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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
HPLC_Greg
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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…

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 = 1.1 (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.

Last edited: May 25, 2026 at 9:59 PM
22 17SallyK_inj, CryptoCarl, MariaRD and 19 others
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MounjBrad
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May 25, 2026 at 10:08 PM#7

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

How long did you give it before you decided it was working?

Last edited: May 26, 2026 at 3:08 AM
21 16ben_calgary, patPC_UT, Dr.DermMIA and 18 others
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Dr.EndoIndy
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May 26, 2026 at 4:17 AM#8
HPLC_Greg said:
Insulin sensitivity test (HOMA-IR) on glycaemic control — arguably the most important metabolic marker most people aren't tracking: HOMA-IR = (fasting…

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.

20 15marcus_mpls, DeniseRN_TPA, SandraNC_45 and 17 others
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Dr.MetabolicMD
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May 26, 2026 at 10:27 AM#9
HPLC_Greg said:
Insulin sensitivity test (HOMA-IR) on glycaemic control — arguably the most important metabolic marker most people aren't tracking: HOMA-IR = (fasting…

Glycemic variability as the key metric for glycaemic control success: my coefficient of variation (CV) on CGM dropped from 40% 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.

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

Last edited: May 27, 2026 at 9:57 PM
37 12GenomicsKate, Dr.ObesityMed, HealthEcon_DC and 34 others
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