GLP-1 Drugs: Miracle or Misfire? Rethinking Weight Loss, Cravings, and Natural Hacks

Picking up from the previous blog, where we explored the powerful role of GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide)—two incretin hormones that regulate blood sugar, satiety, and insulin sensitivity. We saw how these ancient signalling molecules were evolutionarily designed to help humans survive food scarcity, responding strategically to nutrient intake by slowing digestion, curbing appetite, and fine-tuning metabolism.

But that finely tuned system wasn’t built for our modern environment—an environment overloaded with ultra-processed foods that hijack hunger cues, overwhelm the gut-brain axis, and disrupt hormonal feedback loops. Instead of rare and meaningful signals triggered by whole foods, our bodies now face a constant stream of empty stimuli, blunting the response of GLP-1 and GIP and contributing to metabolic dysfunction, weight gain, and insulin resistance.

In this follow-up, we turn our attention to the rise of GLP-1 medications like Ozempic, Wegovy and Mounjaro—heralded as weight-loss miracles, but not without controversy. We'll explore:

• The problem with GLP-1 medications: What are the risks, side effects, and long-term implications of medicating a system that's already under strain?

• A smarter way to use GLP-1 drugs: Could these medications be better used to target specific vulnerabilities—like carb cravings—rather than as blunt tools for appetite suppression?

• Natural hacks to boost GLP-1: From dietary tweaks to lifestyle interventions, can we mimic the benefits of GLP-1 medications without the downsides?

Let’s unpack the hype, challenge the narrative, and explore a more sustainable path to metabolic health.

The Problem with Current GLP-1/GIP Use

The widespread adoption of GLP-1 medications like semaglutide has been met with fanfare. Weight loss clinics are booming, pharma stocks are surging, and social media feeds are filled with “before and after” photos. But behind this rapid rise lies a growing list of concerns—ones that deserve closer scrutiny, especially as these drugs are increasingly used at high doses and for prolonged periods.

Mental Health Risks: Depression, Anxiety, and Suicidal Thoughts

A major red flag emerged in late 2024 with a large-scale cohort study published in Scientific Reports, which examined over 160,000 matched patients—those using GLP-1 drugs versus those not. The findings were sobering. Psychiatric disorders jumped 98% in the medicated group, with major depression up 195%, anxiety up 108%, and suicidal behaviour up 106%.

This wasn't a clinical trial; it was real-world data, covering nearly a decade (2015–2023). While correlation doesn’t prove causation, it’s hard to ignore the weight of these numbers—especially when correlational data is routinely used to shape public health policy. These medications may be shrinking waistlines, but are they also dulling minds? This is particularly concerning given the mental health crisis many communities are already navigating.

A deeper question arises: could the mechanism that blunts cravings for junk food also be muting pleasure and motivation in general? When a patient no longer feels compelled to binge on sweets, could they also lose interest in things they once loved—like sports, social activities, or hobbies? If that’s the case, it could explain some of the psychological toll these drugs may carry.

Indeed, we already see evidence that GLP-1 analogues reduce reward sensitivity more broadly. One oft-cited “benefit” is reduced alcohol consumption in users of semaglutide and other GLP-1 agonists. That may sound like a win at first—especially in the context of addiction. But when you zoom out, it’s not so clear-cut. These drugs appear to function somewhat like naltrexone, a medication that blunts the brain’s reward response by targeting opioid receptors. Naltrexone can help reduce addictive behaviours—but it comes with a catch: blunted reward often leads to blunted emotional experience. The desire for destructive behaviour may fade—but so too might the desire to engage in meaningful or joyful activities.

In practice, suppressing the amplitude of the reward signal might look good on paper, but it doesn’t always play out so cleanly. We’re not just dampening cravings—we may be dampening the desire to live. That’s not hyperbole. Major depressive disorder has now been reported in increasing numbers among patients on Ozempic and similar drugs.

When reward pathways are globally muted, the human drive for connection, achievement, and pleasure can go with it.

This brings to mind a cautionary tale from the early 2000s: Rimonabant. Once hailed as a breakthrough treatment for obesity and smoking cessation, Rimonabant worked by blocking the brain’s cannabinoid CB1 receptors, essentially turning down the activity of the endocannabinoid system. This system plays a key role in modulating appetite, mood, emotion, pain, and reward. By antagonising CB1 receptors, Rimonabant effectively reduced food intake and helped improve metabolic markers—but at a cost.

