Zyprexa - Saxenda masking diabetes?

[jarn]

So I take 30mg of zyprexa, at night.  3mg of Saxenda to control the munchies and try and help the weight gain be mitigated.  I've been on zyprexa about a year.  I gained about 22lbs (was already obese), I've now lost 7.9lbs (whee!) since late January.  I am really focusing on eating well, in part, because my lipids aren't great, and that freaks me out.  

My pdoc says I'll just have to deal with the high lipids, that they're a side effect of the zyprexa, but it works well enough we haven't passed the bar that would mean I can be taken off of it.  I am not a fan of this, but I get he knows I've had violent thoughts pre-zyprexa, and most other APs either haven't worked or crapped out.

Could I have developed Type 2 diabetes from the zyprexa that the saxenda is masking?  At first I took metformin but holy upset stomach.  I had my last fasting glucose ages ago, but I have had two a1c tests more recently and everything's always been normal.  

 

[jarn]

Anyone?  I think @Iceberg @browri and @notloki are the smart med people?  I won't be surprised if this is more medical than medication.  I have googled to no avail.

[Iceberg]

It’s not unheard of to gain the weigh but still have reasonable blood sugar... it happened to me on zyprexa as well. If you had diabetes, I would think that your A1c would be higher... I believe (but am no endocrinologist) that once you contract type 2 diabetes your a1c tends to linger in the high range 

[jarn]

Thanks @Iceberg I was wondering if I'd have a high a1c if I stopped taking the Saxenda.  Realistically probably not.  I see my pdoc on March 10th and am struggling with not wanting to stay on zyprexa while knowing he'll be unwilling to take me off of it.  I have started to lose weight again, so I should probably give it a bit longer.  Ugh.  The lipids thing bothers me, and then I thought - oh god, what could this also be doing?

[Iceberg]

Yeah but (sorry for the preceding beating of a dead horse) you have to take into account what else your unchecked MI could be doing off the med 

[jarn]

Oh absolutely.  I was going to ask to go on another med...though I've been through most of them (I believe clozapine is next in line, and I can't imagine that'll be any better from a side effect profile) and zyprexa works the best any have worked in a long time.  

[yarnandcats]

i was on victoza (the lower dose sister of saxenda) for type 2 and weight control (along with metformin, funnily enough). it will bring your a1c into a more normal range, for sure. the only way, to my knowledge, to be properly assessed for type 2 is to stop any meds that will interfere with whatever testing is being done (a1c and/or glucose tolerance) beforehand. i also know that some AAPs can cause metabolic syndrome and high lipids are one sign of that but that those can be partly mitigated via diet/lifestyle (if i'm remembering right). if any of this is incorrect, just ignore; this is what my doc's have told me.

[Iceberg]

24 minutes ago, jarn said:

Oh absolutely.  I was going to ask to go on another med...though I've been through most of them (I believe clozapine is next in line, and I can't imagine that'll be any better from a side effect profile) and zyprexa works the best any have worked in a long time.  

I have actually had less weight issues with cloz than with zyprexa ... but it really is a commitment to get and stay on it 

[jarn]

Thanks @yarnandcats and @Iceberg

Yarn, the zyprexa is screwing with my lipids.  I'm trying to eat high fiber (easy) and low fat (hard).  I used to take Victoza for depression!  I will ask my pdoc about this too I guess.  It just freaks me out.  I'm also hoping if I eat healthy vegan food that will help.  I ate great yesterday until I had a big bag of chips, sigh.  I've always had binging issues - I wasn't hungry, just psychologically I do it.  

Iceberg, if I were going to go on clozapine, now's the time to do it as I'm working from home.  But I think the side effects on it would be bad too (even if weight isn't THAT bad).  

[browri]

On 2/22/2021 at 3:14 PM, jarn said:

So I take 30mg of zyprexa, at night.  3mg of Saxenda to control the munchies and try and help the weight gain be mitigated.  I've been on zyprexa about a year.  I gained about 22lbs (was already obese), I've now lost 7.9lbs (whee!) since late January.  I am really focusing on eating well, in part, because my lipids aren't great, and that freaks me out.  

My pdoc says I'll just have to deal with the high lipids, that they're a side effect of the zyprexa, but it works well enough we haven't passed the bar that would mean I can be taken off of it.  I am not a fan of this, but I get he knows I've had violent thoughts pre-zyprexa, and most other APs either haven't worked or crapped out.

