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ForumsMetabolic Health & DiabetesGLP-1 and gluconeogenesis — May 2025

GLP-1 and gluconeogenesis — May 2025

sarah_nash92 Wed, Mar 26, 2025 at 6:16 PM 9 replies 1,616 viewsPage 1 of 2
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sarah_nash92
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Mar 26, 2025 at 6:16 PM#1

A1C went from 7.4 to 5.6 over nine months and my prescriber was more interested in the fasting insulin, which I did not expect.

What I actually want to know is why A1C lags the way it does, and what to look at in the meantime if you want to know sooner.

Numbers rather than impressions, if you have them.

16 11NauseaFreeNow, SteveThurs, B12Beth and 13 others
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pete_manc_UK
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Mar 26, 2025 at 8:02 PM#2
sarah_nash92 said:
A1C went from 7.4 to 5.6 over nine months and my prescriber was more interested in the fasting insulin, which I did not expect.

PCOS success story with glycaemic control: as someone with polycystic ovary syndrome, this medication has been transformative beyond weight loss.

After 12 months: periods became regular for the first time in ever, testosterone levels normalized, acne cleared significantly, and — unexpectedly — my hormonal symptoms have almost completely resolved.

GLP-1 agonists address the insulin resistance at the root of PCOS. For PCOS patients, this isn't "just" a weight loss drug — it's treating our underlying metabolic dysfunction.

Last edited: Mar 27, 2025 at 2:02 AM
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tommy_boulder
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Mar 26, 2025 at 9:48 PM#3
pete_manc_UK said:
PCOS success story with glycaemic control: as someone with polycystic ovary syndrome, this medication has been transformative beyond weight loss.

Patient selection optimization for glycaemic control: emerging predictive biomarkers for GLP-1 agonist response include:

BiomarkerAssociationEvidence Level
Baseline BMIHigher BMI → greater absolute weight lossStrong
Fasting insulinHigher insulin → better responseModerate
GLP1R gene variantsrs6923761 → variable responsePreliminary
Baseline hsCRPHigher CRP → greater CV benefitModerate
Early weight loss (4 wk)≥3% at 4 wks → strong predictor of ≥10% at 68 wksStrong

The 4-week early responder criterion is the most clinically actionable: if you haven't lost ≥3% by week 4 at a therapeutic dose, discuss optimization strategies with your provider.

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SleepFixSam
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Mar 26, 2025 at 11:34 PM#4
sarah_nash92 said:
A1C went from 7.4 to 5.6 over nine months and my prescriber was more interested in the fasting insulin, which I did not expect.

This is my experience too, for whatever a second data point is worth. The detail I would add is minor and it is already implied above.

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ingrid_STO
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Mar 27, 2025 at 9:59 AM#5

From the other side of the consultation, briefly.

Glycemic variability as the key metric for glycaemic control success: my coefficient of variation (CV) on CGM dropped from 42% to 21%. Target is <36%, with <30% being ideal.

Why this matters more than average glucose: large glucose swings cause oxidative stress, endothelial damage, and promote advanced glycation end-products (AGEs). A flat glucose line at 95 mg/dL is metabolically healthier than oscillating between 60 and 160, even if the average is the same.

Last edited: Mar 27, 2025 at 12:59 PM
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