Glp-1 agonists

[Merovinge]

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Eh, I disagree, personally. I think that lifestyle interventions should be a significant focus and that obesity is a major issue that is easier to interrupt in its earlier stages.

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00380-7/fulltext

Effective strategies for childhood obesity prevention via school based, family involved interventions: a critical review for the development of the Feel4Diabetes-study school based component - BMC Endocrine Disorders

Background Although there are many interventions targeting childhood obesity prevention, only few have demonstrated positive results. The current review aimed to gather and evaluate available school-based intervention studies with family involvement targeting dietary, physical activity and...

bmcendocrdisord.biomedcentral.com

Everybody agrees that lifestyle interventions done in a appropriate manner (e.g. focusing on less processed foods, less sugar intake, movement the child enjoys) is a good thing.

The disagreement points are on talking about weight exclusively as a marker of illness and how one would even broach discussing weight loss medication in a child who is just starting middle school without a concern other than weight. I strongly support adolescent metformin in teens with preDM or early DM, I even prescribe it personally to these kids, DM2 is no joke and we have to prescribe medications that raise the risk of this. That's entirely different than prescribing it solely for the purpose of weight loss, not only is it minimally effective at best, but the messaging is that your weight itself is the problem. We know the result of how this messaging effects kids (and adults), spoiler alert is they gain weight more often than lose and rates of ED increase.

 

[Mad Jack]

Everybody agrees that lifestyle interventions done in a appropriate manner (e.g. focusing on less processed foods, less sugar intake, movement the child enjoys) is a good thing.

The disagreement points are on talking about weight exclusively as a marker of illness and how one would even broach discussing weight loss medication in a child who is just starting middle school without a concern other than weight. I strongly support adolescent metformin in teens with preDM or early DM, I even prescribe it personally to these kids, DM2 is no joke and we have to prescribe medications that raise the risk of this. That's entirely different than prescribing it solely for the purpose of weight loss, not only is it minimally effective at best, but the messaging is that your weight itself is the problem. We know the result of how this messaging effects kids (and adults), spoiler alert is they gain weight more often than lose and rates of ED increase.

Oh I totally agree. Weight itself isn't a good indicator of anything, unless you're past a certain point. Honestly I don't think any kid should be on these meds unless they've got a very poor weight trajectory due to antipsychotic use or they're prediabetic/type 2 diabetic. Lifestyle interventions should be key for anyone, and we know they can be effective. Prevention, on the other hand, has never had good demonstrable benefit. I think if you've got a kid that is clearly struggling with weight, where it is impacting their self-esteem or their ability to engage in things their peers are doing, they should be offered lifestyle intervention. Medication, and particularly medication we don't know the long-term side-effects and consequences of in non-diabetic youth populations... That's extremely concerning and borderline disturbing to me, except in the most extreme of cases where there might be some role

A Review of Primary Care-Based Childhood Obesity Prevention and Treatment Interventions - PMC

Effective obesity prevention and treatment interventions targeting children and their families are needed to help curb the obesity epidemic. Pediatric primary care is a promising setting for these interventions, and a growing number of studies are ...

www.ncbi.nlm.nih.gov

 

[mistafab]

The tough thing with childhood obesity is you aren’t treating the child, you’re treating the family.

I rotated with a peds Endo md who saw predominantly childhood morbid obesity w/ T2DM. These folks are doing god’s work.

Imagine being that child at 300 lb age 12 getting told about processed foods, exercise… they go home and mom/dad are guzzling 2Ls of coke or sprite (each) and grab hot food for each meal (not to mention siblings). Such a tough thing to intervene on - we aren’t working in a vacuum here.

 

[whopper]

I got a patient, morbidly obese, so heavy my scale can't even weigh him. He's over 400 lbs. Guy's already been tried on pretty much everything minus ECT that he refuses. He's also already on a GLP-1 agonist.

I've noticed that in some morbidly obese patients they've been severely traumatized and have learned helplessness in addition to depression. Add to this they often times have a family member enabling the obesity. The bottom line is someone so obese and depressed usually can't afford to eat this much unless someone's paying for and preparing for this ungodly amount of food. Some documentaries have already brought up recurring trends in this type of morbidly obese person that match what I've seen.

He's now in what I bluntly told him-is what I believe will eventually be medical checkmate within several months. His obesity is now giving him osteoarthritis of the knees. I told him to do the life-chess calculations in his head. Then months from now he will walk less which in effect will make him gain more weight which in effect will cause more pain on his knees. Positive feedback loop leading to death within months to a few years. He refuses ECT. He has capacity to make decisions but won't take my strong recommendations to undergo extensive psychotherapy to treat his PTSD and learned-helplessness.

I've diagnosed him Eating Disorder NOS in addition to MDD and PTSD.

