraordinarily effective muscle-building system.

• Do your progressive resistance training at least twice weekly.
• Recover sufficiently after exercise.
• Ensure your daily protein intake is 1.2–1.6 g /kg/day.
• Keep up all the other good lifestyle things like cardio, sleep, stress management.

Then if you want to add more, think of the additional options as sitting on a spectrum:

At one end are nutritional supplements such as creatine monohydrate and essential amino acids (EAAs), which may provide modest additional benefits when combined with resistance training and generally have favourable safety profiles.

Further along the spectrum are prescription hormone replacement therapies, which can be highly beneficial for people with genuine deficiencies, but are not intended for otherwise healthy individuals.

Beyond these lie anabolic androgenic steroids (AAS), growth hormones (GH) and Selective Androgen Receptor Modulators (SARMs). These can certainly increase muscle mass, but they do so with progressively greater biological costs and increasingly unfavourable risk-benefit profiles.

EXPLORE THE EVIDENCE

Jump to the topic that interests you most, or simply read on.

Lifestyle first

• Why muscle matters
• Resistance training & protein

Supplements

• Creatine
• Essential Amino Acids (EAAs)
• Vitamin D & Omega-3s

Hormone replacement

• Testosterone Replacement Therapy (TRT)

Performance-enhancing therapies

• Anabolic Androgenic Steroids (AAS)
• Growth Hormone (GH) & IGF-1
• Selective Androgen Receptor Modulators (SARMs)

Harking back to my previous blog, these are some of the many reasons why lean muscle mass matters:

Before disappearing down the supplement aisle, remember that skeletal muscle is already extraordinarily responsive to progressive resistance training, sufficient protein, adequate recovery, sleep and stress management. These things remain the interventions with the strongest evidence and the lowest risk.

Supplements, which have not been shown to have great lean muscle mass gains, but carry a relatively low risk profile include:

Creatine is a naturally occurring compound found in our cells and derived from 3 EAA’s (arginine, glycine, and methionine).

If ATP, the main fuel your cells use for energy, were your phone battery, creatine would be your additional power bank. It won’t give your phone a bigger battery—it simply helps recharge it when the battery icon starts flashing red.

This is most handy when it comes to intense physical and mental activity. Creatine has been shown to improve muscle protein synthesis, power, strength and recovery. In fact, it has many other neat benefits beyond the scope of this blog.

There are many online voices discussing the impact of creatine use and of course there are therefore as many contradictory “expert” opinions. Luckily, in May 2026, Naddafha et al conducted a systematic review of randomized, placebo-controlled trials examining creatine supplementation, with or without resistance training (RT), in postmenopausal women, a review which helps to put a full stop behind the real truth:

“In postmenopausal women, creatine,  …  with RT, yields small but meaningful gains in lean mass and strength” (Naddafha et al, 2026, Conclusion)

So, if you are postmenopausal and you are going to take it, you still have to do the resistance training to make it worth your while. But do be wary of the overhyped marketing of creatine, because the gains with respect to lean muscle mass are small.

If you are younger (than postmenopausal😉), adding creatine to a good resistance-training programme can produce slightly greater gains in muscle and strength than training alone—typically around 5–10% more improvement.

Some say that creatine supplementation may come with early weight gain as water is retained within muscle. Some say it doesn’t – the reviewed evidence is mixed!

In the end though, creatine isn’t pixie dust. It still expects you to lift the weights.

The 20 amino acids are organic molecules that your body uses for all kinds of critical jobs. Of the 20, 9 are essential because we do not make them ourselves, so we have to get them from food or supplements. When the EAAs are combined with resistance training, they promote muscle protein synthesis which, in turn, increases muscle mass, strength, function and quality. EAA’s also help with muscle repair and recovery and muscle repair.

A 2026 meta-analysis (read: a study of many studies with lots of subjects in them) of the effect of Vitamin D supplementation on body composition in older adults (60+) found little evidence that supplementation alone increases muscle mass or strength. It may help if paired with resistance training and increased protein and calcium intake. Similarly, a 2025 meta-analysis investigating whether Omega 3 fatty acid supplementation enhanced or maintained skeletal muscle mass, strength, and physical function found limited evidence that it was effective across either younger or older adults or prevents the loss of lean muscle mass.

