Boosting GLP1s with Phentermine
Reports of combining GLP1s with Phentermine suggest superior results. What is Phentermine and how can it be used with GLP1s?
Reports indicate that doctors are increasingly suggesting use of Phentermine with GLP1s like Ozempic or Mounjaro (active ingredients being Semaglutide and Tirzepatide respectively) to boost it's effects.
Check out our quick explainer
Phentermine isn't new – it's actually a "pre-GLP1" prescription drug, but it seems to "pair well" with other weight loss drugs (in the past, Topiramate) and that trend has not changed.
In particular, the personal report (i.e. n=1 anecdata) noted that previous to combining Phentermine, Wegovy was ineffective – after switching to Mounjaro + Phentermine lead to a loss of 20kg in 6 months.
At this point it is clear that GLP1s are effective on their one, but the somewhat unknown quantity (to some) here is Phentermine. let's dig into it.
What is Phentermine?
Phentermine is actually one of the most prescribed drugs for weight loss (this is likely due to it's pre-GLP1 popularity) – and it's been around for an incredibly long time:
Contributors to Wikimedia projects
In 1959, phentermine first received approval from the US Food and Drug Administration (FDA) as an appetite suppressant.[43] Eventually a hydrochloride salt and a resin form became available.[43]
Yes, Phentermine has been around for over 65 years.
Obviously this bodes well for safety and general understanding over time of the drug, so we're unlikely to see sudden changes in it's side effects or how people react to it.
Even more practical, detailed information about Phentermine can be found at Medscape.com – down to images of the pills and dosing information:
Phentermine is normally sold under at least two brand names:
- Adipex-P
- Lomaira
While Adipex-P is much older (and thus doesn't have a nice marketing site and is widely available), Lomaira is still quite actively marketed as a weight loss solution:
How does Phentermine actually work?
Where as GLP1s bind to GLP receptors in various parts of the body (most importantly, the brain), Phentermine is known to work in the brain to suppress appetite.
Phentermine is actually a kind of amphetamine, according to Wikipedia:
Phentermine, also known as α,α-dimethylphenethylamine or as α-methylamphetamine, is a substituted phenethylamine and amphetamine.[51][52][53] It is the derivative of amphetamine in which a second methyl group is present at the alpha carbon.[11][51][52][53]
There are many kinds of amphetamines (infamously some very illegal kinds), but clearly Phentermine is a legal substance with a specific goal. Another similar example might be Ritalin, an stimulant used in the treatment of Attention Hyperactivity Deficit Disorder (ADHD):
Contributors to Wikimedia projects
What are the side effects of Phentermine?
Common side effects of Phentermine include:
- Faster heart rate
- Sleeplessness
- Nervousness
- Constipation
While the above side effects aren't very high risk, some meta-analyses (covered later in this article) uncovered more nervous system-related side effects:
- Dysgeusia (distorted sense of taste)
- Paresthesia (tingling/pins and needles under the skin)
- Disturbance in Attention
- Irritability
- Hypoesthesia (numbness/loss of sensation)
- Dizziness
On average the obvious conclusion seems to be that Phentermine is safe – it does not at present cause irreversible side effects, and the most common side effects are relatively benign.
Phentermine may seem to have limited side effects, but every case is different and medical professionals are best suited to advise individual patients.
Phentermine was previously combined with Topiramate
Phentermine has also been combined with Topiramate in the past. We've written about Topiramate before here, as part of "life before GLP1s":
GLP1.Guide Staff
The combination of Phentermine was beneficial, and helped to boost the effects of Topiramate. This combination was (and likely still is) in wide use, and has been researched over the years.
What does the research say?
(2006) Phentermine usage in Korea
Research into Phentermine usage in Korea noted the widespread use of Phentermine as early as 2004:
This research set a easy to understand baseline:
Mean decrease of both body weight and waist circumference in phentermine-treated subjects were significantly greater than that of placebo group (weight: -6.7 ± 2.5 kg, p < 0.001; waist circumference: -6.2 ± 3.5 cm, p < 0.001).
