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The Dark Side of Weight Loss Drugs

Posted by Dr Sandy on in Obesity | 127 Views | Leave a response

New weight loss drugs like Ozempic promise easy weight loss, but there’s a hidden danger—accelerated muscle loss and frailty over time.

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The Dark Side of Weight Loss Drugs: Uncovering the Hidden Risk of Muscle Loss

Semaglutide signing autographs

New weight loss drugs like Ozempic promise easy weight loss, but there’s a hidden danger—accelerated muscle loss and frailty over time.

Maybe you’re contemplating hopping on the latest weight loss CRAZE, maybe you’ve already managed to snag a prescription and you’re enjoying the benefits of  one of the new “Titans of Weight Loss”,

A quick introduction

The Titans of weight loss represent a new class of weight loss therapies, officially they are classed as incretin based therapies/mimetics.  They mimic the endogenous hormones, collectively referred to as the incretins, these gut hormones help to signal to the body that you’ve just eaten and that it is time to “take care” of the groceries.

“Taking care” of the groceries includes

  • Shooting a note to the beta cells of the pancreas to release insulin resulting in improved glycemic control
  • Keeping the contents of the stomach whooshing for a tiny bit longer i.e. slowing gastric emptying
  • And putting a stop to further grocery acquisition until such time as the current load has been processed so appetite is reduced and overall food intake is decreased.

The incretin mimetic family

The poster child is semaglutide, better known as Ozempic® and Wegovy®. Semaglutide’s pharmacological categorization is as a GLP-1 agonist (the GLP refers to glucagon-like peptide).

But the family is growing………

The incretin mimetic family of drugs

Add-ons include

  • Tirzepatide (which is a dual agonist pinging both the  GLP-1 and GIP receptor)
  • Retratrutide ( is a GLP-1 + GIP + glucagon agonist) all rolled into one. FANCY FANCY !

The question is should you hop on the band wagon ?

If you google right now, the answer would be HELL YES.   Even the “purists” in the functional medicine camp are singing their praises and the vast majority of research appearing in the big medical data base see the class of drugs as

“THE  MIRACLE we’ve been waiting for”

Sample of some of the titles of journal articles related to incretin drugs

and the thinking is…………let’s “ADD IT TO THE WATER”.

Hang on a minute

Well for the record…………… I am not a big fan.  Trained as a pharmacologist (this is someone who specializes in studying drugs), I see some BIG red flags.

Efficacy is NOT the issue

If the goal is to lose weight………….. they deliver.

This is the data from the STEP trial which put these guys on the map.

STEP trial data showing semaglutide efficacy in weight loss in non-diabetics

Effect of Once-Weekly Semaglutide, as Compared with Placebo, on Body Weight. Copyright 2021 Massachusetts Medical Society

A caveat : they seem to work better in clinical trials than in the real world.  In real world trials the weight loss is a little more moderate especially in people who are metabolically challenged.  This is not a BIG SURPRISE, this often happens in clinical trials, the reason, who goes into a trial is carefully monitored.

A close to 5 % weight loss, while not the whopping 15 % since in clinical trials,  is not too shabby and  the very act of losing weight more often than not improves many aspects of body chemistry, especially health parameters that are related to “obesity”.

Selective BETTER BODY CHEMISTRY

They DO NOT improve body chemistry in terms of insulin levels.

In fact quite the opposite, because of timing issues,  insulin levels are boosted morning, noon  and night.    And for me this is a concern, because a lot of the metabolic chaos that goes hand in hand with metabolic syndrome is rooted in insulin levels being high :  morning, noon and NIGHT.

They’re FOREVER DRUGS

You don’t take them, lose the weight and then STOP and live as a skinny individual thereafter.  If you STOP, the weight comes right back, here is data showing the extent of the weight gain.

Graph showing change in weight when taking semaglutide and then when stopping

Change from baseline in body weight by week in participants in the semaglutide arm, grouped by categorical weight loss from week 0 to week 68. © 2022 John P. H. Wilding et al Diabetes, Obesity and Metabolism

This data reveals a lot of the time people are NO BETTER off a year down the line.  And for a few unlucky souls, they are worse off than when they started.   Of course, this is not unusual – it is the fundamental problem with weight loss.

Losing the weight is relatively easy.  Keeping it off is the REAL CHALLENGE.

Natural but NOT natural

They are not the same as endogenous incretins, incretins are gut hormones, the drugs are primarily acting outside of the gut.

High circulating levels are NOT natural.

