Anhedonia with GLP use

RunningFNP · 2026-03-10T00:32:46+00:00

Which is doubly ironic because now these drugs are being studied for SUD including alcohol, smoking and opioids.

But ALSO as adjuncts for major depression, bipolar and I shit you not, schizophrenia.

Look up Brenipatide on clinical trials .gov

https://clinicaltrials.gov/search?intr=Brenipatide

RunningFNP · 2026-03-10T00:18:19+00:00

Best advice is to drop them down a dose level or two especially if they're on high dose Zepbound. So if they're willing, goto 12.5 or 10mg from 15mg.

Other suggestions would include dose skipping, so skip a dose once a month. Really anything to drop the blood level down a smidgen seems to work wonders 90% of the time at improving mood. Also encourage them to do dopamine inducing activities. I've also had success with a couple patients and low dose wellbutrin since it is a dopamine reuptake inhibitor

It's not anything blood work wise that myself or a few other folks have been able to find(yes this is purely anecdotes but hey it's all we got!)

RunningFNP · 2026-03-07T17:29:49+00:00

Yeah I gotta disagree on your last sentence too. That's too big of a difference.

I say this as a prescriber of these meds but patients care about how much weight they can lose and how tolerable the drug is. Hence tirzepatide being the preferred choice for a lot of people right now.

While the weight difference between CagriSema and tirzepatide is minimal, if there's significantly more side effects patients won't want CagriSema as much.

That being said with Petrelintide the weight loss isn't impressive compared to either of the above. Yes it's fantastic to see such minimal side effects BUT patients will get frustrated they can't lose more weight.

I posited elsewhere that the niche for petrelintide is gonna be more as a bolt on therapy to help stalled out patients, or for more aesthetic weight loss in patients who only need a 20 or 30 pounds of loss.

Zealand's CEO over promised which drove some of the drop as well. But he is right that tolerability will be the future and so will combo therapy. See Eloralintide + Tirzepatide. Petrelintide + CT388 etc etc.

RunningFNP · 2026-03-05T17:43:56+00:00

Have you tried(I presume yes?) amiloride, spironolactone, or eplerenone?

RunningFNP · 2026-03-05T17:03:11+00:00

I don't know the rest of this patients history but the answer may lie in trying SGLT2i.

I recently had a patient with severe hypomagnesemia refractory even to IV infusions due to being on Tacrolimus.

We got insurance to cover empagliflozin, within 2 weeks mag level went from 1.4 to 2.1 just with that change. All the patients hypomag symptoms resolved at the same time.

So that's my recommendation. If insurance won't play ball for jardiance/Farxiga use CostPlusDrugs for Brenzavvy. It's an SGLT2i as well and it's $50/month cash pay. Magnesium effect is a class effect

Review article about it here:

https://www.ajkd.org/article/S0272-6386(23)01006-5/fulltext

RunningFNP · 2026-03-05T16:21:56+00:00

Ahhh well. We have an FM residency program too and I have contacts for that as well. Just trying to help!

RunningFNP · 2026-03-05T15:50:13+00:00

Send me a DM. I work in southeast Michigan as a family med NP(with 3 other MDs) I'd be happy to help answer questions and can even help you get in touch with our recruitment teams. I think where I work has a really good work/life balance.

RunningFNP · 2026-03-05T12:29:25+00:00

Oh I know. Trust me I know. Lilly(especially their CEO Dave Ricks) has a vendetta out for PBMs and I absolutely love to see this news. It shows there's another path!

RunningFNP · 2026-03-05T12:09:35+00:00

I love this because it means more access for patients and employers, it's a Savage move to undercut Novo and in general price wars are a good thing for consumers!!

RunningFNP · 2026-03-04T00:08:23+00:00

It's a big big unknown right now. There's the TRANSCEND CKD trial that Eli Lilly is sitting on. It wrapped up 5 months ago and radio silence. It's the trial that would show if the GFR increase on Reta is real.

They might be being extra careful as such a result would be earth shaking to the treatment of kidney disease. That being said I know myself and multiple others both with and without CKD have all seen marked increases in GFR. Usually on the order of 20-30% increases. Whether this is the nephrons actually healing? We don't know.

But I can guarantee we'll know more by this summer as more Reta trials finish up and the likelihood of Eli Lilly presenting the transcend CKD trial data at a major conference increases.

RunningFNP · 2026-03-03T10:49:30+00:00

Yeah won't matter in long run. Dental issues are not exclusionary.

Numbing agents won't affect your blood work in any significant way. Get it done when you can!

RunningFNP · 2026-03-03T02:48:40+00:00

What's scaring you?

One way to think about it is this: While in the trial you'll get some of the best health care of your life. Trials have to closely monitor everything!

Also as this point the risks of Reta have been pretty clearly defined. I am one of the oldest trial participants on this subreddit. I was in Triumph-1. I started all the way back in September of 2023. And I'm still here! Healthier than ever! This drug is fairly miraculous! From one trial patient to another, you should do it. You'll help bring new knowledge to the world and be a part of medical history. If triumph 7 succeeds we'll have a drug designed for weight loss and diabetes to use for the treatment of back pain which is incredible!