To restore clinically diagnosed missing lean muscle mass, you can turn to hormone replacement:

Testosterone is one of the body’s key anabolic (“building up”) hormones, in both men and women. It helps maintain bone density and stimulate muscle protein synthesis , which contributes to increased lean muscle mass and reduced fat mass.

It’s easy to see why testosterone has earned almost mythical status in the fitness world.

In older men with clinically low testosterone levels, testosterone replacement therapy (TRT) has been shown to increase lean muscle mass, reduce fat mass and produce modest improvements in strength.

The important word here is replacement.

Restoring testosterone isn’t as simple as writing a prescription and admiring your new biceps. Once you start changing hormone levels, the rest of your body has an opinion too. That’s why TRT requires ongoing medical supervision.

As these health risks of using testosterone are pretty generic to the other androgen therapies to be discussed, I’ll summarise them all here. Additional risks pertaining to a particular therapy will be discussed there.

For the ladies, the picture is rather different. An international consensus statement endorsed by numerous organisations, including the Endocrine Society, the International Menopause Society, the North American Menopause Society, and several others concluded that the only evidence-based indication for testosterone therapy in women is for the treatment of hypoactive sexual desire disorder (HSDD) in selected postmenopausal women.

Importantly, the same consensus statement found no statistically significant improvement in lean muscle mass, total body fat or muscle strength with physiological testosterone therapy. In addition, long-term safety data beyond 24 months are lacking.

That grey area

Spend five minutes on social media and you’ll quickly find doctors, menopause specialists and coaches recommending testosterone for reasons that extend well beyond current guidelines.

This is one of those areas where I don’t think medicine has neat edges. Researchers are rightly guided by what the evidence shows across large populations. Clinicians, however, have to make decisions for one person at a time, taking into account symptoms, medical history, examination findings and personal goals.

This is particularly relevant to hormone reference ranges: a physically active 40-year-old farmer in Zambia may have a very different physiological baseline from a sedentary 20-year-old university student in the UK. “Normal” is therefore not always quite as absolute as we’d like it to be.

For that reason, some clinicians may prescribe testosterone off-label when they judge the potential benefits to outweigh the risks, while others adhere more closely to published guidelines. In my view, neither approach is necessarily incompatible with good medicine—they simply reflect different ways of applying evidence to individual patients.

Whatever side of the guideline debate you sit on, starting testosterone because someone at the gym—or on TikTok—said it was a good idea is still a terrible plan.

Pushing beyond normal physiology with performance enhancing anabolic therapies.

Synthetic versions of testosterone designed to exaggerate its muscle-building effects, because they:

• stimulate muscle protein synthesis
• reduce muscle break down
• increase muscle stem (satellite) cell activity
• increase the number of circulating red blood cells

The result is exactly what you’d expect: muscles grow faster, recovery is quicker and training adaptations happen more rapidly. Because AAS deliberately push testosterone signalling well beyond normal physiological levels, they can produce impressive increases in muscle size—even without resistance training.

Awesome – a quick fix!

Except that ….

The very reason AAS work so well is also why they carry such a high biological cost. Many of the risks are the same as those discussed under TRT, only amplified because the doses are often far higher than those used medically. AAS also come with some additional risks, including:

For men:

• prostate concerns
• shrinking testicles
• reduced sperm production and fertility
• male-pattern baldness
• possible increased risk of testicular cancer

For women:

• permanent voice deepening
• reduced breast size
• increased body hair growth
• vaginal dryness and irritation
• menstrual disturbance

To be fair, AAS are not simply “bodybuilding drugs”. They remain valuable medications for certain medical conditions, including muscle wasting associated with cancer or AIDS, hypogonadism, some breast cancers, osteoporosis and endometriosis. In these situations, the aim is to restore health—not create superhuman physiques.

GH and IGF-1 are something of a double act. GH, produced by the pituitary gland, stimulates the production of IGF-1, and together they regulate growth, tissue repair, body composition and fat metabolism. During childhood they drive normal growth; in adults they continue to help maintain and repair tissues. It’s easy to see why they’ve become favourites in the muscle-building world. The trouble is that, outside of a genuine deficiency, the evidence is considerably less impressive than the marketing. Although they can increase lean muscle mass, that doesn’t automatically translate into greater strength or better physical function.

Synthetic GH (somatropin) is an approved treatment for medically diagnosed GH deficiency, muscle wasting associated with AIDS and short bowel syndrome. Outside of these recognised indications, however, the balance between benefit and risk becomes much less favourable. And, in the world of professional and elite sports, GH and IGF-1 are prohibited substances.

