Why would anybody consider taking this T2 medication

[~Noodles~]

Wow, I'm really surprised to read such a damning perspective on GLP-1 analogues, more especially so on a diabetes forum. They've become a staple of T2D treatment in recent years due to their effectiveness and apparently low side effect profile. The "only" new thing is oral delivery (quite a pharmaceutical feat really), making it easier on people afraid of needles for whatever reason.

Mind you, the only thing coming close to pharmaceutical greed is the energy regulating bodies put into denying us medicine for all kinds of far-fetched reasons. And all you need is someone stubbing their toe during trials and stubbing your toe will become one of the possible side effects. Have a look at the side effects of OTC pain relievers, we're lucky they've been around for eons, otherwise we'd need a presciption for Tylenol.

Dulaglutide was one of the first things I told my doc to put on a script instead of really damaging meds like sulfonylureas—I still can't believe those are still in use and the only reason nobody cares to touch them is probably their price.

Like countless other diabetics, I've been on dulaglutide for a few months now and the only effects I noticed were better control of my BG and a profound lack of hunger, which has helped me tremendously in losing weight.

 

[LittleGreyCat]

Wow, I'm really surprised to read such a damning perspective on GLP-1 analogues, more especially so on a diabetes forum. <snip>

The thing that concerned me when I looked into this was that on the NICE pathway (which admittedly tends to be out of date) the use of GLP-1 analogues was well down the treatment pathway and with all kinds of reasons to stop treatment after 3 months.

The up front specification looked good - insulin production up, glucagon production down, protection and possible regeneration of Beta cells - but the more I looked the more caveats I found.

I'm currently trying to work out how to get some expert advice on this.
Probably require a private consultation.

 

[Member496333]

I was listening to a podcast today and the guest posited that the optimal metabolic state in healthy humans is actually insulin down and glucagon up. The notion is that insulin high is dealing with excess exogenous carbohydrate, whereas glucagon up is creating just the right amount of endogenous carbohydrate to makeup the shortfall. Ergo flatline glucose and low insulin = optimal.

Obviously there are nuances (and many other factors) at play, particularly in those who are already metabolically broken, but nonetheless it seems logical that this should be the target for optimal homeostasis. Instead of cranking up the insulin in order to deal with excess carbohydrate, glucagon is ensuring a steady drip feed from the liver.

EDIT: I think it was Ben Bikman on the Low carb MD Podcast #58 (the guy is no fool)

 

[~Noodles~]

The thing that concerned me when I looked into this was that on the NICE pathway (which admittedly tends to be out of date) the use of GLP-1 analogues was well down the treatment pathway and with all kinds of reasons to stop treatment after 3 months.

The up front specification looked good - insulin production up, glucagon production down, protection and possible regeneration of Beta cells - but the more I looked the more caveats I found.

I'm currently trying to work out how to get some expert advice on this.
Probably require a private consultation.

Well I reckon it's all about liability. Nobody wants to sit down at the court house on the wrong seat when something goes south and as soon as there's a far out potential for harm use is limited to short time and a gazillion warning stickers are tacked on, just to be on the safe side. Now I'm all for safety but it's approaching cringeworthiness at times. In some cases we're letting people die because potential treatment hasn't undergone another umpteenth studies.

Yes, some people ended up with an inflamed pancreas using GLP-1 analogues. And others died because they used aspirin, crossed the street or got up in the morning. That's life.

And honestly, I think most docs spend less thought on meds than we do on this forum. They got some flyer, talked to a pharma rep and quickly browsed a study or two in a journal before they went off to the golf course. Chances are aunt Google tops whatever advice you can get out of a licenced expert. Those thoughts are my own and of course I highly recommend asking such experts for liability reasons.

 

[LittleGreyCat]

I was listening to a podcast today and the guest posited that the optimal metabolic state in healthy humans is actually insulin down and glucagon up. The notion is that insulin high is dealing with excess exogenous carbohydrate, whereas glucagon up is creating just the right amount of endogenous carbohydrate to makeup the shortfall. Ergo flatline glucose and low insulin = optimal.

Obviously there are nuances (and many other factors) at play, particularly in those who are already metabolically broken, but nonetheless it seems logical that this should be the target for optimal homeostasis. Instead of cranking up the insulin in order to deal with excess carbohydrate, glucagon is ensuring a steady drip feed from the liver.

EDIT: I think it was Ben Bikman on the Low carb MD Podcast #58 (the guy is no fool)

If your control is broken, then the usual rules may not apply (as you noted).

My specific issue is extended dawn phenomenon, where BG keeps on rising until about noon, then drops sharply to normal. Eating/not eating, exercise/not exercise doesn't seem to make much difference.

One explanation is over production of glucagon.

Hmm...checking Wikipedia as I write this and wondering.
https://en.wikipedia.org/wiki/Glucagon

Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It works to raise the concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body.[3] It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers the extracellular glucose.[4] It is produced from proglucagon, encoded by the GCG gene.

