45 Natural Semaglutide Alternatives for Powerful Weight Loss (Safe & Natural GLP-1 Activators)

Semaglutide, Ozempic, Wegovy, Mounjaro, and other blockbuster weight loss drugs constantly make headlines.

Most users report staggering and unparalleled weight loss—they clearly work.

Could these be the fat loss magic bullet?

Most experts won’t tell you, however, that these drugs have glaring downsides. For many, they pose more risks than benefits.

Each of these substances belongs to a family called GLP-1 agonists.

There are all kinds of reasons to choose an over-the-counter GLP-1 alternative. Perhaps you’re on a budget, want to avoid nasty side effects, worry about long-term safety, or are simply looking for a natural replacement.

In this article, we’ll explore some of the strongest, safest, natural, and best GLP-1 drug alternatives for weight loss and replicate some of the same benefits.

Of course, none of this is medical advice and you should check with your primary healthcare practitioner before changing your current regimen.

What is GLP-1?

Glucagon-like Peptide-1 (GLP-1) is a peptide hormone produced in the intestine that helps regulate blood sugar levels by both stimulating the release of insulin from the pancreas and inhibiting the release of glucagon (another hormone that raises blood sugar levels).

GLP-1 also slows down the emptying of food from the stomach.

Most importantly, it activates a neural circuit called “POMC”. Activating POMC neurons makes you eat less.

Leading to a feeling of fullness, mitigating cravings, and improving weight loss.

Medications based on GLP-1 are often used to help type 2 diabetics control their blood sugar levels.

Due to their potent appetite and craving-suppressing effects, they’ve become a top pick of celebrities looking for magic bullet weight loss pills.

Dangers of GLP-1 Drugs

Note that weight loss, cravings, and digestion are far more complicated than the few hormones mentioned here.

GLPs are but one substance in an intricate web of metabolism.

So, unsurprisingly, heavily and forcibly tweaking GLP has unintended side effects and consequences. And at the same time, yields sub-par results.

Here are the currently approved GLP-1 agonist medications:

• Ozempic (semaglutide)
• Wegovy (semaglutide)
• Rybelsus (oral semaglutide)
• BYDUREON BCise (exenatide extended-release)
• Byetta/Bydureon (exenatide)
• Victoza (liraglutide)
• Trulicity (dulaglutide)
• Tanzeum (albiglutide)
• Adlyxin (lixisenatide)
• Mounjaro (tirzepatide)

Retatrutide is an emerging and promising triple agonist of satiety related hormones (GLP-1, GIP, and glucagon).

Another related form of anti-diabetes drugs includes a class called “DPP-4 inhibitors”. DPP-4 is an enzyme that rapidly breaks down GLP-1 and related hormones.

By reducing the activity of the enzyme that degrades GLP-1, this mechanism also keeps levels high [R].

These medications, especially when used off-label as a weight loss hack, have many issues. Blunting pleasure from eating (and all life pleasure, for that matter), dysregulating biomarkers, and dubious long-term efficacy are only some of them.

I urge you to read my post on the long-term dangers and side effects of GLP-1 peptide drugs.

While there are great peptides for weight loss, it’s always better to use safer natural options to mimic similar effects.

Biohacker’s Master List of Better, Safe Long-Term Alternatives to GLP-1 Drugs

I’ve combed through hundreds of research papers, looking for the top GLP-1 stimulating foods, supplements, and lifestyle habits.

The research here is still developing. We need a ton more solid science to verify the claims, especially when it comes to GLP-1s impact on humans.

Nevertheless, here it is…

The complete list of natural GLP-1 stimulators:

1. Calocurb
2. Oats & oatmeal [R]
3. Raw honey (fructose) [R, R, R]
4. Butyrate & short-chain fatty acids [R, R, R]
5. Yerba mate [R]
6. Yam extract [R, R, R]
7. Black cumin seed (thymoquinone) [R]
8. Oleoylethanolamide (OEA) [R, R, R]
9. MUFAs/omega fatty acids [R, R]
10. Prebiotics & resistant starches [R, R, R]
11. Probiotics [R, R, R]
12. Whey [R, R, R]
13. Coconut (galactomannan) [R]
14. Berberine (via intestinal cells) [R, R, R, R]
15. Cinnamon [R]
16. Palatinose (isomaltulose) [R]
17. Sugar/glucose [R]
18. Turmeric/curcumin [R, R, R]
19. Chlorogenic acid [R]
20. Pomegranate extract/MitoPure/Akkermansia [R]
21. Momordica charantia extract [R]
22. Sorghum whole grain [R]
23. Gardenia [R]
24. Olive leaf extract [R]
25. Grape seed extract [R]
26. Resveratrol [R, R]
27. Bile supplements [R, R, R]
28. Ginseng [R, R]
29. ALA/flax/chia [R]
30. Inulin/FOS [R]
31. Guar gum [R]
32. Glutamine [R, R]
33. Bitter melon [R]
34. Quercetin [R]
35. Berries & citrus [R]
36. Strawberries [R]
37. Cherries [R]
38. Grapes [R, R]
39. Avocados [R]
40. Leafy greens [R]
41. Sweet potatoes [R]
42. Broccoli [R]
43. Almonds [R]
44. Beans [R]
45. Spirulina/chlorella/fucoidan micro-algae [R, R]
46. GLP-1 Shake (below)

