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ForumsPharmacology & MechanismsIncretin effect in healthy vs T2DM — why GLP-1 response is blunted in diabetes Page 2

Incretin effect in healthy vs T2DM — why GLP-1 response is blunted in diabetes

Dr.MetabolicMD Mon, May 25, 2026 at 12:30 AM 13 replies 471 viewsPage 2 of 3
PeptideChemSF
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May 25, 2026 at 3:59 PM#6
Dr.MetabolicMD 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…

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.

Last edited: May 25, 2026 at 7:59 PM
22 17steve_okc, dave_SLC, FDA_TrackerJim and 19 others
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james_edin
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Edinburgh, UK
May 25, 2026 at 10:08 PM#7

A narrower follow-up, since the general answer is now clear:

What did you change at the same time, and can you separate the two now?

21 16Dr.PathRoch, mona_PHX, andrew_nyc and 18 others
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rachel_ABQ
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Albuquerque, NM
May 26, 2026 at 4:17 AM#8
PeptideChemSF said:
Patient selection optimization for glycaemic control: emerging predictive biomarkers for GLP-1 agonist response include: Biomarker Association…

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 → 14 → 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.

20 15AmyNC_wife, SkepticalSean, Dr.CardioMD and 17 others
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Dr.MetabolicMD
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May 26, 2026 at 10:27 AM#9
PeptideChemSF said:
Patient selection optimization for glycaemic control: emerging predictive biomarkers for GLP-1 agonist response include: Biomarker Association…

Glycemic variability as the key metric for glycaemic control success: my coefficient of variation (CV) on CGM dropped from 42% to 19%. 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.

19 14Dr.ObesityMed, HealthEcon_DC, PedsEndoPhilly and 16 others
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greg_boulder
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May 27, 2026 at 3:57 PM#10
rachel_ABQ 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…

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

After 7 months: periods became regular for the first time in years, testosterone levels normalized, acne cleared significantly, and — unexpectedly — I got pregnant naturally after 4 years of trying.

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: May 27, 2026 at 5:57 PM
37 12ben_calgary, patPC_UT, Dr.DermMIA and 34 others
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