Can metformin (biguanide) cause hypoglycemia (low blood sugar)?

From the Guidelines

Metformin alone rarely causes hypoglycemia, as it works by decreasing glucose production in the liver and improving insulin sensitivity, rather than directly increasing insulin secretion. This mechanism allows metformin to lower blood glucose levels toward normal without typically dropping them below normal ranges 1. However, hypoglycemia can occur in specific situations: when metformin is combined with other diabetes medications (especially insulin or sulfonylureas), during prolonged fasting, with excessive alcohol consumption, with intense exercise, or in patients with liver or kidney dysfunction. Elderly patients and those with malnutrition may also be at higher risk.

Some key points to consider:

• Metformin is effective and safe, and reduces risks of microvascular complications, cardiovascular events, and death 1.
• The combination of metformin and a DPP-4 inhibitor was associated with a lower risk for severe hypoglycemia than metformin plus a sulfonylurea (high-quality evidence) 1.
• Metformin monotherapy was associated with a lower risk for genital mycotic infections than metformin plus an SGLT-2 inhibitor (moderate-quality evidence) 1.
• Metformin had a greater benefit on weight than all agents except the SGLT-2 inhibitors, and SGLT-2 inhibitors were more effective than metformin in reducing blood pressure 1.

If you're taking metformin, be aware of hypoglycemia symptoms such as shakiness, sweating, confusion, and dizziness. To minimize risk, take metformin with meals, maintain regular eating patterns, monitor blood glucose if prescribed, and inform your healthcare provider about any other medications you're taking. If you experience symptoms of low blood sugar, follow the 15-15 rule: consume 15 grams of fast-acting carbohydrates and recheck your blood sugar after 15 minutes.

From the FDA Drug Label

Metformin hydrochloride tablets rarely cause hypoglycemia (low blood sugar) by themselves. However, hypoglycemia can happen if you do not eat enough, if you drink alcohol, or if you take other medicines to lower blood sugar.

Metformin rarely causes hypoglycemia by itself, but the risk of hypoglycemia may increase when combined with other factors such as:

• Not eating enough
• Drinking alcohol
• Taking other medicines to lower blood sugar It is essential to be aware of these potential risks and take necessary precautions to minimize them 2.

From the Research

Metformin and Hypoglycemia

• Metformin is a biguanide commonly used to treat type 2 diabetes, and it is known for having a low risk of inducing hypoglycemia compared to other oral hypoglycemics or insulin 3.
• However, there have been case reports of patients developing symptomatic hypoglycemia while being treated with metformin, suggesting that there is a risk of hypoglycemia with therapeutic doses of metformin 4.
• One study reported a case of severe hypoglycemia in an elderly patient treated with metformin, which was suspected to be caused by additional blood glucose-lowering effects of other medications and suboptimal nutrition 5.

Factors Contributing to Hypoglycemia

• The risk of hypoglycemia with metformin may be increased when it is combined with other medications that have blood glucose-lowering effects, such as ACE inhibitors and NSAIDs 5.
• Patients should be educated to take metformin with meals to reduce the risk of metformin-associated hypoglycemia 4.
• The risk of hypoglycemia with metformin is generally considered to be low, but it is still important for patients to be aware of the symptoms of hypoglycemia and to monitor their blood glucose levels regularly.

Comparison with Other Medications

• Metformin is often compared to other glucose-lowering medications, such as sulfonylureas, which have a higher risk of hypoglycemia 6, 7.
• Sulfonylureas are potent glucose-lowering drugs, but they can increase the risk of hypoglycemia, especially when used in combination with other medications 7.
• Newer glucose-lowering medications, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, may have a lower risk of hypoglycemia and additional benefits for patients with cardiovascular and renal disease 3.