Several powerful drugs have been developed that can promote weight loss. These are peptides that target receptors in the body that control metabolism and behaviour.  But how exactly are these drugs affecting body weight and why might this matter?

This article will go over the importance of body composition over simply measuring body weight, the function of each of the tissues used for these measurements and the influence of weight loss peptides on the body.

BMI and Body Composition

We will begin by looking at measurements that have been used to determine health and what these measurements actually tell us.

BMI: An Outdated Measurement

For many decades, the Body Mass Index (BMI) has been used to determine whether someone is a healthy weight or not. You simply divide your weight in kilograms by your height in metres squared and you get the number that is your BMI. If the number falls between 18.5 and 24.9, you are healthy, anything below or above that is considered unhealthy.

This way of determining healthy weight has been criticised by many, most notably those who build high muscle mass. BMI measurements tend to label these people as overweight despite their lack of adipose (fat) tissue. The BMI’s lack of versatility means that we would benefit from assessing health using different measurements¹. Research has found that by looking at body composition, we can get a more reliable idea of someone’s health.

What The Body is Composed of

When looking at body composition, we are taking into consideration the percentage of muscle, fat, bone and water that make up the body’s weight. These percentages can give us a good indication of the overall metabolic health of the body. It is a far more accurate indicator of health than BMI. These percentages tell us a lot about the state the body is in:

• Water: This is vital for the body to function properly. Too much indicates water retention, while too little indicates dehydration.
• Bone: High bone density is favourable since, as we age, we tend to lose bone. Without enough bone density built up in our younger years, we are at risk of osteopenia and osteoporosis in later life.
• Muscle: More muscle indicates higher levels of activity, both of which are linked to improved health.
• Adipose tissue: This is the body’s reserve of energy. This can be tapped into during periods of fasting or exertion and generates heat to regulate body temperature.

In addition to this, the bones, muscle and adipose tissue also act as endocrine organs, secreting hormones that influence various aspects of the body’s functioning. The levels of hormones that are secreted by each of these tissues are affected by how much of them we have. They also influence one another, so by looking at body composition, we gain insight into metabolic health.

Muscle, Fat and Bone Hormones

Each of these tissues secretes hormones that affect the way the body functions. We will briefly look at what these tissues are secreting and how they can affect one another.

Muscle

Muscles secrete a variety of myokines, some of the most notable include:

• Interleukin 6 (IL-6): Increases dramatically during exercise and influences metabolism and inflammation².
• Irisin: Promotes thermogenesis in adipose tissue³.
• Myostatin: Influences the ability of muscles to adapt to exercise⁴.
• IGF-1and FGF-2: These are involved in muscle hypertrophy and bone formation⁵.
• Metrnl: Affects metabolism and increases insulin sensitivity⁶.

Adipose Tissue

Adipose tissue secretes adipokines, such as:

• Leptin: Regulates appetite and energy balance. Those who are overweight often suffer from leptin resistance⁷.
• Adiponectin: Enhances insulin sensitivity and has anti-inflammatory effects. Levels are decreased in those with obesity⁸.
• Resistin: Linked to insulin resistance⁹.
• Plasminogen activator inhibitor-1 (PAI-1), angiotensinogen and inflammatory cytokines: These are often produced by resident macrophages in adipose tissue. In obesity, adipose tissue becomes a major source of low-grade inflammation¹⁰.

Bone

Bone tissues secrete hormones called osteokines, including:

• Osteocalcin: Enhances insulin secretion and sensitivity, influencing glucose metabolism. It can also affect testosterone production, brain function and cognition¹¹.
• Fibroblast Growth Factor 23 (FGF23): Acts on the kidneys to regulate phosphate metabolism¹².
• Sclerostin: Involved in bone remodelling¹³, energy metabolism and adipose tissue expansion and browning.
• Lipocalin-2: Suppresses appetite¹⁴.

This list is not exhaustive and does not fully cover the vast effects of each of these hormones, as each deserves its own article. This brief overview aims to put into perspective the influence that these tissues can have on hormones and each other.

How well developed each of these tissue types can give us clues as to how well they function as endocrine organs. There is an optimal body composition and an imbalance in this can lead to dysregulation of homeostasis and poor health outcomes.

