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ForumsMetabolic Health & DiabetesGLP-1 and gluconeogenesis — 12 month update

GLP-1 and gluconeogenesis — 12 month update

amsterdam_pete Wed, Jun 26, 2024 at 6:17 AM 9 replies 1,918 viewsPage 1 of 2
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amsterdam_pete
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Jun 26, 2024 at 6:17 AM#1

A reference post rather than a discussion. Corrections are the point; I would rather this be right than mine. It is about glycaemic control, and it is deliberately narrow — everything I am not confident about is marked as such.

What is actually established

HbA1c reflects roughly three months of average glycaemia weighted toward the most recent weeks, which is why repeating it at six weeks tells you very little. The improvement on this class comes from two directions — direct glucose-dependent insulin secretion and glucagon suppression, plus the indirect effect of weight loss on insulin sensitivity — and the second continues after the first has plateaued.

The condition it depends on

The caveat that HbA1c is unreliable in anaemia, haemoglobinopathies and recent blood loss, all of which are commoner than people assume. If it disagrees with fasting glucose or a CGM, that is worth chasing.

The practical version

Because it is glucose-dependent, this class carries a low intrinsic hypoglycaemia risk on its own — the risk arrives when it is combined with insulin or a sulfonylurea, which usually need reducing.

What I am not sure about

The question I want answered is why A1C lags the way it does, and what to look at in the meantime if you want to know sooner. Happy to be told the question itself is wrong.

— amsterdam_pete · corrections welcome and will be edited into this post with credit
26 21JakeSmashed95, NauseaFreeNow, SteveThurs and 23 others
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TrialNerd_Beth
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Jun 26, 2024 at 6:24 AM#2
amsterdam_pete said:
HbA1c reflects roughly three months of average glycaemia weighted toward the most recent weeks, which is why repeating it at six weeks tells you very…

Insulin sensitivity test (HOMA-IR) on glycaemic control — arguably the most important metabolic marker most people aren't tracking:

HOMA-IR = (fasting insulin × fasting glucose) ÷ 405

My numbers: Baseline HOMA-IR = 5.1 (insulin resistant) → Current = 1.3 (insulin sensitive)

Anything above 2.0 indicates insulin resistance. The goal is below 1.5. GLP-1 agonists address the root metabolic dysfunction, not just the symptoms. This is why they work so much better than calorie restriction alone.

25 20PharmHunterJen, TomTeleRx, DoseLogDan and 22 others
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Dr.GastroMayo
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Jun 26, 2024 at 6:31 AM#3
amsterdam_pete said:
HbA1c reflects roughly three months of average glycaemia weighted toward the most recent weeks, which is why repeating it at six weeks tells you very…

Glycemic variability as the key metric for glycaemic control success: my coefficient of variation (CV) on CGM dropped from 36% to 18%. 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.

24 19COA_Karl, MikeFit_NJ, InsuranceTom and 21 others
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VendorMark
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Jun 26, 2024 at 6:38 AM#4
Dr.GastroMayo said:
Glycemic variability as the key metric for glycaemic control success: my coefficient of variation (CV) on CGM dropped from 36% to 18%.

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

After 9 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.

23 18Dr.PeteFamMed, claudia_zurich, nancy_portland and 20 others
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zoe_NC
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Jun 26, 2024 at 7:14 AM#5
TrialNerd_Beth said:
Insulin sensitivity test (HOMA-IR) on glycaemic control — arguably the most important metabolic marker most people aren't tracking: HOMA-IR = (fasting…

This is my experience too, for whatever a second data point is worth. Posting only so the count is not one.

Last edited: Jun 26, 2024 at 8:14 AM
22 17mike_mealprep, NicoleRaleigh, james_edin and 19 others
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