NutriStack
Glyburide and Milk Thistle, a caution.
A 6-month RCT in 59 patients found that adding silymarin 200 mg three times daily to glyburide improved HbA1c and postprandial glucose more than glyburide alone. Silymarin is a weak CYP2C9 inhibitor in vitro and reduces fasting glucose independently. The combination meaningfully amplifies glyburide's hypoglycemic effect, and glyburide already carries the highest hypoglycemia risk among sulfonylureas, especially in older adults and renal impairment.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- Glyburide and Milk Thistle
- Pair type
- Caution
- Evidence (highest tier)
- Moderate
- Source citations
- 2 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Moderate evidence
Caution
What is happening. A 6-month RCT in 59 patients found that adding silymarin 200 mg three times daily to glyburide improved HbA1c and postprandial glucose more than glyburide alone. Silymarin is a weak CYP2C9 inhibitor in vitro and reduces fasting glucose independently. The combination meaningfully amplifies glyburide's hypoglycemic effect, and glyburide already carries the highest hypoglycemia risk among sulfonylureas, especially in older adults and renal impairment.
Mechanism. Silymarin (the milk thistle flavonolignan complex) modestly inhibits CYP2C9, which metabolizes glyburide, potentially raising its plasma levels. Silymarin also has independent antihyperglycemic actions via improved insulin sensitivity and reduced oxidative stress in pancreatic islets. The combined pharmacokinetic and pharmacodynamic effects amplify hypoglycemia risk.
Recommendation. Tell your prescriber before adding milk thistle on glyburide. Monitor fasting and bedtime glucose for at least 4 weeks and ask whether your glyburide dose should be reduced. Avoid the combination entirely if you have CKD or are over 75.
Sources (2)
- Hussain SA. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J Med Food. 2007;10(3):543-547. PMID 17887949
- Voroneanu L, Nistor I, Dumea R, Apetrii M, Covic A. Silymarin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Diabetes Res. 2016;2016:5147468. PMID 27340676
Stack Score
How this pair moves the number.
Effect on the composite score
If both Glyburide and Milk Thistle are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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