Metformin + Dihydroberberine

Happy Wednesday!

Today I’m diving deep into a question I get almost every week.

Here’s the most recent one I received:

If you’re on the fence about which route to take, or wondering whether to combine them, this breakdown is for you.

What Are Metformin, Berberine, and Dihydroberberine?

Metformin is the most prescribed diabetes medication worldwide.

It’s an old, trusted pharmaceutical that lowers blood sugar by blocking glucose production in the liver and improving insulin sensitivity.

Its magic comes from activating AMPK (the “metabolic master switch”), which ramps up energy use and makes your body more insulin-sensitive.

Besides blood sugar, metformin has a massive body of research on its anti-aging, fat loss, and even cancer-protective benefits.

Berberine is a natural compound extracted from plants like barberry.

In head-to-head studies, berberine actually rivals metformin for blood sugar control, primarily by activating AMPK.

But traditional berberine has a catch.

It’s notoriously hard to absorb, which is why most people have to take 1,000–1,500mg a day just to get clinical results.

This dosage often leads to gut issues in many people.

Dihydroberberine (DHB) is the next-gen version.

It’s a hydrogenated form of berberine that’s about 5x more bioavailable.

Your body absorbs and uses it much better, with lower doses.

Once inside you, DHB rapidly converts back to active berberine.

That’s why a mere 100–200mg of DHB can outperform a full gram of regular berberine (and with far fewer GI complaints).

For the modern biohacker, DHB is hands-down the better option over standard berberine.

Why Not Both?

I don’t view metformin and dihydroberberine as “either/or” competitors.

Their real power comes when you use them together.

A huge 2024 meta-analysis pooled 50 clinical trials (over 4,000 patients) and found that adding berberine to standard hypoglycemic drugs like metformin lowered fasting blood sugar and HbA1c by an extra 0.7% on average compared to the drug alone.

That’s on top of what metformin already does.

Triglycerides and LDL cholesterol dropped more than 15% further, and insulin sensitivity (measured by HOMA-IR) improved by up to 20% beyond monotherapy.

In cell and animal studies, stacking metformin and berberine (at very low doses) reduced liver fat and blood sugar far more than either one alone, and at about 25–50% of the usual dose.

What to Expect

What does this all mean in real life? Expect improvements across every major marker of metabolic health:

• Blood Sugar: Most people see fasting glucose drop by 10–15 mg/dL after a few weeks, and HbA1c will come down by up to 1.5% over a few months if both are used together.

• Fat Loss: By activating AMPK, you burn more stored fat and reduce liver fat, making it easier to shed weight.

• Lipid Profile: Triglycerides and LDL can drop by 10–20%. HDL may rise slightly.

• Inflammation: Both compounds lower systemic inflammation and oxidative stress.

• Gut Health: Both shift the microbiome toward more beneficial species (like Akkermansia), which translates to better insulin sensitivity and less systemic inflammation.

Because you can use lower doses of each, GI side effects are way less likely than if you crank up a single agent.

Most users report little to no bloating, gas, or cramping with this combo, especially if you use DHB over standard berberine.

Who’s a Good Candidate?

Honestly? Almost anyone who wants to optimize their metabolic health, cut body fat, and protect against chronic disease.

Best candidates include:

• Anyone with insulin resistance, prediabetes, or full-blown type 2 diabetes

• Overweight/obese individuals looking to lean out

• Athletes and high-performers who want to maximize glucose utilization and recovery

• Those with a family history of cardiovascular disease, fatty liver, or metabolic syndrome

• Biohackers focused on longevity and anti-aging (AMPK activation is huge here)

Not for:

If you have chronic kidney disease, a history of lactic acidosis, or are pregnant/nursing, consult your physician before using either agent.

People with super-low fasting blood sugar should be careful, as this combo can make glucose drop further.

My Dosing Protocol

Here’s what I personally recommend and do myself:

Morning:

• 500mg metformin

• 500mg dihydroberberine (DHB)

Evening (before or with dinner):

• 500mg metformin

• 500mg DHB

This gives you robust AMPK activation all day and night, covers both hepatic glucose output and peripheral insulin sensitivity, and leverages the gut/liver synergy both compounds provide.

With DHB, you don’t need to push the dose higher. 500mg is more than enough due to its high bioavailability.

Tip: If you’re new to either compound, start at half-dose for 3–5 days to assess GI tolerance before ramping up.

Final Thoughts

Ready to try this stack and feel the difference for yourself?

Check out BioAbsorb, my go-to dual formula that gives you pharmaceutical-grade metformin plus dihydroberberine in precisely the right clinical doses.

Each serving is formulated for maximum synergy and absorption (no fillers, no garbage).

And don’t forget, you can get 15% off everything at BioLongevity Labs until tomorrow at midnight PST.

And if you use code HUNTERW at checkout, you’ll stack another 15% off.

This is the single best way to upgrade your metabolic health, longevity, and body composition.

Best,

Hunter Williams