Introduction
In recent years, GLP-1 receptor agonists like semaglutide (Wegovy, Ozempic) and liraglutide (Mounjaro) have emerged as game-changers in the fight against obesity, metabolic dysfunction, and even early-stage cardiovascular diseases.
A recent UK survey of 1000 women revealed that 72% of women are considering them to help lose weight.
Their ability to curb appetite, regulate blood sugar, and promote sustainable weight loss has earned them praise and scrutiny.
There is a mixed reaction in the functional medicine community, which I can understand. I don’t think anyone can argue that the best way to lose weight is with balanced, careful dietary intake, exercise and lifestyle (stress and work) management. However, we knew all of that before they arrived on the scene. The same survey showed that 55% of women had previously committed to one or two methods with 22% having tried 3-5 methods.
That data shows the reality that many people struggle despite their best intentions. Setting aesthetics aside, being overweight not only carries a significantly increased risk of cancer, heart disease, and diabetes—the top causes of reduced health span—but also makes people miserable. It makes them less likely to be active and partake in healthy activities.
That psychological aspect of being overweight is rarely mentioned in this conversation. Many of my patients have fought with their weight all their lives; in short, it makes them miserable.
My take is that if you have tried the other options over the years then it may be a sensible approach. However, it is essential to fully understand how these medications work and avoid the pitfalls. It is a tool not a cure for the reasons you may have unhealthy eating habits. If you are considering them, it is the perfect time to address those habits and put some new ones in place.
Are we using them in the wrong way?
In the medical community, there is also an increased feeling that we may not be using these powerful drugs most healthily, and new protocols are emerging. Most of the clinical studies that have been produced have been done by drug companies and are designed in a way to demonstrate the greatest weight loss in the shortest period.
I can understand that logic; if you are producing a new drug, you want to show it is better than the competitors.
However, that may be in conflict to the "best" way to use them. New protocols are suggesting that if you do NOT try to get a fast weight loss, then the results may actually be better long term, with fewer unwanted side effects of muscle loss, skin sag and rebound. Regimens that aim to be on as low an effective dose as possible with a titration period of the drug or pulsing (increasing gaps between injections of a lower dose) may avoid these issues and offer better long-term results. To date, published data on these approaches has been limited to case reports rather than extensive studies. In my own practice, I have seen this approach work better.
Muscle loss- the risk you need to know about and take action to avoid
One of the main reasons I wanted to write this blog is that many people are unaware of what I feel is a major issue with them: muscle loss.
Maintaining muscle bulk is essential for many reasons. For one, it accounts for around 70% of glucose consumption in the body, if you want to keep weight off and maintain metabolic health you want plenty of muscle around to keep this in check.
When on GLPs, there are ways to minimise this, and I would strongly recommend you read on if you are considering this weight loss treatment.
Some studies have shown that 40-60% of weight loss is not fat loss, but muscle loss. There is doubt around this as some of what appears to be muscle loss may be fat inside muscle ie the fatty parts you see in some cuts of meat when cattle have been fattened up.
Maintaining muscle bulk is critical as we age, and with the right regimen, it is actually possible to increase muscle bulk while losing fat on GLP-1 therapies if you are careful in your approach.
Why muscle loss happens with GLPs
When you lose weight rapidly, your body isn’t just burning fat; it often breaks down muscle tissue for energy. The appetite suppression caused by GLP-1 drugs usually means you’re not eating enough calories to meet your body’s daily energy needs. Several key factors contribute to this muscle loss:
Caloric deficit and muscle catabolism:
When insufficient energy intake, the body breaks down muscle protein (amino acids) as an alternative fuel source. This is especially problematic if dietary protein intake is low.
Reduced physical activity:
Low-calorie states can cause fatigue and decreased motivation to exercise. Without resistance training, the body’s natural tendency is to conserve energy by breaking down less-needed muscle tissue.
Inadequate protein intake:
When calorie intake is low, consuming enough protein to signal muscle protein synthesis becomes critical. Without sufficient protein, the body turns to muscle stores for amino acids.
Cellular hydration and muscle preservation:
Muscle cells are 70-75% water, and adequate cellular hydration is crucial for maintaining muscle volume and function. Dehydration impairs nutrient delivery and exacerbates muscle breakdown.
Key strategies to prevent muscle loss
1. Prioritise protein intake, but not just any protein
Protein is essential for muscle repair and growth, especially during weight loss. Aim for 1.6 to 2.0 grams of protein per kilogram of body weight daily to support muscle preservation.
Whey protein:
Whey protein is a fast-absorbing, high-quality protein source rich in essential amino acids, particularly leucine, critical for triggering muscle protein synthesis. It also increases IGF-1, critical for muscle growth in a way that plant proteins do not, a bit of a hidden super-power, which is why it is so loved by the body-building community.
Tip: Include 20-30g of whey protein per serving to stimulate muscle repair effectively.
Example: Blend whey protein with almond milk, a banana, and spinach for a muscle-preserving smoothie.