What Does a Healthy Body Composition Look Like?

Based on the function of each of these tissues, we can see that there is great benefit in maintaining muscle mass, promoting bone formation and controlling adiposity.

Muscle mass greatly helps in regulating glucose and lipid metabolism, with greater muscle mass being linked to positive health outcomes. The exercise that stimulates muscle growth also promotes bone formation, as such, greater muscle mass is linked to healthier bone density.

Since increased adiposity can lead to resistance or decline in healthy hormone secretion and increased inflammation, this is one tissue we do not want to promote the growth of. We need adipose tissue at healthy levels for its beneficial role in health, but this must be carefully controlled. Ideally, men in their 20s and 30s would have approximately 10-20% body fat, for women, 20-30% fat is considered healthy.

Factors That Affect Body Composition

Body composition is affected by several lifestyle factors, perhaps the most prominent being your diet and exercise habits.

Diet

Food plays a significant role in your body composition. A calorie deficit can lead to fat loss, while a surplus can support muscle gain if combined with physical training. High protein diets help to preserve muscle mass during weight loss. Mediterranean-style diets are associated with greater lean mass and lower adiposity, while Western-style diets are linked to higher adiposity and lower muscle mass. Changing what you eat and how you eat can drastically change body composition and how the body uses the energy it is fed.

Exercise

Low levels of activity are associated with lower muscle mass, greater adiposity and lower bone mass. All of these are linked to poor health outcomes. A more active lifestyle is associated with the opposite and is linked to greater healthspan and lifespan. Research has clearly shown that exercise is not optional if you want to work towards a healthier body composition and improve your quality of life.

Peptides That Promote Lower Adiposity

With the epidemic of obesity around the world, there has been a surge of interest in drugs that can promote weight loss. Although there have been many fad diets and drugs that have surged in popularity before fading into the background, none have been quite as effective as the Glucagon-Like Peptide-1 receptor agonists (GLP1RAs).

Since the development of semaglutide, other drugs that target additional receptors to provide even greater weight loss results have been developed. The target receptors for these drugs include:

• Glucagon-like peptide-1 receptor (GLP-1R): Activation of this receptor enhances insulin secretion, suppresses appetite, delays gastric emptying and exerts anti-inflammatory effects.
• Glucose-dependent insulinotropic polypeptide receptor (GIPR): Enhances insulin secretion in response to glucose, promotes lipogenesis, lipid oxidation, thermogenesis and energy expenditure and suppresses appetite.
• GCGR: Stimulates hepatic glucose production, gluconeogenesis and amino acid catabolism. It also enhances glucose disposal, to improve glucose tolerance and increases FGF21 levels, to promote lipid metabolism.

The drugs that we will be discussing in this article that target these receptors are all peptides that have been modified to bind to these receptors or a combination of these receptors to stimulate their activity.

• Peptides that target just one receptor include: Semaglutide, liraglutide, exenatide and dulaglutide.
• Dual receptor agonists include: Mazdutide and servodutide, both of which target GLP-1R and GCGR. Tirzepatide targets GLP-1R and GIPR.
• Triple receptor agonists include: Retatrutide, SAR441255 and xGLP/GCG/GIP-32.

The main feature of these peptides is that they aim to reduce body weight and help to control blood sugar levels. The hope is that they will alter body composition by reducing adiposity to a greater extent than other tissues.

Clinical Test/Trial Results

Since there are many of these drugs, we will look at some of the results of just a few of these peptides on people with and without type 2 diabetes (T2D) as reported by review papers.

• Semaglutide: At a dose of 2.4mg, patients lost an average of 11.53% body weight, while patients with T2D lost 6.2% body weight.
• Mazdutide: A dose of 6mg produced a reduction in body weight of 12.73% in obese patients, and 5.73% in patients with T2D.
• Tirzepatide: 15mg of tirzepatide caused a reduction in weight of 16.53% in those with obesity, and 10.66% in patients with T2D.
• Retatrutide: A dose of 12mg produced an impressive reduction in body weight by 22.10% in obese patients, and 13.78% in those with T2D¹⁵.