Here’s why: the endocannabinoid system also regulates mood and emotional resilience. Inhibiting CB1 receptors centrally, especially in areas like the prefrontal cortex and limbic system, can reduce dopamine release and interfere with serotonin signalling. The result? Users experienced a marked increase in depression, anxiety, irritability, and suicidal ideation. These effects were so pronounced that, despite its metabolic benefits, Rimonabant was withdrawn from the market due to safety concerns.

GLP-1 drugs, while not directly targeting the endocannabinoid system, may be tapping into overlapping neurochemical territory. GLP-1 receptors are expressed in the brain’s reward centres—like the hypothalamus and nucleus accumbens—and modulate dopamine-driven behaviours. If this modulation becomes too broad or too blunt, there’s a risk of not just suppressing food cravings, but also flattening the emotional tone of daily life. Much like Rimonabant, GLP-1 drugs may offer short-term metabolic wins while quietly chipping away at mental wellbeing—especially if used at high doses or in vulnerable populations.

These concerns aren’t about demonising GLP-1 medications, but about grounding the conversation in the full scope of what these powerful tools actually do. Weight loss at the expense of mental health is not a win—it’s a trade-off that deserves more transparency and better targeting.

Digestive Risks: GLP-1 Drugs and Gastroparesis

GLP-1 medications slow gastric emptying to help control appetite—but sometimes, they slow it too much. A study in Gastroenterology linked high-dose semaglutide to gastroparesis, a condition where the stomach's motility grinds to a near halt. This can lead to severe bloating, nausea, constipation, and even life-threatening complications in extreme cases.

Digestion is not a system we can afford to destabilise lightly. Gut motility affects nutrient absorption, microbiome balance, and systemic inflammation. Interfering with it, even in pursuit of weight loss, can have wide-ranging unintended effects.

Muscle Loss and the Risk of Frailty

Another under-discussed consequence is the significant loss of lean mass. In the STEP-1 trial, published in The New England Journal of Medicine (2021), up to 40% of the weight lost on semaglutide was from lean mass—including muscle and connective tissue.

This matters. Muscle isn’t just about strength or aesthetics; it’s a metabolic powerhouse, helping the body regulate blood sugar and maintain insulin sensitivity. It’s also one of our best defences against ageing and frailty. Strip away too much of it, and we risk trading short-term weight loss for long-term metabolic vulnerability.

Diminishing Returns: When the Drug Stops Working

Even when GLP-1 drugs seem effective initially, their benefits may fade with time. The STEP-5 trial, published in Nature Medicine (2022), tracked participants over two years. By the end of the study, hunger and cravings had returned to pre-treatment levels—even though participants were still on the drug. About one-third of the lost weight was regained.

The body appears to adapt, making the early results difficult to sustain. If long-term use leads to diminishing returns, it raises difficult questions about dependency, dosage escalation, and the sustainability of this approach.

Image Credit: Healthline

A Smarter Way to Use GLP-1 Drugs: Targeting Carb Cravings

Most people aren’t dreaming of steak or boiled eggs when a craving hits. Let’s be honest — cravings are almost always for the sweet, the gooey, the crunchy, the salty. And what’s the common denominator? Refined carbohydrates. No one’s begging for a stick of butter during movie night.

This is where GLP-1 drugs show real promise — not as general appetite suppressants but as targeted tools to break the cycle of carb addiction. A 2016 study in Appetite found that liraglutide, an early GLP-1 drug, reduced cravings for sweets and starches more than other types of food. It did this by altering brain activity in reward and appetite centres, giving users a better shot at resisting carb-driven urges.

That should be the focus — not necessarily maximising weight loss, but regaining control over carbohydrate cravings. And to do that safely and effectively, here’s a practical, evidence-based strategy:

Step 1: Use the Lowest Effective Dose

Start low. Work with your clinician to find the minimal effective dose — not the maximum. This might be just 0.25 mg of semaglutide weekly instead of the common 2.4 mg dose. That’s a tenth of the standard dose.

The goal isn’t to suppress all hunger. That blunts quality of life. The goal is to restore control — especially over processed carbs and sugars. You don’t want to remove all desire to eat, just to tame the monster.

Step 2: Preserve Muscle with Resistance Training

Rapid weight loss comes at a cost — often in the form of lean mass, which includes muscle. Resistance training can counter this. Whether it’s weights, bodyweight exercises, or resistance bands, aim for three to four sessions per week.

