A1C increased

[wkndworrier]

I've been on Retatrutide for about 2 months at 4mg per week for the last month and am generally pleased with the fat loss and body composition changes (consistently about 1lb per week without much impact to strength).

I had some labs drawn and was surprised to see that my A1C had risen to 5.4 from 5.1 - which was the result of a few months on Tirzepitide, but only taking 1.5mg per week. My baseline has been 5.4 - 5.5 for the last decade, pre any GLP1 drug. My fasting glucose was 87, which is definitely lower than my typical baseline of mid-high 90s. Does the glucagon receptor agonist slightly raise blood sugar?

 

[diogenes]

Relative to tirzepatide, yes. Studies find A1C falls more on tirz than reta.

Glucagon mobilizes glycogen into glucose, so reta can increase blood glucose, hence higher A1C. But for most people on reta, the A1C decrease from reduced food (esp carb) intake means A1C falls overall. That seems not to be the case for you, but that isn't necessarily bad.

A1C 5.5 is normal, not a sign of metabolic problems. And small changes in A1C below 5.7 aren't necessarily instructive. You might ask your doc to measure your insulin sensitivity. That is a more robust measure of metabolic health than 0.3 points of A1C variation within normal range.

Visceral fat is itself harmful to metabolism. If your waist is shrinking to a healthier width, that is a good sign for your metabolism. Trust the process.

 

[BioDad]

I've been on Retatrutide for about 2 months at 4mg per week for the last month and am generally pleased with the fat loss and body composition changes (consistently about 1lb per week without much impact to strength).

I had some labs drawn and was surprised to see that my A1C had risen to 5.4 from 5.1 - which was the result of a few months on Tirzepitide, but only taking 1.5mg per week. My baseline has been 5.4 - 5.5 for the last decade, pre any GLP1 drug. My fasting glucose was 87, which is definitely lower than my typical baseline of mid-high 90s. Does the glucagon receptor agonist slightly raise blood sugar?

I agree with @diogenes that there is a process to it and over time, based on research and anecdotal evidence, you'll likely see those numbers normalize a bit to what they were.

As to your question, theoretically a glucagon receptor agonist would increase glucose levels, by driving glycogen breakdown and gluconeogenesis in the liver. However, also theoretically, with the added GLP-1 and GIP support simultaneously, might mitigate the effects.

I've looked at just about every study I could get my hands on regarding this, and only one study measured glucose-related markers as early as 12 weeks. The rest all waiting until 24 weeks, missing the opportunity to see if glucose initially goes up. All of the papers, however, we're on type 2 diabetics with an A1C in the 8's and fasting glucose in the 100's, so there was also a lot of room for improvement in those folks.

 

[wkndworrier]

Thanks so much, @diogenes and @BioDad - very helpful. My profile is outside of the Retatrutide (or any GLP drug) trial. I'm seeking an optimal state and have been experimenting with various peptides for the last year (under a Dr's supervision - but he is using me as a test case and measureing the impact on an otherwise healthy person). So, I'm doing Retatrutide for two reasons 1) get rid of my flab and 2) longevity and get to a metabolic ideal. I have some sleep/stress issues that I can't fix unless I switch careers - it's caused some mild insulin resistance. However, Retatrutide in only two months has dropped my fasted insulin from 9 to 5. Also a 15 pt drop in LDL (after already being on a statin). So some real wins there outside of weightloss.

I strength train religiously and my starting weight was 207lbs at 19.1% BF - but at 49, and despite being muscular and fit, I have spare tire around lower abs and love handles. I've lost 2" off that area in 2 months and waist is also down 2" - losing about 1lb per week. I'm going to continue with Retatrutide at 4mg per week for the next 3 months and retest. I realize there are a lot of conflicting opinions on A1C within the "normal" range, but I'm hoping to get myself to a consistent 4.8-5.0. I have my diet as optimized as I can. I get a lot of nighttime cortisol spiking my glucose (wore a CGM).

 

[diogenes]

You can probably get rid of that flab, but I question the wisdom of targeting A1C that low. 5.5 is fine. There isn't clear evidence that lowering it to 4.8-5.0 is better.