A review paper on 17 GLP1RAs found that in overweight non-diabetics, the strongest results were seen by retatrutide, followed by tirzepatide, semaglutide and lastly mazdutide. This paper also separated studies on Asian and Caucasian patients, which brought to light significant differences in the efficacy of these drugs on these groups. Asian patients appeared to respond more strongly to semaglutide than to tirzepatide and mazdutide. Retatrutide was not included in this particular comparison, so we do not know how it would perform for this particular group. To date, retatrutide has not been tested on a significant number of Asians¹⁶.

It is worth noting that when body weight is mentioned, it refers to total body weight and does not specify what proportion of each tissue type is lost. Not all studies look at the effect of these drugs on body composition.

Side Effects

These weight loss peptides come with similar side effects, the most common being:

• Nausea
• Vomiting
• Diarrhoea
• Constipation

They may also increase the risk of pancreatitis and are not recommended for people with a personal or family history of thyroid cancer¹⁷.

These drugs can influence body composition unfavourably to some extent. Not only do they reduce adiposity, but they can also promote the loss of muscle. This loss of muscle can put people at risk of other health problems, such as frailty and sarcopenia^18,19. Their effect on bone is varied, with some studies indicating that they may promote bone formation, and others finding evidence of increased bone resorption^20,21.

Approval Status

Semaglutide and tirzepatide are approved for the treatment of T2D and weight management.

Mazdutide is approved for the treatment of T2D and for weight management in China.

Retatrutide is a research chemical, not currently approved for the treatment of any disease.

Populations Who Benefit the Most

These drugs are so effective that it is easy to be tempted to use them as a quick fix for an unhealthy body composition, but it is important to note that most people who stop taking them regain weight, as the drugs do not help to implement healthy eating habits. Instead, they alter metabolism and behaviour towards food. This influence is lost upon ceasing the medication, as such, old habits can easily return.

They are still incredibly helpful for those who are struggling to lose weight and who are at high risk of disease due to their weight. But while these drugs are used, the people who are taking them must also take care to make sustainable changes to their diet and lifestyle, which they can maintain after they have reached their weight goals and come off the drug.

Since there is a combination of positive and negative changes that occur in body composition while on these weight loss peptides, whether or not to take them is something that should be carefully considered. Exercise signals to the body to keep and build muscle and bone, so exercise while on these weight loss peptides may help reduce the loss of these beneficial tissues^22,23.

Conclusion

By looking at a person’s body composition, we can understand a lot about their health and make some accurate predictions about their risk of developing disease. With the emergence of GLP1RAs, GIPRAs and GCGRAs, we have the ability to quickly and effectively alter body composition so that it leans more towards healthy percentages. Although weight loss peptides lead to a significant and rapid reduction in adiposity, they can also reduce muscle mass and, in some cases, bone mass. For this reason, these drugs should not be taken lightly. By adopting a healthy diet and lifestyle, not only is muscle and bone loss mitigated, but the development of these habits ensures that the benefits of weight loss will persist after the drug is no longer needed.

 

You can buy mazdutide and retatrutide for your research here.

 