A study in Medicine & Science in Sports & Exercise showed that resistance training preserves lean mass even when weight is lost through calorie restriction. While the study didn’t focus on GLP-1 drugs, the principle stands: preserving muscle maintains metabolic rate and protects against frailty as you age.

Step 3: Rethink Your Plate — Low Carb, Protein-Focused

Want to make GLP-1 therapy even more effective? Reinforce it with a diet that helps stabilise hunger hormones and blood sugar. Prioritise protein (e.g. eggs, steak, yoghurt) and healthy fats. Avoid refined carbs like bread, pasta, or sweets.

A study in the American Journal of Clinical Nutrition found that low-carb diets outperformed others for weight loss and metabolic improvements — especially in people with insulin resistance. Since most people who seek GLP-1 therapy are likely insulin resistant to begin with, this is a powerful synergy.

GLP-1 drugs can make low-carb eating more sustainable by dulling the intense drive to consume sugar and starch. That’s the behavioural window worth capitalising on.

Step 4: Cycle Off the Drug After 3–6 Months

This isn’t meant to be a forever medication. After three to six months — again, under the guidance of your doctor — consider tapering off. Use that period to test yourself. Have the cravings for processed carbs quieted down? Can you walk past the bakery without hearing it call your name?

If yes, fantastic. You’ve built new habits. If no, a short reintroduction might be useful — but always with the long-term goal of independence, not lifelong dependence. GLP-1 drugs, when used wisely, can be a training tool — like stabilisers on a bike. But eventually, you want to ride on your own.

Image Credit: GT Health

Using GLP-1 Medications Wisely

So here’s the takeaway: lift weights, keep processed carbs low, and cycle off the drug to see what sticks after a few months. Learn — truly learn — what it feels like to eat in a way where carbohydrates aren’t dominating your plate, or your mind.

Quick fixes are seductive. And GLP-1 drugs do deliver — at least in the short term. But improving metabolic health is not a sprint. It’s a long game. The risks are real: muscle loss, emotional flattening, digestive issues, and depressive symptoms. That’s not a victory if, in ten years, you’re metabolically worse off, not better.

This four-part strategy — using a low dose, protecting muscle through resistance training, eating a low-carb, protein-rich diet, and cycling off the drug — gives you the benefits without the fallout. It helps you target cravings at the root and build habits that will last beyond the syringe.

It’s not flashy. But it’s grounded in physiology, behaviour change, and what long-term studies are starting to show.

And yes — a common question is: “Why not just stay on the drug indefinitely?” Hopefully, that’s clearer now. Beyond the financial cost, which is significant, the Step 5 trial showed weight tends to creep back on. But the weight coming back isn’t muscle or bone — that rarely rebounds. It’s body fat. You may look slightly slimmer, but be proportionally fatter than when you started.

Others ask, “What if I hate lifting weights?” That’s okay. The best exercise is the one you’ll do. Just focus on tiring your muscles. Squat up from a chair. Do push-ups on your knees. Walk with resistance bands. Fatiguing muscle tissue is what matters — not gym memberships or heavy barbells.

And no, not all carbs are bad. But be selective. If your carbs come in a bag, a box, and have a barcode — be cautious. Prioritise whole vegetables and fruits. Eat them, don’t drink them. Scrutinise how each food affects your mental clarity and craving cycles. Broccoli isn’t feeding your addiction. A frosted doughnut is.

Natural Ways to Boost GLP-1

There are several natural methods that can help boost GLP-1 production. Let's explore some of them:

Yerba Mate

Research from Dr. Ben Bikman's (from who this blog is inspired from) lab at BYU has shown that yerba mate, the traditional herbal tea, significantly increases GLP-1 levels, with an increase of about 40 to 50%. The compound focused in this study was ferulic acid, which modestly stimulated GLP-1 production. However, its microbial metabolite, dihydroferulic acid, caused a remarkable four-fold increase in GLP-1 levels when incubated with L cells. Drinking yerba mate regularly could be a practical way to increase GLP-1 and support metabolic health.

Additionally, yerba mate contains bitter tastants, which are molecules that promote satiety and reduce sweet cravings. These compounds stimulate taste receptors in the mouth and gut, enhancing the GLP-1 response while also helping control cravings.

