For decades, weight-loss aisles have been packed with thermogenic fat burners promising to “ignite metabolism” and “incinerate fat.” However, these quick-fix supplements often fall short of delivering lasting results.
Today, the pharmaceutical landscape is shifting. Emerging treatments like GLP-1 agonists (Glucagon-like peptide-1) are redefining how we approach metabolic health, offering a scientifically-backed path to long-term weight loss sustainability.
Unlike traditional stimulants, these new weight-loss medications work with your body’s natural chemistry to regulate appetite and blood sugar. If you’ve been searching for a more effective alternative to over-the-counter supplements, understanding the science behind GLP-1 could be your first step toward a healthier future
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The GLP-1 Origin Story
GLP-1 drugs were initially developed for type 2 diabetes treatment due to their ability to regulate blood sugar1.
In the early 1990s, Dr John Eng discovered a hormone in the venom of the Gila monster (a lizard native to the US Southwest) that regulated blood sugar. This led to the first GLP-1 drug (exenatide).
Originally designed strictly to manage type-2 diabetes by stimulating insulin production, in a fortunate coincidence, researchers noticed a consistent “side effect” in clinical trials: patients lost significant weight, as the drug also regulates appetite and slows digestion.
The drugs were effectively treating obesity by fixing a hormonal imbalance, proving that weight is often a biological issue, not just an issue related to willpower. Based on this discovery, GLP-1 agonists were further developed and approved specifically as weight loss medications for obesity.
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Global Phenomenon
With about 3 billion people globally who are overweight or obese, according to data from the World Obesity Federation, anything that can help stem the tide can have a hugely beneficial impact.
People are also looking for more effective ways to lose weight and keep it off, because most people who lose weight often regain a significant portion within 1 to 3 years. For example, within one year, the majority of people regain about two-thirds of the lost weight.
Long-term success is challenging, with a meta-analysis2 showing that after five years, more than 80% of lost weight is regained.
Unsurprisingly, medications for weight loss have skyrocketed in popularity over the last few years – a 2025 KFF Health Tracking Poll found that about one in five adults in the US have already taken GLP-1 medication, and one in eight continue to use them.
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Flip the Hunger Switch
These medications work primarily by mimicking the natural hormone glucagon-like peptide-1, which is naturally produced in the gut, regulating appetite, increasing feelings of fullness and reducing hunger, which is what leads to the weight loss1.
Delayed gastric emptying is the most immediate physical effect you experience when taking these medications. Under normal conditions, when you eat a meal, your stomach contracts to push food into your small intestine fairly quickly, often within 2 to 4 hours.
GLP-1 medications act like a traffic controller, putting up a stop sign. They significantly slow down the motility of the stomach. That means food stays in your stomach for much longer, so you physically feel full after eating.
Slowing your digestion in this way also means that a portion that is half the size of what you normally eat can make you feel satiated. If you try to overeat, the physical pressure in your stomach sends a distress signal, like nausea, forcing you to stop eating.
In addition, GLP-1 agonists bind to receptors in the region of the brain that regulates your energy balance, called the hypothalamus (specifically the arcuate nucleus). They chemically mimic the signal of satiety (fullness) that usually only comes after a massive meal.
In people who are obese, this regulatory mechanism often gets stuck at a higher weight. When you diet, the hypothalamus panics, thinking you are starving, and floods you with hunger hormones to get you back to your set point.
However, GLP-1 medication convinces your hypothalamus that you have plenty of energy stored, so it stops sending these powerful hunger signals.
Dampens Dopamine
In what scientists are now calling the most revolutionary aspect of these drugs, GLP-1 agonists also work at the hormonal level to suppress emotionally driven hunger.
The reality is that we don’t just eat for energy; we also eat to get a dopamine hit, especially from sugar and fat. This is the pleasure-impulse loop known as hedonic hunger — those cravings for cake, chocolate or ice-cream when you are sad or tired.
As GLP-1 receptors are also found in the parts of the brain that light up when we see sugar, fat, or alcohol, the medication dampens the dopamine hit you get from high-calorie food. It turns the volume down on the reward. This benefit is known as hedonic de-escalation.
By working on the brain and the digestive system, the rise of GLP-1 weight-loss medication represents a move away from the “furnace” model of weight loss.
The effect that GLP-1 has on the reward centres of the brain is also showing promise in treating addiction, opening new avenues for applications in food addiction, as well as potential applications in treating drug and alcohol addiction2.
Output versus Input
Where thermogenic fat burners tried to outrun excess calories by boosting your metabolism to elevate energy output – a battle that is mathematically very difficult to win (a thermogenic might burn an extra 50–100 calories a day, roughly the amount in half a cookie) – GLP-1s address the input.
By silencing the hunger signals that drive overeating, these medications allow the body to naturally enter a calorie deficit without the white-knuckled struggle of willpower, dieting and excess exercise. However, that doesn’t mean you don’t need to eat well and exercise when taking GLP-1 medications.