A lot of this research is weak and/or based on other non-human models.

For example, many of the fruits, vegetables, and legumes listed here indirectly stimulate GLP-1 through Abscisic Acid (ABA) [R].

Time will tell how much they carry over to humans. But at least they’re natural and safe.

Highest Impact Ways to Increase GLP-1

Of the countless ways to increase levels of GLP-1, several stand out as having the greatest impact on GLP itself and many related hormones/pathways/processes.

If your goal is to combat cravings, suppress appetite, and accelerate weight loss, these are the foundations to start with.

The GLP-1 super shake

We can combine several of the above ingredients into a tasty milkshake that naturally boosts levels of GLP-1 and other similar “incretin” hormones.

In Joel Greene’s new book called The Way, he shares a recipe for a “GLP-1 Super Milkshake”. It’s powerful, natural, delicious, and safe.

The ingredients:

• 1G Stevia
• 1 Tablespoon honey
• 20 Grams grass-fed whey protein powder
• 1 Tablespoon nut butter
• Optional: 1 Teaspoon resistant starch

The directions:

1. Mix everything together
2. Optionally top it with low-calorie coconut whipped cream
3. Enjoy

Can’t tolerate one of those ingredients? No problem.

Joel recommends the following ingredient swaps:

• Instead of whey protein —> pea protein, hemp protein, collagen protein, or beef isolate
• Instead of nut butter —> coconut oil, sunflower seed butter, greek yogurt

Each ingredient specifically targets GLP-1 release and/or makes it work more effectively. You can find a thorough breakdown of how each ingredient works in Joel’s book.

For the best results, enjoy the shake as a “preload meal” 15 minutes before dinner.

Meal timing

When and how often you eat can impact hunger and cravings. In the brain, POMC neurons drive you to eat less. Opposing them, Agouti Related Protein neurons (AgRP) neurons drive you to eat more.

GLP-1 in the gut stimulates POMC.

The more heavily you fast, the more the AgRP neurons dominate, leading you to overeat.

If naturally maximizing GLP-1 levels is your goal, fasting appears counterproductive. Two small trials show that both short 16-8 intermittent fasting and also OMAD/20:4 fasting slightly decrease levels [R, R].

Exercise

Movement has a plethora of benefits, including acting as a natural GLP-1 agonist.

Exercise causes GLP-1 to rise almost immediately after sessions [R, R]. This includes all forms of movement, from vigorous walking to resistance training to aerobic exercise.

Exercise can also help people with T2D use GLP-1 more efficiently [R].

Should you choose to use things from the master list of alternatives to the prescription drugs themselves, exercise may help them work better.

Ample quality sleep

One of the first places to start naturally increasing GLP-1 levels is through your sleep.

Sleep is a vital component of overall health, especially for optimal body composition.

Inadequate sleep disrupts the hormonal (endocrine) system. Deprivation leads to overeating, poor decision-making, extreme hunger, less satisfaction, and eventual weight gain.

Sleep deprivation is also associated with less GLP-1 production.

Try to get 7.5-9 hours of total sleep time per night. Total time asleep is often significantly shorter than time in bed. I recommend getting started the easy way by biohacking your sleep.

Protein

Dietary protein is one of two essential macronutrients required for life. It’s also the macro most associated with satiety, stable blood sugar levels, weight loss, and enhancing overall health.

There’s a thermic effect of protein. Each time you consume it, about 30% of the calories get “wasted” during digestion. So if you eat 100 calories of protein, you only absorb 70.

Then there’s the increase of satiety hormones like GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) [R]. There’s also the blunting of the hunger hormone ghrelin making protein a foundational way to mimic the effects of GLP-1 drugs [R].

Some of the top sources include meat, poultry, fish, grass-fed whey protein powder, dairy, legumes, and nuts.

Fiber

Fiber had a longstanding role as an integral component of healthy diets, but that’s wrongly fallen by the wayside over the last decade.