Allulose

Another natural way to boost GLP-1 is through allulose, a rare sugar that does not spike blood glucose or insulin. Studies from Dr. Bickman's lab have shown that allulose increases GLP-1 levels significantly and rapidly, offering potential benefits for appetite suppression and blood glucose regulation.

Low-Ultra Processed Diet

Studies have demonstrated that a low-ultra processed diet, particularly one focusing on whole, minimally processed foods, can naturally increase GLP-1 secretion. This approach prioritises protein and healthy fats while reducing the intake of ultra-processed carbs, which can suppress GLP-1 production. By focusing on whole foods like vegetables, fruits, and lean proteins, you support GLP-1 secretion and help manage cravings.

Collagen Peptides

Collagen peptides have been shown to stimulate GLP-1 production and improve blood glucose control and insulin sensitivity. While collagen is often discussed for its benefits to skin and joint health, its metabolic benefits, particularly its ability to enhance GLP-1 secretion, should not be overlooked. High-protein meals, especially those including lean meats, eggs, and dairy, can also stimulate GLP-1 release more effectively than carbohydrates. Protein promotes satiety not only through GLP-1 but also by enhancing other hunger-regulating hormones like PYY.

Sleep

Quality sleep and maintaining a regular circadian rhythm are important for optimal GLP-1 function. Poor sleep has been linked to impaired GLP-1 responses and increased hunger. When you don't get enough sleep, your GLP-1 levels are blunted, leading to greater hunger and increased cravings the next day. Sleep disturbances, especially those that cause elevated blood glucose or a hyperglycemic state, can further disrupt your metabolism and sleep cycle, creating a vicious cycle of hunger and poor sleep.

Lemon Extract (Eriomin)

Scientists have found that eriocitrin, an antioxidant in lemons, can encourage L cells to produce more GLP-1. However, you would need to consume large amounts of lemon juice to get a significant effect. Thankfully, a concentrated extract called Eriomin has been developed. Eriomin has been clinically proven to increase GLP-1 by up to 17% after three months of use, offering a more convenient way to harness the power of lemon for GLP-1 production.

Apple Cider Vinegar

Apple cider vinegar has long been celebrated for its potential health benefits. It has also been shown to stimulate GLP-1 secretion, helping with appetite control and glucose metabolism. Including apple cider vinegar in your diet can be a simple yet effective way to support GLP-1 production naturally.

Eat your food in the right order 

Start with veggies, then protein and fats, and leave starches and sugars for last. This tactic not only supports GLP-1 production but also helps decrease post-meal glucose spikes.

Chew your food thoroughly

Mindful, slow chewing activates digestive processes that stimulate GLP-1 release. Studies show that solid foods lead to higher GLP-1 responses compared to pureed or liquid meals, prolonging satiety and supporting better appetite control.

Way forward

In conclusion, GLP-1 is a powerful hormone that plays a crucial role in regulating hunger, glucose metabolism, and overall metabolic health. While GLP-1 medications may offer a quick fix for weight loss, they come with potential side effects and long-term concerns, including muscle loss, mental health risks, and the return of cravings.

By focusing on natural ways to boost GLP-1, such as incorporating yerba mate, allulose, a low-ultra processed diet, collagen peptides/protein and whole foods, and optimising sleep, we can promote a healthier metabolism without the harsh side effects. Small changes, such as eating food in the right order, chewing thoroughly, and adding lemon extract or apple cider vinegar to our routine, can also make a significant difference in supporting GLP-1 production.

With these smarter dietary choices and lifestyle habits, you can take control of your health, manage cravings more effectively, and create a sustainable approach to improving metabolic health. By prioritising natural methods, you're not only supporting your body’s natural functions, but you're also setting yourself up for long-term success without relying on medications or quick fixes.

Take the time to implement these simple yet powerful strategies into your daily life – and watch your metabolic health thrive in a balanced, positive way!

*Disclaimer:

The information provided in this blog is for educational and informational purposes only and should not be construed as medical advice. While every effort is made to ensure accuracy, the content is not intended to replace professional medical consultation, diagnosis, or treatment. Always seek the guidance of a qualified healthcare provider with any questions regarding your health, medical conditions, or treatment options.

The author is not responsible for any health consequences that may result from following the information provided. Any lifestyle, dietary, or medical decisions should be made in consultation with a licensed medical professional.

If you have a medical emergency, please contact a healthcare provider or call emergency services immediately.