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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 narrow version of the question is why A1C lags the way it does, and what to look at in the meantime if you want to know sooner. If the honest answer is that nobody knows, that is a useful answer and I would rather have it.

— 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…

Fasting insulin is the lab my functional medicine doctor cares about most for glycaemic control: it's a much earlier marker of metabolic dysfunction than glucose or A1C.

My fasting insulin: 28 → 12 → 7 uIU/mL over 9 months. Target is <7. By the time your fasting glucose is elevated, your insulin has been elevated for YEARS trying to compensate.

Ask your doctor to include fasting insulin in your bloodwork panel. It's cheap (~$20) and incredibly informative.

25 20PharmHunterJen, TomTeleRx, DoseLogDan and 22 others
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SarahChen_PharmD
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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 42% to 22%. 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: Jun 26, 2024 at 9:31 AM
24 19paul_denver, TinaHashiRN, robert_kc and 21 others
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Dr.AddMedPHL
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Jun 26, 2024 at 6:38 AM#4
SarahChen_PharmD said:
Glycemic variability as the key metric for glycaemic control success: my coefficient of variation (CV) on CGM dropped from 42% to 22%.

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 = 4.4 (insulin resistant) → Current = 1.2 (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.

23 18TomFromTexas, mike.trainer_LA, sarah_nash92 and 20 others
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wei_SG
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Jun 26, 2024 at 7:14 AM#5
TrialNerd_Beth said:
Fasting insulin is the lab my functional medicine doctor cares about most for glycaemic control: it's a much earlier marker of metabolic dysfunction…

This matches mine closely enough to be worth saying so out loud. Nothing to add that would improve it.

22 17JenPlateau, SallyK_inj, CryptoCarl and 19 others
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