Medication·Interactions & depletion·Reviewed June 9, 2026
Metformin interactions.
Metformin has 14 documented interactions in the NutriStack database. Prolonged use is also associated with lower Vitamin B12 and Folate. The full interaction list, depletion table, and replacement suggestions are below. None of this is a substitute for your prescriber's advice.
Metformin at a glance.
A quick, data-grounded summary. The full tables are below.
Metformin has 14 documented interactions in the NutriStack database. Prolonged use is also associated with lower Vitamin B12 and Folate. The full interaction list, depletion table, and replacement suggestions are below. None of this is a substitute for your prescriber's advice.
Substances that interact with metformin.
Every supplement and medication in the NutriStack database with a documented interaction with this drug, highest-severity first. Open any pair for the mechanism and sources.
| Substance | Interaction | What happens |
|---|---|---|
| Alpha-Lipoic Acid | Caution | Alpha-lipoic acid (ALA) has its own blood glucose-lowering effects through improved insulin sensitivity and enhanced glucose uptake. When combined... details → |
| Berberine | Caution | Both metformin and berberine lower blood glucose through overlapping mechanisms including AMPK activation. Combined use creates a significant risk... details → |
| Berberine HCl | Caution | Berberine HCl has independent glucose-lowering effects in type 2 diabetes. When combined with metformin, fasting glucose and A1c may fall more than... details → |
| Chromium | Caution | Chromium supplementation enhances insulin sensitivity and may improve glucose metabolism. When combined with metformin, the additive... details → |
| Fenugreek | Caution | Fenugreek seed extracts (typically standardized to ~50% galactomannan fiber and 4-hydroxyisoleucine) lower fasting glucose and HbA1c in randomized... details → |
| Furosemide | Caution | Furosemide can cause volume depletion and renal impairment, which increases the risk of metformin-associated lactic acidosis. This is particularly... details → |
| Vitamin B12 | Caution | Long-term metformin use (typically >6 months) reduces vitamin B12 absorption by 10-30%, leading to deficiency in up to 30% of chronic users. B12... details → |
| Psyllium Husk | Timing Sensitive | Psyllium forms a viscous gel that slows gastric emptying and can bind oral drugs in the gut, modestly reducing their absorption. Metformin is a... |
| Coenzyme Q10 | Synergy | Metformin inhibits mitochondrial respiratory chain complex I, which is part of how it lowers hepatic glucose output but also contributes to lactate... |
| Inositol | Synergy | Myo-inositol and D-chiro-inositol act as second messengers downstream of the insulin receptor and improve insulin sensitivity, fasting glucose, and... details → |
| Magnesium Glycinate | Synergy | Magnesium is a cofactor for insulin receptor signaling and low intracellular magnesium contributes to insulin resistance, a problem common in type 2... details → |
| Methylcobalamin | Synergy | Metformin reduces serum vitamin B12 by impairing calcium-dependent ileal absorption of B12-intrinsic factor complexes. Meta-analyses report B12... details → |
| Methylfolate | Synergy | Metformin can lower serum folate as well as vitamin B12, with longer treatment duration linked to lower folate levels and higher homocysteine.... details → |
| Vitamin D3 | Synergy | Vitamin D deficiency is common in type 2 diabetes and is associated with insulin resistance. Meta-analyses of vitamin D supplementation in type 2... details → |
What metformin can deplete.
Nutrients this medication is associated with lowering over time, with the mechanism, a suggested replacement where one applies, and the biomarker to monitor. Discuss any replacement with your prescriber first.
| Nutrient | Severity | How it happens | Replace with | Monitor |
|---|---|---|---|---|
| Vitamin B12 | Significant | Metformin impairs calcium-dependent uptake of the intrinsic factor-B12 complex in the terminal ileum, lowering B12 absorption during long-term use. | Methylcobalamin | Serum B12 + methylmalonic acid |
| Folate | Moderate | Long-term metformin use is associated with lower folate status, likely through impaired intestinal absorption and altered enterohepatic handling. | Methylfolate | Serum folate or RBC folate |
The full metformin profile.
Uses, typical dosing, side effects, and the cited evidence for this medication.
Common metformin questions.
Quick answers drawn from the tables above.
What interacts with Metformin?
In the NutriStack database, Metformin has 14 documented interactions. The most notable include Alpha-Lipoic Acid, Berberine, Berberine HCl, Chromium, and Fenugreek. Check any specific combination before taking it and confirm with your prescriber.
Does Metformin deplete any nutrients?
Metformin is associated with lowering Vitamin B12 and Folate with prolonged use. Useful biomarkers to monitor include Serum B12 + methylmalonic acid and Serum folate or RBC folate. Ask your prescriber before adding any replacement supplement.
Is it safe to take Alpha-Lipoic Acid with Metformin?
NutriStack classifies the Alpha-Lipoic Acid and Metformin pairing as caution: Alpha-lipoic acid (ALA) has its own blood glucose-lowering effects through improved insulin sensitivity and enhanced glucose uptake. When combined with metformin, the... Monitor blood glucose more frequently when adding alpha-lipoic acid to metformin therapy. Start with a low ALA dose (300mg/day) and titrate slowly.... Always confirm with your prescriber.
Check your whole stack
See how metformin fits your supplements.
NutriStack screens your full routine for interactions and depletions, and updates the moment you change it.