Based on NIH | Can metformin cause depression or mood changes, how common is this side effect, and what should I do if I experience it?

Metformin and mood changes: what we know

• Metformin is not widely recognized as a direct cause of depression, but mood changes (including anxiety, irritability, and other behavioral changes) are listed among possible adverse effects for some metformin-containing products, especially combination tablets with sulfonylureas (like glyburide). ^{[1] [2]}
• When mood changes are noted in official labeling for glyburide–metformin combinations, they are often grouped with symptoms of low blood sugar (hypoglycemia), such as shakiness, sweating, confusion, blurred vision, and slurred speech. ^{[1] [2]}
• Hypoglycemia can feel like anxiety, irritability, or rapid mood shifts; this is more likely with sulfonylureas than with metformin alone, but combination products list these neurobehavioral symptoms. ^{[1] [2]}

How common is it?

• Official consumer and professional labels for glyburide–metformin combinations mention “mood changes,” “anxiety,” “irritability,” and “confusion,” but they do not provide a specific frequency estimate for these effects. ^{[1] [3]}
• Because these mood symptoms are often tied to hypoglycemia, their occurrence is expected to be uncommon with metformin monotherapy and more likely when a sulfonylurea is involved or when meals are skipped. ^{[1] [2]}

What the broader research suggests

• Observational data in people with type 2 diabetes suggest that overall use of oral diabetes medicines is associated with a lower risk of developing affective disorders compared with no treatment, with particularly lower risk reported when metformin is combined with a sulfonylurea, though metformin alone did not show a clear protective signal in that analysis. ^[4]
• Small clinical studies have explored whether metformin might improve depressive symptoms in people who have both diabetes and depression, with signals of improved mood and cognition over several months; however, results are preliminary and not definitive. ^[5]
• Reviews have noted mixed findings regarding metformin’s effects on cognition and mood, indicating that evidence isn’t conclusive, and more rigorous trials are needed. ^[6]

Why mood changes can happen

• Hypoglycemia symptoms such as jitteriness, anxiety, irritability, confusion, and mood changes can occur particularly with medications that lower blood sugar beyond the target range; combination products that include a sulfonylurea (like glyburide–metformin) explicitly warn about these symptoms. ^{[1] [2]}
• In many cases, addressing low blood sugar (e.g., eating promptly, adjusting dose with your clinician) can lessen these mood-related symptoms if hypoglycemia is the trigger. ^{[1] [2]}

What to do if you experience depression or mood changes

• Track timing and triggers: Note when symptoms occur and whether they relate to missed meals, heavy exercise without fuel, alcohol intake, or dose changes, because these patterns can suggest hypoglycemia. ^{[1] [2]}
• Check blood sugar during symptoms if you can, since hypoglycemia is commonly associated with anxiety, irritability, and confusion in labeling for glyburide–metformin combinations. ^{[1] [2]}
• Do not stop metformin abruptly on your own, but contact your clinician promptly to review symptoms, blood glucose logs, and all medications, including other diabetes drugs or interacting medicines. ^{[1] [3]}
• Seek urgent care if mood changes come with red-flag signs like severe confusion, slurred speech, or other neurological symptoms, as these may signal significantly low blood sugar or other acute issues called out in official product information. ^{[1] [2]}

When stopping is considered

• While routine mood changes alone are not a standard reason to stop metformin immediately, any severe, unexplained systemic symptoms (like unusual sleepiness, malaise, or breathing changes) warrant urgent evaluation because official guidance instructs immediate discontinuation for suspected lactic acidosis an uncommon but serious condition. ^{[7] [8]}
• If mood symptoms are confirmed to be linked to hypoglycemia from a combination regimen (e.g., glyburide–metformin), your clinician may adjust doses, switch timing, modify diet, or change therapy to reduce lows and associated mood symptoms. ^{[1] [2]}

Practical tips to reduce risk

• Eat regular meals and include a source of complex carbohydrate and protein to stabilize glucose, especially if you’re on combination therapy that can cause hypoglycemia. ^{[1] [2]}
• Limit alcohol and avoid skipping meals, both of which can increase the risk of low blood sugar and related mood symptoms listed in official labeling. ^{[1] [2]}
• Keep rapid glucose sources on hand (glucose tablets, juice) and check your level during symptoms such as shakiness, anxiety, irritability, confusion, or mood swings. ^{[1] [2]}
• Review your full medication list with your clinician to identify combinations that increase hypoglycemia risk and may contribute to mood-related side effects. ^{[1] [2]}

Bottom line

• Metformin by itself is not commonly linked to depression; however, mood changes are mentioned in labeling for glyburide–metformin combinations and are often tied to symptoms of low blood sugar. ^{[1] [2]}
• Research does not show a clear increase in depression due to metformin and, in some contexts, diabetes treatment (including regimens with metformin) has been associated with lower affective disorder risk compared with no treatment, although results vary and are not definitive. ^{[4] [6]}
• If you notice new or worsening depression or mood changes, it’s reasonable to evaluate for hypoglycemia, maintain regular meals, and contact your clinician for personalized adjustments. ^{[1] [2]}