Life before GLP1s: Topiramate
Wondering what the world was doing before GLP1s? We discuss Topiramate, a popular appetite suppressant.
The GLP1 revolution seems to be in full swing. Drugs like Ozempic, Wegovy, Mounjaro, Zepbound and others make news every day, and people can't get enough of them. The phrase "GLP1 Receptor Agonist" has never been said more in history.
Check out our quick explainer
But what was life like before Ozempic and the other GLP1 Receptor Agonists?
Weight loss has had a lot of ineffective treatments – diets that don't work, and bad advice is everywhere. That said, there were clinically-approved solutions that did work before GLP1 – Topiramate is one of them.
What is Topiramate?
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Topiramate is an seizure-reduction and anti-psychotic (mood stabilizing) drug that was originally discovered in 1979 by McNeil Pharmaceuticals.
The drug was discovered to have other uses ("off brand") and weight loss is one of them.
The most known name brand drug is "TOPAMAX", which is sold by Mylan Pharmaceuticals, and started being sold by the FDA in 1996.
Is Topiramate FDA approved?
Yes, Topiramate (TOPAMAX) is FDA approved, and at this point a generic version even exists.
The last patent for Topiramate expired in 2009.
Qsymia: an FDA-approved weight loss medicine
The combination of Topiramate with a compound called Phentermine is FDA approved for weight loss.
There are certainly a lot of side effects to take into account but the fact that the combination is FDA approved speaks to it's efficacy.
Who makes Topiramate (TOPAMAX)?
TOPAMAX is currently being produced by Mylan Pharmaceuticals, though a generic now available which means that many other pharmaceutical companies may also produce it. Johnson and Johnson now produces TOPAMAX through a subsidiary:
How does Topiramate work?
Topiramate is in a class of medicines called anti-convulsants. With relation to weight loss it primarily helps keep you feeling full longer.
A great analysis paper to read is this one:
Irza Wajid
They illustrates the mechanism of action of Topiramate with the following graphic:
Topiramate does alot of things, the complicated effects of which can be hard to understand (and likely explain the variety of side effects). The paper goes on to state:
Although the biological mechanism behind TPM-induced weight loss is not well-described, possible mechanisms include lowering calorie intake, decreased fat gain, and decreased triglycerides and cholesterol levels [8]. Studies show that TPM reduces energy deposition without changing food consumption by disrupting efficient energy utilization [9].
From this we can glean that Topiramate seems to make some changes to the body that make your body more inefficient – i.e. being less able to save energy (store fat) and use energy more than you would otherwise.
A review by Verotti et al. endorses the ability of TPM to induce weight loss, which is most significant in patients with a high BMI. Verotti et al. also reported the possibility that TPM reduces binge eating behavior by altering the reward pathway associated with the food [9].
In general, it's just not well known exactly how Topiramate works (and in combination with Phentermine).
Qysmia = Phentermine + Topiramate
We've mentioned Qsymia which is the combination of Phentermine and Topiramate – these drugs together form an (FDA Aprpoved) drug.
The drug is well known and has various resources on the internet dedicated to discussing the risks and benefits:
What are the side effects of Topiramate?
Compared to GLP1s, Topiramate is much more fraught – there are some quite intense side effects, and in the past Johnson & Johnson (and their subsidiaries) have been sued for negative side effects that weren'r properly disclosed.
Topiramate can be difficult to take at night, and could cause trouble sleeping. Topiramate also has a risk of being habit forming – i.e. addictive.
Suddenly stopping taking Topiramate is also not recommended, and can lead to seizures.
Topiramate also has a huge risk of birth defects (disclosure of which was lacking which is why legal action was taken against them).
Scott Hensley
For example Qsymia (the combination of Phenteramine and Topiramate has the following side effects):
- Headaches & Dizziness
- Numbness, burning, or tingling in the hands, feet, face, or mouth
- Decreased sense of touch or ability to feel sensation
- Difficulty concentrating, thinking, paying attention, speaking, or remembering
- Exhaustion and/or excessive tiredness
- Dry mouth & unusual persistent thirst
- Changes or decreased ability to taste food
- Nausea
- Diarrhea
- Constipation
- Heartburn
- Painful menstrual periods
- Pain in the back, neck, muscles, arms or legs
- Tightening of the muscles
- Painful, difficult, or frequent urination
- Bair loss
- Fever, sore throat, cough, congestion, or other signs of infection
And as far as serious side effects there are more:
- Racing or pounding heartbeat that lasts several minutes
- Sudden decrease in vision
- Eye pain or redness
- Fast, shallow breathing
- Severe pain in the pack or side
- Blood in urine
- Rash, hives, peeling, or blistering skin
It all adds up to this – Topiramate has dramatically more and more serious side effects than the current crop of GLP1 Receptor Agonists – the new GLP1s are clearly quite impressive.
How is Topiramate similar to GLP1s?
While there aren't many similarities in the two drugs, one thread is common – Topiramate is very much a brain drug. It's benefits seemingly come from it's effects on the brain, and that's how many GLP1s seems to reach their highest efficacy.
Topiramate's history as an seizure-reducing and anti-psychotic speaks to it's effects on the brain, and it's off-label use is certainly similar to GLP1s of today (though GLP1s for weight loss should soon be on-label for the majority of them)
The earlier cited paper also refers to this effect in a linked study:
A review by Verotti et al. endorses the ability of TPM to induce weight loss, which is most significant in patients with a high BMI. Verotti et al. also reported the possibility that TPM reduces binge eating behavior by altering the reward pathway associated with the food [9].
This is quite similar to GLP1s binding to receptors in the brain (and dampening the effects of things like "food noise")
Should you take TOPAMAX or Qsymia?
Only a qualified medical professional (your doctor) can advise on whether you should or should not take a particular medicine or treatment.
That said, looking at the side effects and general lack of understanding around possible avenues via which Topiramate (TOPAMAX) with or without Phentermine (Qsymia) work, it's difficult to consider them a better choice than GLP1 Receptor Agonists.
We've done quite a bit of research on whether GLP1s are safe, and they have dramatically less adverse effects:
GLP1.Guide Staff