These medications are typically prescribed alongside lifestyle changes like diet and exercise for the best outcomes.
Important Considerations
While GLP-1 medications are proving highly effective at helping users treat obesity, this weight loss is indiscriminate.
Studies3 show that those taking these medications lose muscle and fat, which makes it essential that diets contain sufficient protein with every meal, augmented with protein supplements, especially around training.
Anyone taking GLP-1 medications should aim for:
- 20-30g of protein at every meal from foods like fish, chicken, beans, chickpeas, or tofu.
- At least 1.6g of protein per kg of body weight daily if moderately active, and up to 2.2g/kg/day if you train hard.
- Healthy fats like avocado or olive oil, which are essential for keeping you satisfied and keeping your energy stable.
Combining a higher protein intake with weight training is a great way to maintain and even build muscle while taking these medications.
It is also important to take a more intentional approach to fuelling your body effectively when taking these medications because they suppress your appetite. The reduced energy intake can impact highly active individuals who would require a premium fuelling strategy for each meal.
To maintain energy for your workouts and avoid blood sugar crashes, shift toward grazing on nutrient-dense, smaller meals punctuated by snacks like fruit, nuts, or unsweetened yoghurt.
When you do sit down to eat, prioritise slow-burning natural complex carbohydrates (like whole grains like rolled oats, millet, quinoa, brown rice, and sweet potatoes) over refined grains or sugary drinks.
This metabolic shift also requires a different approach to your eating schedule. The very mechanism that helps you lose weight – slowed gastric emptying – can trigger nausea if you eat too much or don’t space meals far enough apart.
To bypass the queasiness, steer clear of high-fat, fried foods or processed meats, which sit heavy in the stomach. Instead, opt for baking or steaming your proteins and lean on bland staples like whole-grain toast, crackers, or ginger tea if you feel unsettled.
Heartburn is another common issue reported by GLP-1 users. This is often caused by lying down too soon after eating or consuming foods like chili, garlic, and black pepper. The fix is often mechanical: keep your portions small and stay upright for at least two to three hours after a meal to let gravity do the work.
Finally, a critical and often overlooked element when taking GLP-1 is hydration and its impact on digestive regularity. The medication can blunt your thirst signals, leading to dehydration that exacerbates both nausea and constipation.
Aim for two to three litres of liquid daily, prioritising water and water-rich foods like cucumbers, watermelon, and soups while minimising alcohol and caffeine. If things slow down too much, address the issue with a combination of soluble fibre (oats, apples), insoluble fibre (vegetable skins, nuts), and plenty of water to keep your system moving.
Extreme calorie restriction can also worsen dehydration and may lead to fatigue, kidney problems, and nutrient deficiencies that lead to excessive and unhealthy weight loss.
Beware Fake Products
Due to the popularity of these medications, a large and thriving black market has emerged where knock-offs are sold to the public, commonly through social media platforms.
The South African Health Products Regulatory Authority (SAHPRA) recently issued a warning to consumers, cautioning against the purchase and use of unregistered and unsafe versions of these medications.
SAHPRA has also become aware of companies and individuals illegally marketing GLP-1 products online, and falsely claiming to be affiliated with or authorised by SAHPRA and some of South Africa’s major retail pharmacies.
The Next Frontier
The current wave of GLP-1 drugs represents the next evolution for obesity treatment and weight loss. We are witnessing the end of the “willpower” era and the beginning of the “biological” era of weight loss.
These medicines suggest that we will soon manage obesity exactly like hypertension or asthma: a chronic condition with highly effective, non-judgmental medical solutions.
References:
- Collins L, Costello RA. Glucagon-Like Peptide-1 Receptor Agonists. [Updated 2024 Feb 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551568/.
- Hall KD, Kahan S. Maintenance of Lost Weight and Long-Term Management of Obesity. Med Clin North Am. 2018 Jan;102(1):183-197. doi: 10.1016/j.mcna.2017.08.012. PMID: 29156185; PMCID: PMC5764193.
- Klausen MK, Thomsen M, Wortwein G, Fink-Jensen A. The role of glucagon-like peptide 1 (GLP-1) in addictive disorders. Br J Pharmacol. 2022 Feb;179(4):625-641. doi: 10.1111/bph.15677. PMID: 34532853; PMCID: PMC8820218.
- Mehrtash F, Dushay J, Manson JE. I Am Taking a GLP-1 Weight-Loss Medication—What Should I Know? JAMA Intern Med.2025;185(9):1180. doi:10.1001/jamainternmed.2025.1133.
Author: Pedro van Gaalen
When he’s not writing about sport or health and fitness, Pedro is probably out training for his next marathon or ultra-marathon. He’s worked as a fitness professional and as a marketing and comms expert. He now combines his passions in his role as managing editor at Fitness magazine.
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