Could I have developed Type 2 diabetes from the zyprexa that the saxenda is masking?  At first I took metformin but holy upset stomach.  I had my last fasting glucose ages ago, but I have had two a1c tests more recently and everything's always been normal.  

 

There are a few difficult things to unravel here. The first part is that Zyprexa is a dopamine antagonist. With reduced dopamine activity comes increases in prolactin which can cause dyslipidemia, increase blood sugar, general metabolic dysfunction, etc. Second part is that Zyprexa is a strong muscarinic acetylcholine receptor antagonist, particularly M3 which is found on pancreatic cells. Its antagonism correlates positively with type 2 diabetes. Even plain anticholinergics like Cogentin (benztropine) carry a high risk of type 2 diabetes when used on a regular basis. Zyprexa is also a strong adrenergic blocker which can cause glycemic dysfunction as well. There are multiple different ways that Zyprexa can cause type 2 diabetes. More ways than most atypicals except maybe clozapine.

Saxenda adds an interesting component to the mix. It works by increasing the conversion of glycogen stored in fat into glucose. So GLP-1 agonists like Saxenda/Victoza (liraglutide), Ozempic/Rybelsus (semaglutide), and Trulicity (dulaglutide) will all contribute to increases in glucose even if they improve HbA1c. This would be particularly pronounced if you are overweight and there's lots of glycogen to convert. However, combined with diet and exercise, the increases in glucose should be marginal, and these medications do in fact have effects in the brain to affect a feeling of satiety.

At a dose of 30mg Zyprexa, it is reasonable to suspect that in the long run you may develop type 2 diabetes. That's just statistics really. And that's why Eli Lilly got sued over it. The new guidelines from RANZCP (Australia and New Zealand's equivalent of the American Psychiatric Association) actually have minimized the use of olanzapine to the point that it's not even first-line anymore. Other options are supposed to be tried first and they have basically indicated that there is no space for Zyprexa to be used as maintenance treatment anymore because of the safety issues and newer options being available. It's probably difficult for the world of psychiatry because Zyprexa is a really effective medication but it's hamstrung by its risks.

[jarn]

Thanks @browri - I really appreciate it.  I've been through most AAPs and a couple of APs, this was one thing to try before clozapine.  

I showed your response to my husband and he is supportive of me asking to go off of zyprexa - I was thinking of trying Abilify again.  If I lose weight that will help my mood too.

Plus, it's not clear how well zyprexa is working - I've had mood issues off and on.  And in the last week I've had bad anxiety, a day of mild depression, and suicidal thoughts (I'm not suicidal - but me/not me voice tells me stuff like I could drown myself, and to 'do it now').  I see him next Thursday now.

[Iceberg]

On 2/25/2021 at 9:13 AM, jarn said:

Thanks @yarnandcats and @Iceberg

Yarn, the zyprexa is screwing with my lipids.  I'm trying to eat high fiber (easy) and low fat (hard).  I used to take Victoza for depression!  I will ask my pdoc about this too I guess.  It just freaks me out.  I'm also hoping if I eat healthy vegan food that will help.  I ate great yesterday until I had a big bag of chips, sigh.  I've always had binging issues - I wasn't hungry, just psychologically I do it.  

Iceberg, if I were going to go on clozapine, now's the time to do it as I'm working from home.  But I think the side effects on it would be bad too (even if weight isn't THAT bad).  

The issue you might run into is the blood tests... I don’t mind getting blood taken at all, but I’ve found the logistics of all the required tests can be a massive pain in the ass. For what it’s worth, cloz did work infinitely better than zyprexa for me 

[browri]

3 hours ago, jarn said:

Thanks @browri - I really appreciate it.  I've been through most AAPs and a couple of APs, this was one thing to try before clozapine.  

I showed your response to my husband and he is supportive of me asking to go off of zyprexa - I was thinking of trying Abilify again.  If I lose weight that will help my mood too.

Plus, it's not clear how well zyprexa is working - I've had mood issues off and on.  And in the last week I've had bad anxiety, a day of mild depression, and suicidal thoughts (I'm not suicidal - but me/not me voice tells me stuff like I could drown myself, and to 'do it now').  I see him next Thursday now.

