Over the last year, I have gotten numerous questions about GLP medication for weight loss. In the beginning, I was hesitant about them, wanting to wait to get more information, potential side effects, and possible long-term consequences.
What Seems Promising:
1. Metabolic Repair
- Reversing metabolic dysfunction
- Reducing and reversing diabetes and insulin resistance
- Reducing cardiovascular disease
- Stubborn weight loss
2. Appetite and Brain Effects
- Quieting food noise
- Psychological benefit
- Quieting reward-seeking effects
3. Inflammation and GI Effects
- Anti-inflammatory benefits
- Positive possible benefit on the gut microbiome
- Potential positive effects of reversing fatty liver
4. Cancer Context:
- Obesity driven cancers from elevated insulin
What Seems Worrisome:
1. Body Composition Concerns
- Muscle loss
- Bone density loss and bone health
- Skin integrity and sagging
- Hair loss
2. GI and Microbiome Concerns
- GI side effects: constipation, intestinal blockage from reduced motility, nausea/vomiting, GERD
- Negative impact on the gut microbiome from constipation and reduced motility
3. Psychological and Dependency Fear
- “Addiction” or fear of not being able to stop, or the weight will pile back on
- Actual dependency and the need to continually take GLP medications
4. Cancer Concerns:
- Thyroid cancer (those with a history of MTC/MEN2 cannot take)
- Pancreatic cancer
- Other cancers
The million-dollar question:
So how do we balance the pros and minimize the potential risks?
Before we hash that out, let’s learn more about what GLP-1 medications are.
How They Work:
Semiglutide and trizepatide are both GLP-1 receptor agonists.
It imitates a hormone our bodies naturally make called Glucagon-like peptide-.
GLP-1 is released from our intestines after a meal and tells our body that we are satiated and have eaten.
More about GLP-1 receptor agonist:
- Decreases hunger
- Reduces ‘food noise’
- Decreases reward-driven eating and possibly reward behavior in general. Meaning it could have a positive effect on dopamine chasing like gambling, ETOH, smoking, drugs, etc…
- Slows gastric emptying so you feel full longer and eat smaller portions. But this is not an excuse to starve yourself.
GLP-1 receptors are everywhere:
Well, not everywhere, but they are located in your gut, pancreas, brain (hypothalamus, brain stem), endothelium/myocardium (cardiovascular system). This is why they can have a multifactorial effect and not just on appetite.
The Difference:
The difference between trizepatide and semiglutide is that trizepatide is also a GIP agonist, while semiglutide is not.
There are reports that trizepatide has better effects and fewer side effects. Which also makes trizepatide a little pricier than semiglutide.
What is GIP?
GIP stands for glucose-dependent insulinotropic polypeptide, which enhances insulin secretion when glucose is elevated.
Note: It doesn’t stimulate insulin unless glucose from a meal is present.
Semeglutide: GLP-1 agonist
Trizepatide: GLP-1 agonist and GIP receptor agonist
So trizepatide hits two incretin pathways, while semiglutide hits one.
Indirect Effects:
But it is not about where the GIP and GLP-1 receptors are. There are more indirect effects.
If insulin sensitivity is better, there is less inflammation, appetite satiation, less food-noise and reward-driven eating, then the impact on your metabolic health, gut health, and cardiovascular health can be incredible.
And reducing overall elevated glucose in the case of diabetes can have a huge impact on health and longevity.
Visceral Fat is Bad For You:
There is fat, and then there is visceral fat.
Visceral fat, which is fat wrapped around your organs. As we get older (perimenopause and menopause), fat accumulation will start to be directed to inside your body, not the outside jelly-belly.
I mean, having superficial fat is not fun when you can’t fit into your jeans. But visceral is different. It is very inflammatory and can lead to chronic disease.
I have seen GLP-1 medications reduce visceral fat in practice many times.
There is a blood test called C-reactive protein (CRP) and highly-sensitive CRP (HS-CRP).
