GLP-1s After 45: What They Can (& Cannot!) Do, & What Women Should Ask First

We’ve written a lot about GLP-1 receptor agonists (GLP-1 RAs) at 10almonds, so it’s time to assemble the information we think is most important, into one place.

What GLP-1 drugs can do

GLP-1 drugs mimic a natural gut hormone (namely, Glucagon-Like Peptide 1) that increases feelings of fullness, reduces hunger, and slows stomach emptying. This can also help regulate blood sugar and insulin, which for many people can make it easier to eat less and sustain a calorie deficit, leading to weight loss.

Some (semaglutide, liraglutide, tirzepatide, retraglutide, etc) are widely used to aid weight loss, but GLP-1 drugs were originally developed for diabetes management.

We wrote about that back in one of our earliest articles on this topic: Semaglutide for Weight Loss ← this was our article from back in the day when its popularity was just starting to rise

…and indeed, based on what’s now quite a large body of evidence, we would generally say that the various GLP-1 drugs can often help users lose 15–25% of their body weight*, when taken as appropriately prescribed for weight loss.

*The numbers do vary a lot, but that range is typical of what we see in research, for example:

• For data on semaglutide specifically, see this paper: Semaglutide as a GLP-1 Agonist: A Breakthrough in Obesity Treatment
• For comparisons of other compounded drugs, this one is very helpful: Weight Reduction with GLP-1 Agonists and Paths for Discontinuation While Maintaining Weight Loss (more on that later)

What they can’t do

However, examining only the benefits would overlook the matter of “if it works”, because for some people they simply don’t.

So, one thing they can’t do is “work for everyone”.

To give some more up-to-date numbers for two of the most talked-about compounded drugs of this kind, semaglutide and tirzepatide, let’s look at a recent systematic review and meta-analysis of randomized controlled trials (RCTs):

❝Twenty-one trials met the inclusion criteria (n = 7024 in pairwise analyses). Across 16 placebo-controlled trials, a higher proportion of participants achieved weight loss with GLP- 1–based agents than with placebo: 78.54% (3231/4114) versus 26.53% (772/2910); pooled odds ratio: 11.37 (95% confidence interval: 8.10–15.98), P < .0001; I² = 82%. In the network meta-analysis, tirzepatide and semaglutide ranked highest (surface under the cumulative ranking curve 91.2% and 85.4%, respectively).❞

So in other words, by those numbers there’s a little over 1 in 5 chance you will be a “non-responder” and it just won’t work for you.

You can read this paper in full, here: GLP-1 receptor agonists for weight loss: A systematic review and meta-analysis of randomized controlled trials

Other studies have given slightly different numbers, but within the same ballpark, and we talked about some related issues here: Why Intermittent Fasting (& GLP-1 Drugs!) Might Not Work For You

Further, another thing they can’t do is manage emotional eating for you.

• If you are overeating in response to the sight and/or smell of tasty food, then (per a study we’ll cite in a moment) it could be you will benefit well from GLP-1 RAs in the long-term
• If you are overeating for emotional reasons (e.g. because of depression, or as a coping strategy to deal with stress/anxiety, for example) then probably GLP-1 RAs cannot be replied on to help you as much.

By “cannot be relied on” does not mean you will necessarily be a “non-responder” as we described above, but it does mean that if you are in that second category, it’s likely your results may be intermittent at best.

You can read this paper in full, here: Association between eating behavior patterns and the therapeutic efficacy of GLP-1 receptor agonists in individuals with type 2 diabetes: a multicenter prospective observational study

While we’re on the topic of things they can’t do…

Common misunderstandings to avoid

A very common misunderstanding is to think “I’ll just take it to lose this weight, and then stop and maintain my lower weight by myself”.

It’s a very tempting line of thought, but, as a general rule of thumb, it doesn’t work out that way, and in fact, those who stop using GLP-1 RAs for weight loss appear to be sometimes more likely to put on weight more quickly than before: What Happens If Your GLP-1 Supply Is Temporarily Interrupted? ← still, this does show that a temporary interruption doesn’t necessarily have to erase all progress

Attentive readers will remember: Weight Reduction with GLP-1 Agonists and Paths for Discontinuation While Maintaining Weight Loss

Perhaps the biggest misunderstanding to avoid is the false belief that one can just take the regular injection, it’ll work its magic, and you’ll automatically lose weight and be healthier.