Fiber-rich foods, like grains, legumes, some nuts, fruits, and vegetables check a number of GLP-1-activating boxes. You’ll notice that many of the foods in the above list contain appreciable fiber.

Not only do they provide satiety, but they also activate some of the same mechanisms/effects/pathways. Causing feelings of fullness, slowing digestion, and helping regulate appetite.

Some forms of fiber even work as prebiotics to feed key probiotics, both of which influence GLP-1.

Some great sources include:

• Beans
• Lentils
• Peas
• Avocado
• Flaxseeds
• Chia seeds
• Berries
• Broccoli
• Cauliflower

These foods are also quite low in net calories, making them great for weight loss.

Polyphenols

Polyphenols are a class of natural compounds found in plants that have a wide variety of beneficial properties. They are abundant in foods like fruits, vegetables, herbs, spices, tea, coffee, and red wine.

Polyphenols provide many of the benefits attributed to health superfoods.

They help improve the hormones related to appetite by interacting with gut microbiota and intestinal cells.

Polyphenols also directly increase the secretion of GLP-1, increase fat burning (oxidation), and boost metabolism [R].

Foods highest in nutrients also tend to have high levels of polyphenols, and these show the best GLP-1 stimulation [R].

Since typical healthy diets readily include polyphenol-rich foods, this should be simple to incorporate. Or, you can take a polyphenol supplement.

Here’s a full guide on polyphenols’ benefits, uses, and best food sources if you want to learn more.

Control stress

Intense chronic stress destroys our overall health, including counteracting the same things these medications seek to do.

That’s right, heavy stress actually has the opposite effect on the body as GLP-1s.

During periods of stress, the body releases cortisol and other stress hormones to help deal with the stressor.

These stress hormones drive cravings, blood sugar swings, insatiable appetite, body fat gain, and even reduced GLP-1 secretion.

Stress itself is an inevitability and not a problem. When it becomes intense and prolonged, however, it takes a huge toll

I recommend getting outside and going on a walk, practicing a few minutes of deliberate breathwork, meditating, using technology, or any of these stress biohacks to quickly get back on track.

Probiotics

Probiotics are a class of beneficial bacteria that promote gut health and balance the community of microorganisms living in our intestines (the gut microbiome).

The health of your gut microbiome correlates highly with your overall health.

Certain strains of these bacteria increase the release of GLP-1, which promotes feelings of fullness, reduces cravings, and supports weight loss.

Lactobacillus, Bifidobacterium, and Akkermansia have shown the greatest potential to increase GLP-1 [R].

You can get some by adding probiotic-rich foods like yogurt, kefir, and sauerkraut into your diet. But most people benefit from using a specific synbiotic supplement.

GLP-1: One Key Piece of the Puzzle

Focusing on GLP-1 specifically has its use cases. Most people looking for an over-the-counter way to enjoy the benefits of the common drugs have better options.

Options that include optimizing GLP-1 in addition to the other myriad processes, biochemical pathways, and the entire bodily ecosystem.

Nearly 50% of your GLP-1 release is determined by genetics

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812410/

It’s not working in isolation; GLP-1 also impacts other hormones like insulin and glucagon [R]. It slows down stomach emptying, which impacts nutrient absorption, cellular detox, and the potential risk of infection [R].

Perhaps the nail in the coffin, however, is that GLP-1 has an extremely short half-life of 1-2 minutes. Then it gets degraded by an enzyme called dipeptidyl peptidase-4 (DPP-4).

That means that the body naturally breaks down within mere minutes. Bodily processes and timings all have their reasons.

Rather than trying to “break” one part of the body, the advanced biohacker focuses on optimizing the entire system.

Then cravings, appetite, and eventual weight loss become easier. With far lower risk of a massive rebound.

Natural Ways to Beat Cravings, Feel Full, & Drop Weight

The weight loss market popularized GLP-1 drugs as they showed the potential to work like magic bullets.

Now that their novelty has worn off, the dark side and potential side effects have well-studied biohackers questioning the safety and long-term effects of their use.

One thing’s clear…

Weight loss is about a lot more than incretins like GLP-1.

As I’ve highlighted in this mega list, we have all kinds of tools to naturally, powerfully, and safely increase GLP-1 levels.

The absolute best and strongest natural alternative to Ozempic currently is Calocurb. Two capsules in the morning crushes my appetite and cravings for most of the day. Only safer and more natural.

And the best strategy to biohack your weight loss considers many pathways/systems/organs rather than “blasting” any one in particular.

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Now, over to you. Have you tried any of these natural alternatives to GLP-1 weight loss drugs? Let me know your experience in the comments of this article!