 

[VA Hopeful Dr]

I got a patient, morbidly obese, so heavy my scale can't even weigh him. He's over 400 lbs. Guy's already been tried on pretty much everything minus ECT that he refuses. He's also already on a GLP-1 agonist.

I've noticed that in some morbidly obese patients they've been severely traumatized and have learned helplessness in addition to depression. Add to this they often times have a family member enabling the obesity. The bottom line is someone so obese and depressed usually can't afford to eat this much unless someone's paying for and preparing for this ungodly amount of food. Some documentaries have already brought up recurring trends in this type of morbidly obese person that match what I've seen.

He's now in what I bluntly told him-is what I believe will eventually be medical checkmate within several months. His obesity is now giving him osteoarthritis of the knees. I told him to do the life-chess calculations in his head. Then months from now he will walk less which in effect will make him gain more weight which in effect will cause more pain on his knees. Positive feedback loop leading to death within months to a few years. He refuses ECT. He has capacity to make decisions but won't take my strong recommendations to undergo extensive psychotherapy to treat his PTSD and learned-helplessness.

I've diagnosed him Eating Disorder NOS in addition to MDD and PTSD.

Unless he has other medical issues that you didn't mention, I think you overestimate how dangerous obesity is in the short term.

 

[clausewitz2]

I got a patient, morbidly obese, so heavy my scale can't even weigh him. He's over 400 lbs. Guy's already been tried on pretty much everything minus ECT that he refuses. He's also already on a GLP-1 agonist.

I've noticed that in some morbidly obese patients they've been severely traumatized and have learned helplessness in addition to depression. Add to this they often times have a family member enabling the obesity. The bottom line is someone so obese and depressed usually can't afford to eat this much unless someone's paying for and preparing for this ungodly amount of food. Some documentaries have already brought up recurring trends in this type of morbidly obese person that match what I've seen.

He's now in what I bluntly told him-is what I believe will eventually be medical checkmate within several months. His obesity is now giving him osteoarthritis of the knees. I told him to do the life-chess calculations in his head. Then months from now he will walk less which in effect will make him gain more weight which in effect will cause more pain on his knees. Positive feedback loop leading to death within months to a few years. He refuses ECT. He has capacity to make decisions but won't take my strong recommendations to undergo extensive psychotherapy to treat his PTSD and learned-helplessness.

I've diagnosed him Eating Disorder NOS in addition to MDD and PTSD.

I have a patient who is very functional in most respects (healthcare professional) but is 350 lbs and is not a tall man to begin with. He's not afraid of physical activity, has a personal trainer and hits the gym regularly and all that, but family is a big part of this. He eats dinner with his parents multiple times per week and per his report it is a very classic Italian American red sauce kind of diet, i.e. heaping plates of pasta + bread for every meal.

He told me recently his mom always comments that he seems like he's gaining weight whenever he goes over. Couldn't help myself - "It strikes me that that's a bit rich, seems like she ought to take a bit of the blame for this."

At least I finally convinced him that sleeping 13 hours a night and being exhausted all the time was not really normal and he grudgingly agreed to get an HST. He has OSA, quelle surprise.

 

[whopper]

I've diagnosed him Eating Disorder NOS in addition to MDD and PTSD.

Forgot to mention....why I brought his case up in the first place.
I've had him see eating disorder specialists. They say he doesn't have an eating disorder. My point is that eating disorder providers are locked into an Anorexia/Bulimia/purging only are eating disorders mindset.

At least I finally convinced him that sleeping 13 hours a night and being exhausted all the time was not really normal and he grudgingly agreed to get an HST. He has OSA, quelle surprise.

We live in a country now where the majority is overweight. Despite this most patients I see with sleeping problems the prior doctor is simply giving Ambien and not even bringing OSA-despite the obvious-problems staying asleep, snoring, obese, and fat neck.

 

[mistafab]

... the obvious-problems staying asleep, snoring, obese, and fat neck.

I love to shock medical students when teaching them the STOP BANG score for OSA.

They say "why did you give them a point for the neck circumference? I didn't see you measure anything"

I say "look at my neck. My shirt size is 15.5" on the neck. Anything bigger than my neck is a positive for OSA risk." - which stop bang scores positive if >40 cm (~16 in or more).

You see them get a wave of realization how many people walk around with large necks, and how common OSA likely is. An obese man >age 50 with a large neck is already at moderate risk of OSA... without even asking them a single question.

 

[psycho-matic]

I think all of this is fine to speculate, but I want to see these hypotheses tested in an academic setting in a rigorous manner. I don't usually use anything off label unless there's some evidence to do so.

Looks like there are some pilot studies, but none with semaglutide.

