Replies to post #247771 on Biotech Values

[Mufaso]

I look at all of the weight loss drugs that include a GLP-1 MOA as being necessary long term to keep the weight off. The simple theory is they work by suppressing appetite. If you go off them, you no longer suppress appetite and gain the weight back. Tolerability and whether you inject or not will be factors. IF you can tolerate an injectable "triple-g" (GLP-1, GIP and Glucagon) , you may use it to initially lose the weight and go on an oral to keep it off.

WRT Nash- yes there will be a need for long term drugs as well but I personally looking at the compounds containing GLP-1's as either maintenance or prevention. These compounds have shown little or no effect on fibrosis or inflammation although they do reduce liver fat which is thought to cause NASH in the the first place. So they may actually displace NASH drugs (e.g. ones from MDGL/AKRO/ENBT/VKTX) after NASH is resolved.

[DewDiligence]

Re: LLY’s Retatrutide safety

[Triple-agonist drugs such as LLY’s Retatrutide] might be okay for weight loss because many patients will only use the medications for a modest time period then come off once they have lost a target amount of weight.

I’m inclined to concur with Mufaso’s viewpoint in #msg-172230478 that weight-loss drugs will need to be taken chronically to maintain lost weight.

…I don't know if titration combined with antiemetics etc can address a good chunk of the GI tox.

They probably can to a degree; however, titration is unlikely to help with arrhythmia and other cardiovascular side effects such as long-QT (which was observed in one patient in LLY’s trial and was deemed to be drug-related).

[iwfal]

It might be okay for weight loss because many patients will only use the medications for a modest time period then come off once they have lost a target amount of weight

There is a reasonably strong rebound effect upon discontinuation, altho not all the way back to baseline (it seems to start asymptoting at perhaps, ~30% of best weight loss):

Lots of concern about #weight regain after stopping a med like #ozempic https://t.co/nT9sneLdJP

Great study cited by @people : https://t.co/jpQPGYo5tr shows what happened in STEP1 extension

Weight seems to go back to baseline. But not worse. There’s no excess rebound effect. pic.twitter.com/aIuoFjILeC

— Beverly G. Tchang, MD (@BevTchangMD) January 31, 2023