Peptides For Weight Loss: How Do Weight Loss Pills Work?

Peptides are at the centre of innovative weight management solutions. These short sequences of amino acids have garnered attention for their role in regulating appetite, metabolism, and body weight. This article examines the scientific support for specific peptides in weight loss and discusses their potential risks.
Klara Hatinova

Klara Hatinova

Klara is postgraduate researcher in experimental psychology at the
University of Oxford.

A blue image with text saying "Peptides in Weight Loss: Decoding Their Role and Impact Loss"

Understanding Peptides: Building Blocks of Proteins

Understanding what peptides are is critical to evaluating how peptides work to support weight loss.

Peptides are short chains of amino acids, typically between 2 and 50 amino acids, linked together by peptide bonds. They are the building blocks of proteins—peptides can configure together through more elaborate bonds into a 3D protein [1, 2]. Peptides have a wide range of biological functions, can penetrate cell membranes, and are resistant to degradation, making them potential therapies and weight loss interventions [3].

Most importantly, peptides are the building blocks of the human body and are essential for healing and repair. Common examples of endogenous peptides include hormones such as insulin, ghrelin, and leptin, which are relevant to weight loss but also immune-supporting peptides and neurotransmitters for brain health.

Outside of medical use, peptides are also widely used in the food and skincare industry and can be derived from biological sources or manufactured in the lab [4].

In the pharmaceutical industry, peptides are used as antioxidants, antihypertensive, anticoagulant, and immunomodulatory compounds, among other functions. Peptides can regulate endocrine, nervous, and immune system functions and gene expression [5]. This is because peptides can be formulated to overcome some barriers, including the blood-brain barrier or pathogen membranes [6]. Peptide-based drugs are considered safer, as their breakdown generates amino acids, which can be utilized by the body [7].

Harnessing Your Body’s Peptides for Weight Loss

Peptides are the essential hormones that signal satiety, initiate fat storage, regulate blood sugar and promote cravings. There are five essential peptides relevant to weight loss and gut health, although several additional peptides have been less studied.

GLP-1: A Natural Appetite Regulator for Weight Control

GLP-1 is a peptide released from the L-cells in the small intestine that increases satiety and reduces food-seeking behaviour. It can do this one of two ways [8]:

  • Activating the Vagus Nerve, which would carry the electrical signal along its branch into the brain
  • Travelling through the blood into the brain, crossing the blood-brain barrier, and binding to receptors in the hypothalamus (as well as the hippocampus, nucleus accumbens and ventral tegmental area)

GLP-1 induces satiety by acting on a spectrum of midbrain and hindbrain regions and stimulates insulin release, effectively regulating weight and blood sugar.

Insulin: The Sugar Regulator’s Role in Weight Management

Insulin is a well-known hormone released from the pancreas into the blood in response to sugar in the diet. It acts on cells throughout the body to stimulate and then take up glucose from the blood, reducing blood sugar. Reducing blood sugar too much can be caused by excess insulin, such as after eating high-sugar food. This drop in blood sugar can make you hungry again. Therefore, too much insulin can interfere with weight loss [9].

Insulin is nonetheless critical for keeping blood sugar stable and synthesizing new proteins, such as muscle tissue. Therefore, keeping a responsive level of insulin, which can act when you consume high-sugar foods, is necessary for weight loss.

Leptin: Deciphering the Signals of Satiety and Fat Storage

Leptin is a signal of adiposity. Simply put, leptin tells your brain how much fat you have stored so the brain can decide whether it needs more or less fat. Therefore, leptin is a long-term regulator of hunger and satiety [10].

Leptin is released from fat cells, which means the higher your leptin will be the more fat cells you have. Leptin is why people who lose weight feel hungrier – they have just lost much of their leptin.

Nonetheless, the role of leptin in the body goes beyond just signalling adiposity. It is also vital for adaptation to starvation, reproductive function and the ‘fight-or-flight’ response, so simply supplementing more leptin is not a good idea [11].

Ghrelin: The Double-Edged Sword of Hunger and Weight Loss

Ghrelin is a peptide that signals hunger, often felt by the stomach's growling. Ghrelin peptide is released from the stomach and starts up your digestive system in preparation for getting food [12]. Ghrelin, therefore, significantly increases food intake.

Moreover, ghrelin can increase the tendency to store fat and reduce the energy you expend at rest [13]. Ghrelin is, therefore, the peptide goblin of weight loss.