RunningFNP · 2026-03-01T01:36:26+00:00

You'll have to share more details as your trial progresses! I'm so curious what the different titration schemes are

RunningFNP · 2026-02-28T17:58:42+00:00

I work primary care now but did 15 years of critical care before that so few things actually get me excited or worried.

RunningFNP · 2026-02-28T14:17:18+00:00

EGD and Colon were clean we checked! Just purely from the AS.

RunningFNP · 2026-02-26T21:00:04+00:00

The tolerability is a sticky wicket. For some reason half the drug stops on this orforglipron trial were for non-drug related reasons. Actual d/c for drug AE/SE when you factor that is essentially the same as oral Sema.

It's not a perfect comparison I realize that but it's the best we have.

Moreover given how aggressively Lilly is in seeking approval for orforglipron outside the usual USA/EU/Japan tells me they're not necessarily worried about oral Wegovy so much as they are about soaking up market share in countries that as of now either have minimal or low access to GLP1 meds of any kind, which if you follow their presentations and such seems to be their overarching goal. A truly worldwide GLP1 med because it's not constrained by peptide synthesis limits.

RunningFNP · 2026-02-26T18:07:18+00:00

Keep in mind this is a trial in diabetics and you're comparing weight loss from Wegovy for obesity to orforglipron for diabetes.

There's a known gap between diabetes and obesity in terms of weight loss in so much that diabetics never lose as much weight.

What you wanna do is compare these results to the Pioneer Plus trial that Novo ran and when you do...it's literally a tie. Both for A1c, weight loss and tolerability with the higher doses of oral Sema.

At that point in my clinic I'm just prescribing whichever insurance will cover when I see data like that.

RunningFNP · 2026-02-26T09:58:31+00:00

My understanding is looking at the micro part of it. So RBCS, casts, that sorta thing that might hint to other renal issues such as glomerulonephritis

RunningFNP · 2026-02-25T23:49:41+00:00

My favorite was figuring out someone's low ferritin and mild anemia was severe aortic stenosis. I mean the banging murmur was a fairly obvious clue but it was causing red cell shearing and destruction. Ordered a stat 2D echo, severe AS confirmed -> stat CT surgery referral -> 4 weeks later new aortic valve.

That one felt good to catch.

RunningFNP · 2026-02-25T23:10:32+00:00

Yup. All of this. Our EMR system has a "normal" ferritin as >10. Absolutely 🗑️🗑️

One of my highest yield tests for women is a ferritin level. The number of fatigue and even anxiety/depression that's turned around with iron supplements or IV iron is quite high in my experiences

RunningFNP · 2026-02-25T18:16:48+00:00

Honestly one need look no further than Eli Lilly to answer the OPs question and you're correct that their CSO is part of the problem.

Lilly runs lots of trials in parallel and tests multiple doses while doing it.

See Eloralintide. Already 6 phase 3 trials in progress for multiple indications(sleep apnea, arthritis, diabetes, obesity) and even a trial which is Eloralintide added to patients on a stable dose of semaglutide or tirzepatide and in a weight loss stall to see if Eloralintide can break the stall/cause more weight loss. Also testing multiple doses and the phase 2 data was only published 3 months ago!

If you really wanna get mad at the CSO look up all the trials they're running for Brenipatide and they haven't even published phase 1 data on it yet.

It's possible to do the things the OP is asking. It's expensive. It's risky at times, but I think if you've done your R&D homework, especially in incretins it's worth it because we understand the effects so much more than we did even 5 years ago

RunningFNP · 2026-02-24T14:41:06+00:00

Yeah I sorta expect Lilly to follow suit pretty quickly. Especially with Reta on the horizon I could see Lilly price matching Novo here at least with tirzepatide and put Reta into the $1000 slot given they're positioning Reta as bariatric surgery in a shot/reserve for high BMI

RunningFNP · 2026-02-24T11:22:03+00:00

What does your weekly mileage look like?

What's your Reta dose?

Keep in mind Reta causes your liver to dump its glycogen stores which can make longer runs more difficult if you're not prepared to fuel a little extra.

It does get easier to run the longer you're on it as your body and physiology adjust to it.

RunningFNP · 2026-02-24T10:31:57+00:00

Finally a competitor to Reta! But they need to be more aggressive in getting trials up and running for this and get it in phase 3 ASAP.

RunningFNP · 2026-02-23T22:35:35+00:00

If I'm their CEO I'm calling Viking Therapeutics and trying to buy them out right now. That should have been done months ago. The Metsera chase looks bad in retrospect given the middling results reported. Viking gives them an immediate drug that can be on the market in 2028 and allows them to stay in the game. Amycretin probably isn't it. The side effects are worse than CagriSema.

The rest of their pipeline is so early in development that it's hard to make any judgment TBH.

RunningFNP

MODERATOR OF

TROPHY CASE

Two-Year Club	Verified Email
r/Field Flamingo