Metformin (metformin)
NOT a GLP-1. First-line diabetes drug with modest weight loss benefit.
Metformin is not a GLP-1 medication. It is the first-line oral medication for type 2 diabetes, used since 1995. Metformin produces modest weight loss (~2-3%) as a side benefit, and is sometimes used off-label for prediabetes, PCOS, and weight maintenance.
Overview
Metformin reduces hepatic glucose production and improves insulin sensitivity. It does not stimulate insulin release directly. It is generic, very inexpensive ($4-15/month), and considered the safest first-line drug for type 2 diabetes.
How Metformin Works
Metformin's primary action is on the liver: it reduces gluconeogenesis (glucose production by the liver) by activating AMPK and inhibiting mitochondrial respiratory chain complex I. Secondary effects include improved insulin sensitivity in muscle and modest reduction in intestinal glucose absorption.
Dosing & Schedule
Standard: 500 mg with meals, titrated to 1000 mg twice daily. Extended-release (XR) is once daily and better tolerated.
Effectiveness — Trial Data
A1c reduction 1.0-1.5%. Weight loss 2-3 kg as side benefit. Significantly weaker than GLP-1s for both diabetes and weight loss.
Side Effects
GI effects (diarrhea 30%, nausea), reduced B12 absorption with long-term use, very rare lactic acidosis (mostly in renal failure). Generally extremely well tolerated.
Cost — How Much Metformin Costs in 2026
$4-15/month generic. Among the cheapest medications in the US pharmacy system.
Who Is Metformin For?
First-line for type 2 diabetes. Off-label for prediabetes, PCOS, weight maintenance after GLP-1 discontinuation.
Metformin Alternatives
For weight loss or diabetes: GLP-1s (semaglutide, tirzepatide), SGLT2 inhibitors, sulfonylureas. Metformin is often used alongside GLP-1s rather than as a replacement.