Gary Taubes's argument that GLP-1 inhibitors work through fuel (re)partitioning

(Bob M) #1

In short, he thinks the GLP-1 inhibitors are allowing the body to access the calories stored in fat, and this is what causes people to (want to) eat less.

There’s an interesting mouse study of genetically altered mice (so called “transgenic” mice) where some took a drug and some did not, but they kept the calorie intake the same for both groups. Even though EATING THE SAME CALORIES, the mice taking the drug lost more weight. Why? Gary theorizes it’s because the drug provided access to the calories stored in fat, whereas the other mice could not access those calories.

As an aside, I think this is why some people can lose X pounds quickly (say X = 100 pounds), while it takes others a very long to never time to lose that weight. I think the latter have broken something that prevents the body from accessing the fat in the fat cells. I think hormones have a lot to do with this, including “insulin resistance” (by the hormone insulin), but this could vary a lot by person. For instance, menopausal women aren’t the same as men as far as hormones are concerned. I have no proof for this, other than it makes logical sense to me.

#2

I feel that’s just a rewording of what we already know of how GLP-1’s work. Once you’re on a GLP-1, you’re insulin sensitive, you’ll release more insulin when it’s needed because you’ll be receptive to that queue, because of that your blood sugar is only elevated long enough to do the job and not stay high longer than that, which means your blood sugar elevations (time wise) are minimal, and when that’s the case you can get a fat more often than when it’s chromincally elevated.

Me without Semaglutide will have an idle glucose level in the 105-115 range. I doin’t usually spike nuless I’ve been getting crappy sleep, which shows huge, A1C is usually low 5’s either way, but ith it, it’s usually in the high 80’s - low 90’s. With it I was able to get my BF% from the high 10’s to 9.2% at last check, eating in a surplus again now but going to try to hit the high 8’s next time. That definitely wouldn’t have happened without it.

Keep in mind that’s doing TKD/CKD!

I don’t pay retail gouge rate for it like most so long term isn’t an issue, but also have no intentions of it being a life thing either.

(Denise) #3

This topic interested me because since I had a hospital stay (pancreatitus never had before) of Tues-Saturday a couple weeks back, I have struggled to keep my BG down. I have a daily record, plus I know my numbers in hospital were high because they didn’t feed me my same keto diet, which I already knew that would happen.

I don’t have any problem with sticking to my Keto foods, (40% Protein, 50% Fat, 10% carbs or less)

I just read what Semaglutide is and even on my keto diet, my BG HbA1’c have still stayed in the 6.1 Pre-diabetes numbers. Can I ask why you do the Sema. injection? My BG’s are so crazy right now, it scares me. I keep thinking I’ll get back to more lower daily test-from-home, but they are still fluctuating after 2 weeks of being back on Keto :frowning:

I’m also rather disheartened because there is hardly any sort of studies (at least I can find) on Seniors like myself late 60’s to 70’s. I suspect there just aren’t many of us seeking better health :frowning: Like I think I have become invisible, heard that line in a movie/show.

(carl) #4

I was on Ozempic at low doses for a while, and got off of it because of what I was reading about it. Since then I have been using Allulose in my pre-meal and during-meal beverages, and I have noticed the same effects as when I was taking Ozempic. I am losing weight faster than before and am eating less. Then I hear about this study from 2018 https://pubmed.ncbi.nlm.nih.gov/29317623/ as summed up by this YouTube video https://www.youtube.com/watch?v=ZY2vU9I5uic. Good news for those who want the effects on the GLP-1 enablers at a much more affordable (and more delicious) price.

(Bob M) #5

@carl There was a podcast with multiple experts (Bikman, Dom D’Agostino, Volek, and others), and they really liked allulose. I tried allulose for a time for a drink at lunch, and I did think it worked. It seemed to take a while, though (eg, a few hours) to get to the full effect. Unfortunately, I was and am taking too much to figure out the effect from only allulose. I do use allulose at night sometimes, in a yogurt primarily. But then I can’t tell what effect it has. Other than at “lunch” (my first meal of the day), I haven’t tried it at other meals. It’s a good idea, though, as allulose is also supposed to lower blood sugar.

@lfod14 and @Goldengirl52 My initial concern about lowered blood sugar is because that might be due to higher insulin levels. I’ve been thinking higher insulin = bad for a long time.