The pancreas releases glucagon when the concentration of insulin (and indirectly glucose) in the bloodstream falls too low. Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream.[5] High blood-glucose levels, on the other hand, stimulate the release of insulin. Insulin allows glucose to be taken up and used by insulin-dependent tissues. Thus, glucagon and insulin are part of a feedback system that keeps blood glucose levels stable. Glucagon increases energy expenditure and is elevated under conditions of stress.[6] Glucagon belongs to the secretin family of hormones.

My emphasis.

The bit that just confused me is "The pancreas releases glucagon when the concentration of insulin (and indirectly glucose) in the bloodstream falls too low. "

I thought that it was released when BG was low and insulin was high. That extract doesn't seem to make sense.
Unless glucagon does not suppress insulin production at all (which I thought it did, but can't find in the Wikipedia article).

So, if it is independent, then insulin production falls as BG falls and both drop together.
When BG falls too far then glucagon is released to push glucose (amongst other things) out of the liver and get BG to rise.
When BG rises then insulin production is stimulated.
I assume that rising BG also suppresses glucagon production.

So I'm now reviewing what I thought I understood.

Are insulin and glucagon completely independent, and the common factor in their production is stimulation by BG levels?

Either way, it looks as though my problem may be too much glucagon causing glycogenolysis (release of glucose from the liver) and gluconeogenesis (production of glucose from protein/fats).
I assume that if my BG is up, then the release of further glucose into the bloodstream is a mistake.
If that is combined with the slow initial release of insulin then this could perhaps explain extended DP.

{retires holding head in hands}

 

[Bwel]

If your control is broken, then the usual rules may not apply (as you noted).

My specific issue is extended dawn phenomenon, where BG keeps on rising until about noon, then drops sharply to normal. Eating/not eating, exercise/not exercise doesn't seem to make much difference.

One explanation is over production of glucagon.

Hmm...checking Wikipedia as I write this and wondering.
https://en.wikipedia.org/wiki/Glucagon


My emphasis.

The bit that just confused me is "The pancreas releases glucagon when the concentration of insulin (and indirectly glucose) in the bloodstream falls too low. "

I thought that it was released when BG was low and insulin was high. That extract doesn't seem to make sense.
Unless glucagon does not suppress insulin production at all (which I thought it did, but can't find in the Wikipedia article).

So, if it is independent, then insulin production falls as BG falls and both drop together.
When BG falls too far then glucagon is released to push glucose (amongst other things) out of the liver and get BG to rise.
When BG rises then insulin production is stimulated.
I assume that rising BG also suppresses glucagon production.

So I'm now reviewing what I thought I understood.

Are insulin and glucagon completely independent, and the common factor in their production is stimulation by BG levels?

Either way, it looks as though my problem may be too much glucagon causing glycogenolysis (release of glucose from the liver) and gluconeogenesis (production of glucose from protein/fats).
I assume that if my BG is up, then the release of further glucose into the bloodstream is a mistake.
If that is combined with the slow initial release of insulin then this could perhaps explain extended DP.

{retires holding head in hands}

Hi there,

I have a similar problem (@LittleGreyCat ), Rasied BG from ~3am through to the afternoon.
I've been LCHF for a year or so.
My last Fasting results are:
- Fasting Insulin is very low (1.8 mIU/L)
- Fasting C-Peptide - 0.45 ug/l
- Fasting Blood Glucose at same time of above - 9.5 mmol/L
- Fasting Glucagon is very high 248 ng/l

Last HOMA-IR = 0.8

It seems I'm struggling to produce Insulin, yet have Gloucagon / Gluconeogenosis in overdrive and have insulated BG for half the day.

Whilst I am on Insulin (2 x 6 units Basal), I am also taking some bolus albeit low doses becuase of minimal Carbs. This is just to try and keep my BG's somewhat lower.
I'm not considering starting Rybelsus, to see if this helps raise my low Insulin production and downregukate my high Glucagon levels.

@LittleGreyCat - could you update on what you did since last year ?

Many thx,

 

[LittleGreyCat]

@LittleGreyCat - could you update on what you did since last year ?

I was planning to try and get a private consultation to discuss the issues, and having trouble sorting out a consultancy referral, but then Covid happened.

My control has wandered during the first 6 months of Covid (some "eat, drink and be merry for tomorrow we die") but I am back fully on LCHF and am very low carb at the moment.
I never wandered totally away from LCHF but just had a few "treats" from time to time.

I still have the extended DP but with almost zero carbs the line has very much flattened out.

So I am in a holding pattern.

I am intrigued, though, by your very high glucagon levels.
This is what I suspected might be happening to me, as discussed up thread.
Also as discussed, in theory this should not be happening.
Then again our BG control is already broken; perhaps it is just broken in more ways than we expected.

Are you UK based?
If so, do you get your insulin, c-peptide and glucagon levels tested on the NHS?