The impact of high circulating levels 24/7 long-term is UNKOWN.

But it is unlikely to be completely BENIGN. 

The UNKNOWN stems from the fact the drugs only came onto the market in 2021, so they just haven’t been around long enough to know what the long term impacts will be. There are hints of some serious adverse events e.g. pancreatitis.

They don’t fix body chemistry where it matters

What we do know….

They don’t FIX insulin resistance/hyperinsulinemia, actually they perpetuate it, because the way they lower sugar levels is by BUMPING UP insulin production, around the clock.

But the negative impact on metabolic health doesn’t stop here : let me explain.

Weight = fat and muscle

When it comes to DIETING, we talk about weight loss, but the real goal is fat loss.   When you lose weight, you can and do lose fat, but you can also lose muscle.

Muscle "disappearing"It’s a problem with any “weight loss” strategy, including conventional dieting, but this class of drugs seems to  AMPLIFY the problem. Head to head comparisons highlight the true extent of the problem.

So how much muscle loss are we talking about ?

Few studies have documented the extent of the muscle loss, one that did, suggested the muscle loss was in the order of 6 kg.

Comparison of level and time frame of weight loss Relatively speaking, this is A LOT.  You are losing muscle as you age, this loss clocks in at 1 – 3 kg per decade.   PER DECADE !

So 6 kg in 72 weeks is SIGNIFICANT!

Lost muscle brings frailty

And remember it’s this muscle loss that drives GETTING OLD and when enough muscle is GONE, you fall into the category of frail.  The medical terminology for this is sarcopenia (too little flesh).

When you’re frail : you’re vulnerable.

To falls, to infections, to EVERYTHING.

And low muscle mass is not just a problem for ninety two year olds, it is one of the first signs of metabolic troubles.  Read more here.

So the weight loss induced by the TITANS of weight loss is TAINTED.

So should you avoid them ?

This is biology – it depends.  You do  need to weigh up the pros and cons and  mitigate the risks.

Muscle loss is a thing,  FOR EVERYONE.

This is not a case of adverse event that happens because you are somehow genetically disadvantaged, it’s going to happen.

The extent of the loss is impacted by

  • genetics
  • age,
  • gender
  • metabolic status

Muscle mass is adaptable

Fortunately muscle can be “built” – with sweat and tears.  Okay, maybe the tears are optional, but the sweat isn’t.

To build muscle you need to WORK THEM.

The best way to work them is to make them LIFT/PUSH/PULL heavy things.   The official name for this kind of exercise is resistance training.  And research shows it does help mitigate the muscle loss.

Study tracking muscle loss when taking drug only, exercising only or combining drug and exercise

Effects of Liraglutide combined with exercise on body composition . The blue shows the drug on its own, the yellow the drug + exercise.  Mmmm, the green confirms exercise alone  has legs.© 2024 by the American Diabetes Association

Of course…….. this is HARD WORK, but exercise plus a weight loss titan trumps the drug on it’s own.

Mitigating the risk

A win  ?  You bet, but it does challenge the idea of EASY WEIGHT LOSS thanks to drug therapy. Lol.

Weight loss strategy que

I think creating BETTER BODY CHEMISTRY without drugs is a better option and it is more do-able than you might think, especially if you use biological principles. If this is an option you want to explore……. sign up for a day of Voxer, let me help you figured out where to begin.

Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body  Composition? Diabetes Care (2024) 47(10):1718–1730. João Carlos Locatelli, Juliene Gonçalves Costa, Andrew Haynes, Louise H Naylor, P Gerry Fegan, Bu B Yeap, Daniel J Green.

Further reading

paracetamol metabolites

Don’t let your pain medication put you in a wheelchair ?

When it comes to medications, what goes in, must come out, and it’s getting paracetamol “out”, that is it’s Achilles heal – putting you at risk of health problems

eating protein saves your muscles

Eating protein saves your muscles while the fat cells burn

You’ve decided to go on diet to lose some of those extra pounds. You plan to lose the fat, which is creating the somewhat unsightly belly tyre, but will you ?.

Mother Nature stealing from peter to pay paul

Are You Losing Muscle Without Realizing It?

You might be losing muscle without realizing it even when you’re trying to improve your health by hitting the gym and lifting heavy.

 

Want to discover more ways to create BETTER BODY CHEMISTRY ?

Posted in Obesity | Tagged exercise, GIP, GLP-1, glucagon, hyperinsulinemia, incretins, muscle, muscle loss, ozempic, sarcopenia, semaglutide, wegovy, weight loss drugs

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