However, the effects of these GLP-1 agonists are so complex, it’s hard to tell what’s happening. Check out this paper, for instance:

https://www.sciencedirect.com/science/article/pii/S2214750025000137

It’s hard to figure out what these drugs are doing.

Both my wife and daughter are taking one of these. They are definitely less hungry, though neither takes blood sugar, so I don’t know what’s going on there.

(Denise) #6

Glad I got alerted to this @ctviggen as it Interested me as I had given up on testing for awhile, and now I seem to have hit a good place for my glucose when I started just periodic fasting tests. I had to quit the popcorn, again, as it’s the only thing the gave me high numbers in the a.m. I think my body may be so used to such low carbs, when I started with the popcorn, and just a few more carbs like blueberries, nuts, seeds, yogurt, only 2 g of carbs per serving, anyway, just added up be was still low according the Keto “allowed”, and even what some recommend a lot higher amount for T2’s like myself.

They don’t work well, so now I am way down on my carbs again, and doing better. I still think there are other reasons, and I’ll keep trying to figure things out. Insulin Resistance yes, I read somewhere that can still be going on in my body, although I don’t know how to check that for sure. I just figure the more I lean towards Carnivore the better I feel (sleep, lack of any hunger pangs, and low blood glucose). denise :+1::+1::+1:

#7

It sort of is, they make you more insulin sensitive, so you’ll release the correct amount of insulin when you’re supposed to, which for an insulin resistant person will be more, and then you return to baseline much quicker.

My wife’s currently trying Retatrutide, which is the 3rd one, that one hits GLP-1, GIP and Glucagon. Weights flying off her crazy and her blood sugar is way better than on Semaglutide. Doesn’t suppress appetite as much as Semaglutide, but better at the sugar control.

(Bob M) #8

I heard they had more drugs coming that were even better, including modifying glucagon. It’s good that this one works as well as it does for your wife.

Edit: I’m not sure why the formatting is weird. I don’t have “I asked Chat CPT about this” as bold, for instance.

I asked Chat GPT about this:

How do glp-1 agonists raise insulin?

GLP-1 agonists (glucagon-like peptide-1 receptor agonists) raise insulin levels through a glucose-dependent mechanism , meaning they increase insulin secretion only when blood glucose levels are elevated . Here’s how it works:

1. Mimic Natural GLP-1 Hormone

GLP-1 is a hormone secreted by the L-cells of the intestine after eating. It’s part of the incretin effect , which enhances insulin secretion from the pancreas in response to food intake. GLP-1 agonists (like semaglutide, liraglutide, etc.) mimic this hormone.

2. Stimulate Insulin Release

GLP-1 binds to GLP-1 receptors on pancreatic β-cells , which:

  • Increases intracellular cyclic AMP (cAMP) levels.
  • Activates protein kinase A (PKA) and Epac2 signaling.
  • Enhances glucose-stimulated insulin secretion .

Importantly, this effect is glucose-dependent — insulin is only released if blood glucose is elevated. So:

  • High blood sugar → GLP-1 agonist boosts insulin.
  • Normal or low blood sugar → minimal or no insulin stimulation, reducing hypoglycemia risk.

3. Additional Effects Supporting Insulin Action

  • Suppresses glucagon from α-cells, lowering hepatic glucose output.
  • Slows gastric emptying , reducing post-meal glucose spikes.
  • Reduces appetite and food intake , which can improve insulin sensitivity over time.

Summary:

GLP-1 agonists raise insulin by enhancing the normal post-meal incretin effect , activating GLP-1 receptors on β-cells, but only in the presence of high glucose levels , making them safer than some older drugs like sulfonylureas that stimulate insulin regardless of glucose level.

Using the incretin effect is helpful, because then insulin is only raised in response to eating, unlike how we think of insulin, as being higher when it shouldn’t.

#9

Sounds right! Forget about the Incretin, remember hearing that one a couple years ago when I started here and there with Semaglutide before the boom happened. Just looked it up and Retatrutide is already in phase 3 trials and expected to be out next year…LOL! I feel bad for whatever the hell that’s gonna cost when it’s in the wild. It’s kinda pricey now at around $60 for 10mg of it. Although Semaglutide averages $800-$1000 for 5mg, and it’s been out for a few years now. I like my $60 price myself.:rofl::rofl::rofl: