Should You Use Metformin If You’re On a GLP-1?

One of the most common questions I get is about the interaction between HGH, GLP-1 drugs, and metformin—especially when it comes to blood sugar.

Here’s a perfect example from a recent reader-submitted question:

This is an important question for anyone using peptides, GH, and metabolic optimization tools—so let’s break it down.

Does HGH Really Raise Blood Sugar? The Truth

A lot of people panic when they see their fasting glucose go up after adding HGH—but here’s what you need to know:

✔️ HGH is anti-insulinogenic, meaning it can increase blood sugar by:

• Stimulating gluconeogenesis (your liver produces more glucose)

• Increasing lipolysis, which can lead to a temporary decrease in insulin sensitivity

But…

HGH Raising Blood Sugar Is Not Necessarily a Bad Thing!

This effect is context-dependent and doesn’t always happen.

If you are living insulin-controlled—meaning you’re metabolically healthy, active, and eating well—your body adapts to GH, and your glucose levels may remain stable.

In fact, some studies suggest that HGH-induced increases in fasting glucose are transient and don’t necessarily indicate long-term insulin resistance.

So while yes, HGH can raise glucose, it’s not automatically a problem—especially if you’re controlling for other variables like diet, fasting, and exercise.

How GLP-1 Drugs Affect Blood Sugar

The reader is microdosing Retatrutide three times per week, which means he’s benefiting from:

✔️ Increased insulin sensitivity

✔️ Lower glucose output from the liver

✔️ Slower gastric emptying, reducing post-meal spikes

So naturally, you might be wondering: Do I still need metformin if GLP-1s are already lowering blood sugar?

Metformin vs. GLP-1: Do You Need Both?

Even though GLP-1 drugs and metformin both reduce blood sugar, they work through different mechanisms:

✅ Metformin reduces hepatic glucose production and activates AMPK

✅ GLP-1s increase insulin sensitivity and slow digestion

So, while some people might argue that GLP-1s make metformin unnecessary, I don’t entirely agree.

Here’s why:

My Verdict: Yes, Keep Taking Metformin (For Longevity)

Even if your blood sugar is already under control, I still believe metformin has a place in your stack because of its longevity benefits.

• Key longevity benefits of metformin (even in non-diabetics):

• Activates AMPK, mimicking some of the benefits of fasting

• Reduces inflammation and oxidative stress

• Supports mitochondrial function and autophagy

• May protect against cancer and neurodegeneration

Metformin has strong research supporting its anti-aging effects, even in people with normal glucose levels.

So even though GLP-1 drugs improve glucose control, metformin offers unique longevity advantages you don’t want to miss out on.

When You Might Reduce Metformin

There are a few cases where it might make sense to lower or remove metformin when on a GLP-1:

❌ Your fasting glucose is already low (under 85 mg/dL)

❌ You’re experiencing severe GI issues from metformin that don’t subside (which is usually because you are not cleaning up your diet and lifestyle)

❌ You’re microdosing Retatrutide and your glucose is already well-controlled

In this case, you could experiment with:

• Dropping from 1,000 mg to 500 mg per day

• Cycling metformin (taking it on certain days or after high-carb meals)

But for most people, I’d keep it in your stack—not necessarily for glucose control, but for the longevity benefits.

Final Thoughts: Metformin Is Still Worth It?

Short Answer: Yes, keep taking metformin—not just for blood sugar, but because it’s one of the most powerful anti-aging molecules we have.

Best approach? 

Track your fasting glucose, post-meal glucose, and A1C → If they’re in a good range, you can experiment with metformin dosing, but I wouldn’t remove it entirely.

Want More Deep Dives Like This?

Remeber to submit your questions to my question box.

Best,

Hunter Williams