One way to understand the potential risks of taking GH and IGF-1 is to look at acromegaly, a condition caused by excessive production of these two hormones. People with acromegaly develop enlarged hands, feet and facial features, along with many of the metabolic and cardiovascular problems associated with excess hormone exposure. In otherwise healthy adults taking GH, recognised risks include: swelling, joint and muscle pain, Carpal Tunnel Syndrome, increased insulin resistance, high blood sugar, Type 2 Diabetes, possible cancer concerns, intracranial hypertension, and monitoring concerns in people with previous tumours.

Perhaps the biggest concern is that nobody yet knows what years of supraphysiological GH exposure may ultimately do.

One has to wonder if it is worth taking GH or IGF-1 for aesthetic purposes or improved sporting performance given all the possible side effects. This is not a harmless shortcut to preserving muscle, because unfortunately, our bodies have an irritating habit of refusing to grow only the bits we’d like it to.

SARMs are synthetic drugs designed to activate the same androgen receptors as testosterone and anabolic steroids—but more selectively.

In fairness, the original idea was actually rather clever. Researchers hoped SARMs could produce the muscle- and bone-building benefits of testosterone while minimising its unwanted effects on tissues such as the prostate, skin and hair. They were investigated as possible treatments for:

• age-related muscle loss (sarcopenia)
• cancer-related muscle wasting
• osteoporosis
• frailty
• hypogonadism

To some extent, they succeeded. SARMs do increase lean muscle mass. The problem is that these gains have not consistently translated into meaningful improvements in strength or physical function. Despite more than two decades of research, no SARM has been approved by major regulators, such as the FDA, for increasing muscle mass or enhancing athletic performance.

That hasn’t stopped them becoming popular with bodybuilders and recreational gym users, largely because they’re marketed as the best of both worlds:

• build muscle like steroids

• burn fat

• fewer side effects

• no injections

Unfortunately, the evidence doesn’t quite live up to the advertising. Many users don’t actually know what they’re taking, because commercially available SARMs are poorly regulated and products frequently contain ingredients that don’t match their labels.

The FDA (2026) was unusually blunt: “Although the products are generally marketed as dietary supplements, they are not dietary supplements. Instead, these products are unapproved drugs that FDA has not reviewed for safety and effectiveness”

Their risks overlap considerably with those of testosterone and AAS, with some additional concerns including:

• Sexual dysfunction, infertility, testicular shrinkage
• Tendon injuries
• Psychosis/hallucinations
• Pregnancy miscarriage

To make matters worse, many recreational users take doses well above those studied clinically and often combine several SARMs (“stacking”), making the already limited safety data even less applicable.

Which brings me back to something I wrote in my GLP-1 blog: if you’re taking muscle-enhancing drugs for aesthetic reasons to attract the sexual interest of another person, you may be falsely advertising the product.

To be fair, anabolic therapies may currently be somewhat underappreciated in medicine because they’ve become so closely associated with performance enhancement. If muscle loss itself eventually becomes recognised and treated more as a disease process, anabolic therapies may well have a larger role in carefully selected patients.

One of the most exciting areas of current research is combining GLP-1 medications with drugs that help preserve—or even increase—muscle while fat is being lost. You may soon start hearing names such as Bimagrumab and Apitegromab, both of which are currently in the early stages of research.

Rather than behaving like anabolic steroids, these drugs work in a completely different way. Think of myostatin and its related signalling pathways as the body’s natural muscle brake. Anabolic steroids work by pressing harder on the accelerator. Rather than flooring the accelerator, researchers are seeing what happens if they simply take the foot off the brake, allowing muscle to be preserved while fat is being lost.

Anabolic steroids are not routinely paired with GLP-1 therapy, because they don’t just act on muscle—they affect many other tissues throughout the body. Using them simply to preserve muscle during weight loss would generally expose patients to risks that outweigh the likely benefits.

Which brings us back to the question that started this blog.

Perhaps that’s why did GLP-1 medications become the celebrity drugs of modern medicine while muscle-building drugs did not.

Until anabolic therapies can preserve muscle without paying such a high biological price, there still doesn’t appear to be a risk-free shortcut to building or preserving lean muscle mass.

For now, you’ll still have to do the hard yards.

Biology, it seems, remains wonderfully resistant to shortcuts.

References with supporting statements