BCAAs (branched-chain amino acids):
BCAAs (leucine, isoleucine, and valine) are directly metabolised by muscle cells, making them effective at reducing muscle breakdown during calorie restriction.
Tip: Supplement with 5-10g of BCAAs pre-workout or during extended periods between meals.
2. Resistance training- A MUST
Strength or resistance training is essential for maintaining muscle mass during weight loss. If you are not doing this already, you really need to add it to your regime.
Aim for 3-4 sessions per week with compound movements (e.g., squats, deadlifts, push-ups).
Include progressive overload, gradually increasing the weight or resistance to continue building strength.
Resistance training also improves insulin sensitivity, which complements the metabolic benefits of GLP-1 medications.
3. Maintain cellular hydration ADD electrolytes- vitally essential and often overlooked
Dehydration can impair muscle function and promote catabolism. Studies have shown that maintaining cellular hydration is key to maintaining muscle strength. That doesn't mean water, it means water with electrolytes
Electrolyte balance: Focus on fluids containing sodium, potassium, magnesium, and calcium.
Hydration timing: Sipping water consistently throughout the day (aim for 2-2.5 litres daily) is better than glugging pints at a time.
Hydration sources: Include water-rich foods like cucumbers, watermelon, and leafy greens.
4. Leverage creatine for muscle preservation
Creatine promotes cellular hydration and muscle strength.
Dosage: Take 3-5g of creatine monohydrate daily to support workouts and muscle recovery.
5. Nutrient timing: Feed muscles at the right time
Consume protein-rich meals within 30-60 minutes post-workout.
Distribute protein evenly throughout the day.
6. Key nutrients to support muscle preservation on GLP-1 therapies
- L-Carnitine (500-1,000 mg/day): This supplement enhances fat metabolism and energy production, reducing muscle fatigue and protecting lean body mass during weight loss.
- Omega-3 Fatty Acids (1,000mg day of EPA + DHA): Anti-inflammatory properties help reduce muscle breakdown, promote protein synthesis, and support joint and cardiovascular health.
- Magnesium (200-400 mg/day): Crucial for energy production, muscle contraction, and hydration, preventing muscle cramps and fatigue.
- Vitamin D3 (4000 IU/day with K): Supports muscle strength, calcium absorption, and recovery, reducing the risk of muscle weakness during weight loss.
- Zinc (15/day): Aids protein metabolism, muscle repair, and immune function while supporting hormonal balance for muscle preservation.
Why L-carnitine and Omega-3 Are Critical
L-carnitine is a key player in optimising fat metabolism by transporting fatty acids into mitochondria for energy production, known as the carnitine shuttle; it helps preserve muscle tissue while promoting fat loss. As calorie intake decreases on GLP-1s, maintaining efficient energy production is essential to prevent muscle catabolism and fatigue. Similarly, omega-3 fatty acids reduce inflammation and muscle breakdown while enhancing muscle protein synthesis, making them crucial for preserving lean mass.
Magnesium, vitamin D, and zinc fill the common nutrient gaps caused by appetite suppression on GLP-1s. Together, they support cellular hydration, muscle contraction, energy production, and recovery, ensuring muscle preservation and overall metabolic balance.
7. Avoid prolonged periods of low-calorie intake
Incorporate periodic refeed days at least twice a week to replenish glycogen stores, prevent metabolic slowdowns, and protect muscle tissue. If you struggle with larger meals having several smaller meals through the day can help.
One approach some Doctors take is to space injections out more than 7 days to allow a greater intake in days 8-10. That sounds sensible however no data has yet been published on this approach.
8. Monitor body fat percentage not weight.
Use body composition analysis to ensure weight loss comes primarily from fat, not muscle. Lots of gyms have scales that allow you to get a better insight in to body make-up. BMI is a notoriously poor way of measuring this. Professional rugby players often have BMIs in the high 30's with body fat percentages in single digits, it's not a good way of measuring fat loss.
Final thought: Muscle preservation is key to long-term success
Losing weight without protecting your lean muscle can lead to metabolic slowdown, making it easier to regain fat once the medication is stopped.
When the body is in a hypo-caloric state, appetite surges afterwards. Weaning slowly off these drugs, changing to a high-protein diet and being mindful of the reasons you eat can help all of these things.
During treatment focusing on protein intake, resistance training, hydration, and proper supplementation can minimise muscle loss and set the foundation for sustainable weight maintenance. When done right, you’ll achieve a leaner body and a healthier, stronger, and more resilient one.
About the author: Dr Geoff Mullan is a Functionally trained medical Doctor in the UK. His interests involve longevity and healthspan.
Disclaimer: All of this article's comments are the opinion of Dr Mullan. They do not constitute medical advice.
References
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- Wilkinson TJ, Papamargaritis D, King JA, Sargeant JA, Sutcliffe C, Baker LA, Taheri S, Yates T, Davies MJ. Preservation of healthy lean body mass and function during weight loss. Clin Obes. 2024 Aug;14(4):e12683. doi: 10.1111/cob.12683. Epub 2024 May 23. PMID: 38783586.
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