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A large new study just published in JAMA is making headlines, and for good reason. It found that some commonly prescribed type 2 diabetes medications, specifically sulfonylureas, may be linked to a significantly increased risk of cardiovascular events, including heart attacks, strokes, and death.
If you’re currently taking a sulfonylurea or considering medication options, this is essential information you need to know.
What Are Sulfonylureas?
Sulfonylureas are one of the oldest classes of diabetes medications. Drugs like glipizide, glyburide, and glimepiride help lower blood sugar by stimulating your pancreas to produce more insulin.
They’re often used as a second-line medication after metformin or as a cheaper alternative when cost is a concern. But they’ve long had a reputation for causing low blood sugar (hypoglycemia) and weight gain, and now, cardiovascular concerns are back in the spotlight.
What This Study Found
Researchers from Harvard and the Brigham and Women’s Hospital reviewed data from over 1.2 million people with type 2 diabetes across two large U.S. databases. They looked at people who were taking either a sulfonylurea, a DPP-4 inhibitor (like sitagliptin), or an SGLT-2 inhibitor (like empagliflozin).
The study results:
- People on sulfonylureas had a 34 percent higher risk of heart attack, stroke, or death compared to those on SGLT-2 inhibitors
- Compared to DPP-4 inhibitors, the risk was still higher, about 16 percent increased risk
- These risks appeared early in treatment and continued over time, not just in older adults or those with existing heart disease
- The study found Glipizide had the highest risk and suggested caution in prescribing this to any person with moderate cardiovascular risk or established cardiovascular disease.
Why Is This Concerning?
The study adds to a growing body of evidence suggesting that not all diabetes medications are created equal when it comes to heart health. While sulfonylureas are effective at lowering blood sugar, that benefit may come with trade-offs, especially for your heart.
And considering that people with type 2 diabetes already have a higher risk of cardiovascular disease, this could be a double hit.
What Should You Do?
If you’re currently taking a sulfonylurea, don’t panic, but don’t ignore this either.
- Talk to your doctor or pharmacist. Ask if your current medication is a sulfonylurea and whether it’s still the right option for you
- Ask about newer alternatives, especially if you have other cardiovascular risk factors
Expert Opinion
From a scientific perspective, this study supports what prior trials have hinted at: sulfonylureas may carry cardiovascular risks that other newer medications do not.
Earlier studies like the ADVANCE trial and UKPDS showed mixed cardiovascular results for sulfonylureas, but more recent observational data, including this new analysis, suggest the risks may be more pronounced than previously thought.
The American Diabetes Association has already emphasized that treatment should be individualized based on cardiovascular risk, and this study reinforces that recommendation.
Sulfonylurea drugs have minimal A1c-lowering effect of just 0.7%. They force your pancreas to push out more insulin, which worsens insulin resistance. Nutrition can produce way better results, so overall, sulfonylureas are not the best choice of medication.
Key Takeaways
If you have type 2 diabetes, your medication shouldn’t just lower your blood sugar. It should support your overall long-term health, including your heart.
With their minimal effect on lowering A1c, their effect on worsening insulin resistance (a central cause of diabetes), and their effect on heart health – it is certainly time to reassess their role in diabetes care.
At the end of the day, if you can try to minimize the amount of medication you take, the better your health will be.
The fact is, nutrition and lifestyle have better outcomes than medications, so focus your attention there and try to reduce medication use.
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Sulfonylurea FAQs
What is the sulfonylurea mechanism of action?
Sulfonylurea drugs help lower blood sugar by stimulating your pancreas to produce more insulin.
Is glipizide a sulfonylurea?
Yes, glipizide is a sulfonylurea. According to the study glipizide has the highest risk for heart disease and should be prescribed with caution.
Is metformin a sulfonylurea?
No, metformin is not a sulfonylurea medication, it is a biguanide, and is considered one of the safest diabetes medications.
Is glyburide a sulfonylurea?
Yes, glyburide, glipizide, and glimepiride are all sulfonylurea drugs.
Which sulfonylurea causes the most hypoglycemia?
Glyburide (glibenclamide) is the sulfonylurea most associated with hypoglycemia, especially in older adults or those with kidney impairment. However, all sulfonylurea drugs increase risk of hypoglycemia, because their mechanism of action is to produce more insulin.
How does sulfonylureas cause hypoglycemia?
Sulfonylureas cause hypoglycemia by stimulating the pancreas to release insulin, regardless of current blood glucose levels. They bind to receptors on pancreatic beta cells, triggering insulin secretion even when blood sugar is normal or low. This unregulated insulin release can lead to low blood glucose (hypoglycemia), especially if meals are skipped, delayed, or if dosing isn’t adjusted for activity or renal function.
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