- CRP: measures inflammation in the body
- HS-CRP is more specific and sensitive for cardiovascular and metabolic inflammation.
Over the past 20 years, I have had a number of patients who had elevated CRP and HS-CRP. Yet, they were not ill, did not have cardiovascular conditions, and didn’t have anything that was causing them pain or inflammation.
What I have come to find out is that a high CRP and HS-CRP can point to the presence of visceral fat.
The Dark Side:
Well, GLPs sound like a dream come true: anti-inflammatory, anticancer, reduces chronic disease, helpful for the heart, and those jeans from 1996 get to fit.
But too much of a good thing is not a good thing.
Because taking a GLP medication and not using it properly could result in:
- Loss of Muscle: You don’t eat, the first thing you lose is muscle, and the very, very last to lose is fat.
- Loss of Bone: If you lose muscle, then you lose bone. Muscle and bone are tightly linked; when muscle strength declines, then bone density decreases. It might feel great to lose weight right now, but 5-10 years down the road, it could show up as reduced bone density if muscle and strength are not protected.
- Creepy Skin: If you are not eating bc your appetite is gone, your skin is going to show it. With limited nutrition and loss of fuel, your body is going to prioritize all calories to the important parts of your body, such as vital organs, brain, and heart. Skin and connective tissue are at the bottom of the totem pole, which could lead to crepey texture and loss of elasticity over time. This is especially seen in the face. Your face depends on subcutaneous fat, adequate protein, essential fats, and micronutrients for structure.
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Hair Everywhere, But Your Head: Hair follicles have a life cycle/phases.
- Anagen: growth phase
- Catagen: transition
- Telogen: rest/shedding
The body perceives loss of fuel/calories and deficient nutrition as a big stressor. Hair is a luxury. The body says, ‘I am choosing survival over luxury, and will push the hair follicles prematurely into the telogen phase hair loss (also known as telogen effluvium). What can be confusing is that it will show up weeks to months later, so people chalk it up to stress, not the dark side of GLP-1 meds. It shows up as diffuse shedding, and it is not permanent. But hair grows slowly, so once it falls out, it's going to take a long time to grow it back.
- Grumpy Gut: GLP-1 meds will slow down transit time, which sounds great to feel full longer. But if you become constipated, the bad bacteria/yeast/candida/pathogens can flourish and push out the beneficial bacteria. Your gut and GI are like a garden. Once it is overgrown with weeds and the flowers are dead, it takes a while to regrow it back
- Dependency: I have met plenty of people who are stuck on GLP-1 meds. They have taken too high a dose continuously; once they stop, the weight piles back on.
- Cancer, Cancer, Yikes! GLP-1 meds are not recommended for anyone with personal or family history of medullary thyroid cancer (MTC) or Multiple Endocrine Neoplasia type 2 (MEN2). Although for most people, current evidence doesn’t suggest GLP-1 meds increase other cancers. Concerns about pancreatic cancer have been studied extensively, and current data do not show a clear increased risk, though pancreatitis remains a clinical caution in susceptible patients.
That said, these meds are relatively new and widely used, so more data will continue to shape how we view and understand the full risk profile.
Back to our million-dollar question:
How Do We Balance the Pros and Minimize the Potential Risks?
GLP-1 medications can be powerful tools when used thoughtfully, but they are not shortcuts or stand-alone solutions.
The goal is not the highest dose, the fastest weight loss, or a number on the scale, but long-term metabolic health, strength, and longevity.
When dosing is individualized, lifestyle foundations are implemented, and the medication is used as a tool.
GLP-1s can help people move toward better health without sacrificing muscle, bone, hair, skin, or their relationship with food. As with anything in medicine, how we use the tool matters just as much as the tool itself.
Curious how I actually dose and individualize GLP-1 medications?
The paid article goes deeper into:
- Micro-dosing
- dynamic titration
- dose pacing
- therapeutic pauses,
- how to prevent dependency while protecting muscle, bone, skin/hair, and creating healthy lifestyle choices and supplements.
Thank you for reading, DrValorie
