erictopol.substack.com
The latest on a glp-1 drug:
To me the biggest concern is that these companies appear to be promoting a lifelong duration of therapy, as evident by their zero attention to getting people off the drugs, without reverting back for both weight gain and risk of adverse outcomes. That is clearly unacceptable and major pressure is needed to get all companies making this class of drugs to test and validate durable and safe exit strategies.
Comments:
I’ve seen such elation in people finally losing 40-80 pounds who had struggled mightily before these game changers. I think as clinicians it is an imperative to develop best practices and consensus off ramps so these meds are not chronic meds for life for most people, although some will “need” them indefinitely. I have stopped bp meds, diabetes meds, pain meds in many patients after successful weight loss reverses conditions like hypertension diabetes etc, so there is sometimes a trade off between being on a Glp 1 agonist longer term, but being off 4-5 other meds because of the weight loss achieved.
Rarely have I participated in such a satisfying intervention for people, so I’m not going to cast too much shade on the pharma companies yet (novo, Lilly, etc).
But this has inspired me to do a formal post soon proposing some ways to taper off Glp 1 meds once weight loss goals have been achieved. Are you aware of any guidelines from medical organizations/authorities yet?
Avoiding an all or nothing approach with being on these meds seems prudent, with a stepwise leisurely taper down over whatever time works for the patient. Maybe in/off like we do for diuretics and chf based in monitoring vital signs/weight. Calorie counting and exercise to maintain success would be foundational principles I think.
Jeff Dobro
Very nice review of a significant study.
One comment on the cost though- the pharma companies are paying very large rebates back to the PBMs, some of which get shared back with the employers and CMS who are actually paying for these, so the actual cost of these drugs is not $1,000 - $1,600 per month.
No doubt that with the huge % of Americans that are obese (and the additional % that have a BMI >27), even 1/2 that cost per month is a huge economic burden.
The clinical findings are important and yes- the absolute reduction in significant outcomes is small.
What are the realistic interventions here?
Here are the questions running through my mind.
Over the course of a life, would bariatric surgery be more cost effective? Probably but what entity has the financial obligation for an individual over the course of their lifetime?
The long term adherence rate of lifestyle and diet attempts to lose weight are dismal. Although they need to be part of the answer, we know that they are not the complete answer.
Are the oral GLPs or triple hormone targeted drugs going to be more cost-effective than the current injectables? Probably not.
Could the oral drugs expand the actual user base so much that we can't afford these therapies at all? Probably.
Will cardiac, cancer and other obesity related consequences increase again in a pragmatic world once patients are off these meds? Evidence shows most gain their weight back but what happens to these co-morbidities?
How do we compare the costs of other lifelong branded drugs to these that have a similar benefit? It will be a long time before we have generics in these classes.
I don't have the answer but a multi-pronged approach including a glide path off these drugs seems like the best approach.
Tokyo Sex Whale
It’s hard to call the absolute risk reduction disappointing when in was the effect size that the trial was designed to detect: a 20% risk reduction in a high-risk population. It would have been one thing if the % risk reduction was less than expected but still statistically significant because the background event rate was even higher than expected. Or that a 20% reduction lacked statistical significance because the background rate was lower than anticipated. If achieving the results that the trial was designed to achieve is disappointing then they should have designed a smaller less expensive and, possibly, shorter trial powered to show an effect that justified the cost of the drug.
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