Dulaglutide reduces binge episodes in type 2 diabetic patients with binge eating disorder: A pilot study - PubMed

Dulaglutide treatment reduces binge eating behaviour in T2D patients with BED.

pubmed.ncbi.nlm.nih.gov

A pilot randomized controlled trial of liraglutide 3.0 mg for binge eating disorder - PubMed

Participants in both groups reported reductions in OBEs, with the liraglutide group showing clinically meaningful weight loss. A pharmacy medication dispensing error was a significant limitation of this study. Further research on liraglutide and other GLP-1 agonists for BED is warranted.

pubmed.ncbi.nlm.nih.gov

Improvement in binge eating in non-diabetic obese individuals after 3 months of treatment with liraglutide – A pilot study

We examined the effects of liraglutide, a glucagon-like peptide-1 analogue on appetite and plasma ghrelin in non-diabetic obese participants with subc…

www.sciencedirect.com

And a review:

Would glucagon-like peptide-1 receptor agonists have efficacy in binge eating disorder and bulimia nervosa? A review of the current literature - PubMed

Binge eating, eating an abnormally large amount of food in a discrete period of time with a sense of loss of control over eating, is a defining feature of the eating disorders binge eating disorder (BED) and bulimia nervosa (BN). Both BED and BN are important public health problems for which...

pubmed.ncbi.nlm.nih.gov

That review says there are case reports of using it successfully in hyperphagia associated with Prader-Wili syndorme and those with hypothalamic obesity. I'd probably be more keen in using it in the intellectual disability, genetic abnormality patient population, especially those who are minimally verbal and can be aggressive due to their food cravings that I see as a CAP.

Another thing I wonder is about whether it would be useful for antipsychotic-induced weight gain when metformin and topiramate don't work.

There's good evidence to support use of melatonin in anti-psychotic induced metabolic syndrome. Worth adding to your armamentarium if you haven't tried it.

 

[Atreides]

There's good evidence to support use of melatonin in anti-psychotic induced metabolic syndrome. Worth adding to your armamentarium if you haven't tried it.

Wow, I thought this was a typo and you meant metformin. Ended up going down a PubMed rabbit hole. TIL

 

[psycho-matic]

Wow, I thought this was a typo and you meant metformin. Ended up going down a PubMed rabbit hole. TIL

The mechanism is certainly interesting.

 

[Ceke2002]

Very interesting discussion so far. I am more convinced by the arguments that these medications may be very helpful in binge eating than I am the arguments that they are unlikely to be abused by patients with restrictive type eating disorders. Patients with severe restrictive eating disorders are the furthest thing from rational and pursue illogical and dangerous means of weight loss/prevention of weight gain all the time. I'm not sure anything more than it being an available medication for weight loss matters on that level. And you can get dangerous physiologic sequelae of rapid weight loss while still at a normal or overweight bmi, so there are certainly patients with restrictive and purging eating behaviors who won't raise red flags to most physicians.

Speaking from my own experience with anorexia nervosa if a medication like the one being discussed had been available when I was actively engaged in my eating disorder, I absolutely would have tried to get some. As it was I tried to come up with all sorts of reasons why I should've been prescribed topirimate at the time (thankfully the drs I approached took one look at me and basically went, "lol, no!"). In my case my appetite was pretty messed up right from the start, as in I really didn't experience the physical sensation of hunger the way other people did, which did make restriction easier for me; however, that did not mean that me going so much as 50 calories over my daily allotted amount didn't send me into a complete tailspin of despair and panic attacks. If you'd told anorexic me, 15 plus years ago, that there was a medication that would help me eat only one meal a day, no snacking, I absolutely would've tried to jump on that. As you said we're not exactly known for our ability to think rationally when it comes to things like our weight or nutritional intake, heck at one point I was swallowing a hundred laxatives a day, do you really think I'm gonna baulk at taking a GLp-1 agonist? (rhetorical question)

Usual disclaimer - not a Doctor, not actual medical or peer reviewed advice, personal experience only and obviously I can't speak for any one but myself in this situation.

I think my concern is some of the testimonials I've read, where people have lost the weight they planned to lose, look like they're clearly in the range of <20 or so BMI, and state they want to stay on it forever and they only eat a meal a day. We may unintentionally be manufacturing anorexics through pharmaceutical means. Really wish I could find the couple of articles I'd read on this, if you swapped it ozempic for anorexia, they were basically describing many of the same desires, eating patterns, and weight trajectories. As someone who has worked on 3 eating disorder services over the years, it set off mega red flags.

One thing I've definitely noticed in many of the people with BED that I've gotten to know over the years, including my own mother, is that the majority don't really seem to want to just lose weight to a healthy level and adopt a healthier relationship with food. What they do seem to want is to swap one eating disorder for what they see as another, more desirable eating disorder.