Neuropeptide Y: The Stress-Induced Appetite Booster

Neuropeptide Y (NPY) is a peptide that acts with Ghrelin to promote food intake when low energy stores. NPY is likely responsible for craving high-carbohydrate foods when hungry [14]. Similarly to ghrelin, NPY increases the tendency to store fat.

Distinct to ghrelin, NPY is released from the sympathetic nervous system – the peripheral nervous system active under stress. This means that your levels of NPY are elevated under stress. Does stress snacking sound familiar? This is probably your brain being flooded by NPY [15].

Innovative Peptide Drugs: A New Horizon in Weight Loss Treatment

Yes, peptide-based drugs can and are used for weight loss.

The two most prominent peptide drugs for weight loss are liraglutide and Semaglutide.

Liraglutide: Imitating Nature to Curb Appetite

Liraglutide is a peptide that is 97% similar to GLP-1 and, therefore, mimics the natural function of GLP-1 to reduce appetite and stabilize blood sugar. It stays in the body for about 13 hours and can be injected 1x a day [16].

Liraglutide, marketed by Novo Nordisk, increased weight loss by about 5kg compared to placebo over 56 weeks when administered alongside exercise and a calorie deficit [17].

Semaglutide: The Weight Loss Breakthrough

Semaglutide is a newer peptide for weight loss, although it is very similar to liraglutide. Like liraglutide, semaglutide mimics the role of GLP-1 in the body and is marketed by Novo Nordisk.

Semaglutide significantly impacts weight—over 68 weeks, patients who received semaglutide once a week lost 14.9% of their weight compared to 2.4% in the placebo group [17, 18]. Therefore, semaglutide is an economically more effective peptide for weight loss [17, 19].

Differentiating Semaglutide Formulations: Wegovy, Ozempic, and Rybelsus

Wegovy, Ozempic or Rybelsus are all different doses formulated around semaglutide. Wegovy and Ozempic are both injectable, whereas Rybelsus comes in 7 and 14-mg tablets [20].

All of these formulations are novel additions to the pharmaceutical company's diabetes management portfolio. Ozempic was first approved in 2017, and Wegovy followed only recently in 2021. Wegovy has additionally been approved for weight loss management at a dose of 2.4mg/day, which the patients themselves can inject.

Ozempic had a more prominent media campaign and is therefore mistakenly also considered to have FDA approval for weight loss. This is not true – Ozempic is primarily a peptide used for diabetes but can be prescribed off-label for weight loss.

It's important to note that although peptides can aid in weight loss, they are not a standalone solution. Factors such as diet, exercise habits, personal health history, and an individual's specific reaction to peptide drugs also play a significant role [21].

Side Effects of Taking Peptides for Weight Loss

Peptides for weight loss, particularly GLP-1 receptor agonists, can have severe side effects, which is why they are only approved for use in individuals whose weight poses a greater risk than the side effects of the drug. One of the most common side effects is gastrointestinal issues. These can include nausea, vomiting, diarrhoea, and stomach upset, ranging from mild to moderate in severity [22, 23].

Another side effect reported is an increased heart rate, which can lead to dizziness and headaches.

A misnomer side effect of peptides for weight loss is facial ageing, also called ‘Ozempic face’. This is a physical symptom where the skin on your face becomes loose and saggy [24]. This, however, isn’t caused by the peptide but rather by the rapid reduction of weight from the face area.

Therefore, the side effects of taking peptides for weight loss, compounded by rapid weight loss, should be weighed against the benefits of losing weight. Consulting your healthcare provider is a critical step to take before considering peptide drugs for weight loss.

Summary: The Role of Peptides for Weight Loss

As obesity continues to be a global health challenge, the role of peptides in weight loss becomes transformative and economically attractive. While promising, peptide therapy should be considered a component of a broader weight management strategy, which includes lifestyle changes and medical supervision. Understanding the science behind peptides can empower individuals and healthcare professionals to make informed decisions about their use in weight loss. Regulating natural peptides should be a first-line strategy to regulate satiety and support weight loss.

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Klara Hatinova

Klara Hatinova

Klara is a postgraduate researcher in experimental psychology at the University of Oxford. She has worked across a spectrum of hot topics in neuroscience, including her current project measuring reinforcement learning strategies in Parkinson’s disease. Previously, she studied the efficacy of psilocybin as a therapy for critical mental health conditions and examined molecular circadian rhythms of migraine disorders. She completed her undergraduate degree in Neuroscience at the University of Glasgow and participated in a year abroad at the University of California, where she worked on a clinical trial for spinal cord injury.