Thread by @sanilrege

🧵It’s Not All GLP-1: Why Psychiatrists Shouldn’t Forget Metformin 🚨1/7

GLP-1 agonists are getting all the hype in psychiatry.

But we shouldn’t forget metformin -less dramatic upfront, but still effective long-term in many patients.

Here’s why psychiatrists should look closer 👇

1/ Metformin’s relevance in psychiatry goes beyond glucose control.

It acts on:

1. Peripheral insulin sensitivity → improves glycaemia

2. AMPK activation → ↓ systemic inflammation & oxidative stress

3. Brain insulin resistance (BIR) → a mechanism now linked to psychosis, mood disorders & treatment resistance

2/ Inside the brain:

- AMPK activation in periphery ↑ glucose uptake

- But in the hypothalamus, AMPK inhibition ↓ NPY signalling & leptin resistance → better appetite regulation

-Enhances secretion of satiety hormones (GLP-1, PYY)

Net effect: appetite regulation, weight stability, metabolic balance

3/ Metformin also shows neuroprotective effects:

- Stabilises the blood-brain barrier (BBB)

-Modulates the gut–brain axis

-Suppresses MMP-9 → ↓ BBB breakdown & neuroinflammation

-Engages PPAR & IGF pathways → neuronal repair & resilience

4/ Clinical evidence:

👉TRIO-BD trial → reversing insulin resistance improved depression, anxiety & functioning in treatment-resistant bipolar disorder

👉Imaging studies → BD + insulin resistance = BBB leakage, worse mood & poorer treatment response

👉Metformin may be disease-modifying, not just symptom-managing.

5/ Practical aspects

For psychiatrists prescribing:

1. XR formulations → better GI tolerability

2. Start early → ideally at AP initiation, not years later

3. Monitor U&E + eGFR regularly

4. Look out for PCOS, prediabetes, or obesity → strong indications

6/ GLP-1s are exciting, but metformin deserves equal attention.

It’s slower, steadier, but potentially reshapes illness course via metabolic + neurobiological mechanisms.

7/ Learn more👉 academy.psychscene.com/courses/antips…