I'm not saying Zyprexa is the devil's drug. It has its place, and in doses of 2.5mg to 5mg, it can make a nice sedative and can help mood during the day. Yet, it carries such significant metabolic risks that taking 30mg damn well better bring you to near complete remission for all the problems it can cause, and if it doesn't, then it probably isn't worth it.

[Iceberg]

Jarn- another option some people use is reducing the dose a bit and adding something like abilify to reduce overall side effect profile while still having coverage. Don’t think that’s necessary for you right now but thought I’d mention it 

[jarn]

Thanks @browri and @Iceberg.  Pdoc's goal for me was always to be at 20mg, but it got raised a few times.  The dosage freaks me out given what it's doing to my lipids.  I feel gross and unhealthy now.  

Pdoc seems very set on me staying on zyprexa though.  I'm going to have to be persuasive.

[browri]

Then I would say to trust your doctor. Remember, it's one thing to look at the pharmacology of it all and get really focused on the bad it can cause. It's another thing for it to be a reality. Your lipids may be off, but you said your fasting glucose and HbA1c were normal. So I would say to not let it distress you. If you're taking Zyprexa, a general metabolic panel should be taken regularly, but that would already be happening because you're taking Saxenda. Someone has an eye on your numbers and will flag them if there's a problem. And I'm sure that your pdoc is aware of Zyprexa's risks and finds them to be acceptable in your case given your glucose and A1c.

Have you considered talking with your gdoc about starting a lipid-lowering agent? It's not unusual for Zyprexa patients to take fenofibrate or a statin with or without metformin as a preventative measure.

[jarn]

7 minutes ago, browri said:

Then I would say to trust your doctor. Remember, it's one thing to look at the pharmacology of it all and get really focused on the bad it can cause. It's another thing for it to be a reality. Your lipids may be off, but you said your fasting glucose and HbA1c were normal. So I would say to not let it distress you. If you're taking Zyprexa, a general metabolic panel should be taken regularly, but that would already be happening because you're taking Saxenda. Someone has an eye on your numbers and will flag them if there's a problem. And I'm sure that your pdoc is aware of Zyprexa's risks and finds them to be acceptable in your case given your glucose and A1c.

Have you considered talking with your gdoc about starting a lipid-lowering agent? It's not unusual for Zyprexa patients to take fenofibrate or a statin with or without metformin as a preventative measure.

I guess I'm scared that the Saxenda is masking diabetes.  It really freaks me out.  I'll talk to pdoc.  

I told gdoc I wanted to try to eat a high-fiber, low-fat diet and therapeutically fast.  I've had mixed luck with that.  High fiber is super easy - I can get 200% of the RDI no problem - but low-fat is tough.  And fasting goes so-so.  I need to apply myself better.

[browri]

19 hours ago, jarn said:

I guess I'm scared that the Saxenda is masking diabetes.  It really freaks me out.  I'll talk to pdoc.  

I told gdoc I wanted to try to eat a high-fiber, low-fat diet and therapeutically fast.  I've had mixed luck with that.  High fiber is super easy - I can get 200% of the RDI no problem - but low-fat is tough.  And fasting goes so-so.  I need to apply myself better.

Is going off the Saxenda temporarily an option to determine if there is underlying T2DM? Perhaps finding out for sure may help to ease your worry. It could, on the other hand, reveal a problem. In which case, hopefully your gdoc and pdoc recognize this and make a correction.

Like I said in a previous post though, Zyprexa is still used in tandem with other medications to either prevent or correct metabolic dysfunction from Zyprexa. My partner takes Risperdal and has experienced metabolic dysfunction and weight gain since starting it. He has also started Saxenda 3mg and also takes 145mg of fenofibrate to lower his triglycerides, which were the serious issue. Saxenda has also helped him immensely with appetite satiety issues.

[jarn]

Thanks @browri - I am concerned about a lack of appetite control going off of Saxenda.  I went on Metformin the third day on zyprexa because I was eating EVERYTHING.  I went to bed hungry, woke up hungry, spent the day hungry...

I AM going to push back my blood test to recheck lipids, as I have been stress eating since I started getting the voice (mine/the bossy guy) telling me to kill myself.  I talk to pdoc this Thursday now.