On the contrary, when GLP-1 drugs do work for weight loss, it’s typically alongside a healthier diet and a good exercise routine—the drug may make it easier for you to adhere to a healthier diet and avoid overeating, but at the end of the day, it’s not doing your grocery shopping for you!

And nor is it going to the gym for you. On which note…

Some menopause-specific considerations

There are many things we need to take particular care of during and after menopause, and three important ones are:

• Maintaining healthy body fat levels
• Maintaining healthy muscle mass
• Maintaining healthy bone mineral density (BMD)

The first one, maintaining healthy body fat levels GLP-1 drugs can be famously good at helping with (since the challenge for most people is keeping fat off, not keeping it on).

The second one, maintaining healthy muscle mass, is connected to both fat levels (because muscle costs energy to maintain, and thus raises your basal metabolic rate, and thus can help hasten/maintain fat loss) and BMD (because the body will not build strong muscles on weak bones, so building/maintaining muscle mass helps cue to body to build/maintain strong bones).

Maintaining healthy muscle mass and bones requires healthy diet (can’t build/maintain those things out of thin air) and healthy exercise (the body won’t build/maintain those things unless cued to do so).

As you’ll remember from the previous section, GLP-1 drugs can help us improve our diet by cutting down on “food noise”, but at the end of the day it’s on us to actually eat well and exercise well.

In particular, it’s important to take a holistic approach, and make sure that you have a plan not just for losing weight, but also for maintaining muscle and bone, for example:

• Weighing the risk of GLP-1 treatment in older adults: Should we be concerned about sarcopenic obesity?
• GLP-1-derived therapies and sarcopenia: plea for a specific focus on at risk special populations
• Preventive Strategies to Reduce Sarcopenia Risk During GLP-1-Based Anti-Obesity Therapy

So, whether you take GLP-1 drugs or not, it’s still important to get exercise (especially load-bearing resistance exercise), and eat well (including getting enough protein, calcium, and vitamin D).

What should you look for when assessing a provider

If you’re thinking of starting GLP-1 treatment, then there are some important considerations to bear in mind, and questions to ask.

• Which GLP-1 drug? As there are an array of options, including FDA-approved GLP-1 drugs like Wegovy^® and Ozempic^® (semaglutide) and Zepbound^® and Mounjaro^® (tirzepatide), or compounded semaglutide and tirzepatide prepared in the US by licensed pharmacies when a brand medication isn’t the right fit, it’s important that your provider gives clear information about what they are offering and why.
• What dosage? A lot of providers may try to hide efficacy claims behind not mentioning the dosages used, which can make comparisons from one drug to another a little unfair. So, look for a provider that is transparent in that regard, too.
• Who’s prescribing, and how? If you’re in the US, look for it being prescribed by US-licensed clinicians, and you’ll want to see them doing this after conducting an assessment to ensure it’s actually appropriate for you (it may be very useful for many, but it isn’t for everyone!).
• Is there ongoing monitoring? It shouldn’t be a case of “prescribed-and-you’re-done”; there should be an ongoing process of checking how it’s actually going for you, to ensure that the drug and its dosage are indeed working as expected, are continuing to do so, and no additional problems have arisen.

Lastly, some important things to note

This educational article has been written by our usual 10almonds writing staff, but we do need to make clear it was sponsored by Pallas Health. Speaking personally (hi, it’s me, your regular 10almonds writer), I’ll never write something that I don’t believe to be true, not for 10almonds and not for any sponsor. In this case, I didn’t even have to tell anyone “no”, because Pallas made very clear they didn’t even want me to feel any pressure to make the article flattering, and that I should genuinely address the pros and cons, and talk openly about what readers should ask them or any other provider. This I have happily done.

Two other things that it’s important to mention, for legal and regulatory reasons:

Compounded medications are prepared on a per-patient basis by US-licensed compounding pharmacies, regulated under federal law (FDCA §503A) and by state boards of pharmacy. While these pharmacies are highly regulated, the compounded medications themselves are not FDA-approved, are not generic versions of brand-name drugs, and have not been evaluated by the FDA for safety, efficacy, or quality. Clinical trial outcomes for the FDA-approved products have not been established for compounded preparations. Individual results vary.

Pallas offers both FDA-approved and compounded medications. Compounded medications are not FDA-approved and are not generic versions of brand-name drugs. Eligibility and treatment are determined by a US-licensed clinician; results vary. Private pay only (no insurance). Operated by Brentmoor, Inc.

With all that in mind, if you’d like to check out Pallas Health and their GLP-1 treatment options, here is a link to learn more.

Take care!