References

1. De Lorenzo A, Bianchi A, Maroni P, et al. Adiposity rather than BMI determines metabolic risk. Int J Cardiol. 2013;166(1):111-117. doi:10.1016/j.ijcard.2011.10.006
2. Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008;88(4):1379-1406. doi:10.1152/physrev.90100.2007
3. Bao JF, She QY, Hu PP, Jia N, Li A. Irisin, a fascinating field in our times. Trends Endocrinol Metab TEM. 2022;33(9):601-613. doi:10.1016/j.tem.2022.06.003
4. Arrieta H, Hervás G, Rezola-Pardo C, et al. Serum Myostatin Levels Are Higher in Fitter, More Active, and Non-Frail Long-Term Nursing Home Residents and Increase after a Physical Exercise Intervention. Gerontology. 2018;65(3):229-239. doi:10.1159/000494137
5. Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8(8):457-465. doi:10.1038/nrendo.2012.49
6. Iglesias P. Muscle in Endocrinology: From Skeletal Muscle Hormone Regulation to Myokine Secretion and Its Implications in Endocrine-Metabolic Diseases. J Clin Med. 2025;14(13):4490. doi:10.3390/jcm14134490
7. Obradovic M, Sudar-Milovanovic E, Soskic S, et al. Leptin and Obesity: Role and Clinical Implication. Front Endocrinol. 2021;12:585887. doi:10.3389/fendo.2021.585887
8. Fang H, Judd RL. Adiponectin Regulation and Function. Compr Physiol. 2018;8(3):1031-1063. doi:10.1002/cphy.c170046
9. Sudan SK, Deshmukh SK, Poosarla T, et al. Resistin: An inflammatory cytokine with multi-faceted roles in cancer. Biochim Biophys Acta Rev Cancer. 2020;1874(2):188419. doi:10.1016/j.bbcan.2020.188419
10. Guerre-Millo M. Adipose tissue hormones. J Endocrinol Invest. 2002;25(10):855-861. doi:10.1007/BF03344048
11. Karsenty G. Osteocalcin: A Multifaceted Bone-Derived Hormone. Annu Rev Nutr. 2023;43:55-71. doi:10.1146/annurev-nutr-061121-091348
12. Agoro R, White KE. Regulation of FGF23 production and phosphate metabolism by bone-kidney interactions. Nat Rev Nephrol. 2023;19(3):185-193. doi:10.1038/s41581-022-00665-x
13. Oniszczuk A, Kaczmarek A, Kaczmarek M, et al. Sclerostin as a biomarker of physical exercise in osteoporosis: A narrative review. Front Endocrinol. 2022;13:954895. doi:10.3389/fendo.2022.954895
14. Mosialou I, Shikhel S, Liu JM, et al. MC4R-dependent suppression of appetite by bone-derived lipocalin 2. Nature. 2017;543(7645):385-390. doi:10.1038/nature21697
15. Xie Z, Zheng G, Liang Z, Li M, Deng W, Cao W. Seven glucagon-like peptide-1 receptor agonists and polyagonists for weight loss in patients with obesity or overweight: an updated systematic review and network meta-analysis of randomized controlled trials. Metab – Clin Exp. 2024;161. doi:10.1016/j.metabol.2024.156038
16. Zhang S, Yu B, Xu J, et al. Quantitative Comparison of Glucagon-Like Peptide-1 Receptor Agonists on Weight Loss in Adults: A Systematic Review and Model-Based Meta-Analysis. Diabetes Technol Ther. 2025;27(6):422-429. doi:10.1089/dia.2024.0533
17. Drucker DJ. Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity. Diabetes Care. 2024;47(11):1873-1888. doi:10.2337/dci24-0003
18. Sr DCC. Health, risks and disease in therapeutic functionalities of Glucagon-like peptide-1 receptoragonists (GLP-1RAs) concerning human susceptibility. Greenfort Int J Appl Med Sci. 2025;3(5):240-254. doi:10.62046/gijams.2025.v03i05.002
19. Beavers KM, Cortes TM, Foy CM, et al. GLP1Ra-based therapies and DXA-acquired musculoskeletal health outcomes: a focused meta-analysis of placebo-controlled trials. Obesity. 2025;33(2):225-237. doi:10.1002/oby.24172
20. Karam L, Mabilleau G, Paccou J. Effects of Glucagon-Like Peptide-1 receptor agonists on bone health in people living with obesity. Osteoporos Int. 2025;36(11):2115-2126. doi:10.1007/s00198-025-07664-1
21. Pereira M, Jeyabalan J, Jørgensen CS, et al. Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice. Bone. 2015;81:459-467. doi:10.1016/j.bone.2015.08.006
22. Memel Z, Gold SL, Pearlman M, Muratore A, Martindale R. Impact of GLP- 1 Receptor Agonist Therapy in Patients High Risk for Sarcopenia. Curr Nutr Rep. 2025;14(1):63. doi:10.1007/s13668-025-00649-w
23. Jensen SBK, Sørensen V, Sandsdal RM, et al. Bone Health After Exercise Alone, GLP-1 Receptor Agonist Treatment, or Combination Treatment: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024;7(6):e2416775. doi:10.1001/jamanetworkopen.2024.16775