Significant number of subjects in phentermine group accomplished weight reduction of 5% or greater from the baseline and 10% or more (p < 0.001).
Not only was Phentermine widely used and effective, there were also relatively few serious negative side effects:
Dry mouth and insomnia were the only statistically significant adverse events that occurred more frequently in phentermine group. Most side effects of phentermine were mild to moderate in intensity.
They go on to conclude that Phentermine was effective in producing weight loss and shrinking waist sizes without problematic side effects for healthy Korean people.
(2016): Phentermine + Topiramate
A meta analysis (i.e. not a trial) was done on Phentermine & Topiramate:
Steven M Smith
This research covered multiple trials for the Phentermine + Topiramate combination that were performed:
- EQUIP
- CONQUER
- SEQUEL
They found that significant weight loss was achieved with the combination:
After 56 weeks of treatment, percent weight loss achieved with PHEN/TPM was 10.6%, 8.4%, and 5.1% with 15/92 mg, 7.5/46 mg, and 3.75/23 mg, respectively (p < 0.0001).
The 52-week extension study (SEQUEL) showed maintained weight loss over 2 years with 9.3% and 10.5% weight loss from baseline for 7.5/46 mg and 15/92 mg PHEN/TPM (p < 0.0001).
A significantly higher proportion of patients achieved greater than 5%, 10%, or 15% weight loss with PHEN/TPM compared with placebo.
Significant reductions in waist circumference, fasting triglycerides, and fasting glucoses were also attributable to PHEN/TPM.
The drug was generally well tolerated in clinical trials. Adverse reactions occurring in 5% or more of study subjects included paresthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth.
It bears repeating – Phentermine was found to be incredibly safe and effective when combined with Topiramate, across multiple studies and it has produced positive health outcomes:
- Reduced body weight
- Reduced waist circumference
- Reduced blood glucose
- Reduced triglycerides
(2021): Phentermine + Topiramate in Adults (Meta analysis)
A meta analysis (i.e. not a trial) study was done on Phentermine + Topiramate in adults, which confirmed findings that Phentermine was effective:
Xiang-Guo Lei
Coarsely, Phentermine + Topiramate enabled average 7.73 kg loss in comparison to placebo:
Phentermine/topiramate therapy resulted in an average weight loss of 7.73 kg (95% CI: 6.60-8.85) in general compared with placebo.
This meta analysis also surfaced nervous system side effects that were somewhat under-reported.
(2022): Phentermine + Topiramate in Children
Going forward 15+ years, the Phentermine + Topiramate combination was well known and being researched, even for use with adolescents:
Aaron S Kelly
This trial was relatively small, but it did go over 56 weeks and produced results that are worth discussing:
- Patricipants were roughly 14 years of age
- 54.3% of participants were female
- 10.44% of body weight was lost on average for top dose
- 8.11% of body weight was lost on average for mid dose
- 51.8% of participants had an adverse event
- Two serious cases of adverse events occurred
What this study found was that triglycerides were only slightly reduced, which was worth noting.
Phentermine with modern GLP1s
It seems that Phentermine's usage in the age of Topiramate has paved it's way to it's usage with GLP1s.
Unfortunately, there are no studies of the combination yet, but the combination has clearly been starting to grow in adoption and use.
GoodRx has a great summary:
One time this combination might be considered is if you’re using Mounjaro for diabetes but haven’t met your weight-loss goals. In this instance, experts say adding a weight-loss medication could be an option. But it’s not right for everyone.
Given the research-backed safety of Phentermine (and GLP1), we're inclined to agree:the combination of Phentermine and GLP1s is not well researched (unlike Phentermine and GLP1s separately) – it's hard to know what the effect will be and it's unlikely right for absolutely everyone.
Side effects of Phentermine and Mounjaro, side by side
The table included by GoodRx is excellent:
| Side effects phentermine and Mounjaro share | Side effects unique to phentermine | Side effects unique to Mounjaro |
|---|---|---|
Common:
Rare:
|
Common:
Rare:
|
Common:
Rare:
|
