Heart disease is the number-one killer of people with type 2 diabetes, so you would think drugs that help control diabetes would be good for the heart.

But the opposite is sometimes true—some commonly prescribed diabetes drugs actually increase your risk for heart disease.

There are many ways this can happen, explains Debabrata Mukherjee, MD, chief of cardiovascular medicine at Texas Tech University Health Sciences Center El Paso. “Sometimes they can cause hypoglycemia—low blood sugar—which can reduce the amount of nutrients going to the heart. Sometimes they raise bad lipids and lower good cholesterol, or increase water retention [which raises blood pressure] or reduce the ability of the coronary arteries to dilate properly. And some, we don’t understand why they raise the risk for heart disease.”

How could these drugs be developed by the pharmaceutical industry and be approved by the Food and Drug Administration (FDA) yet make people with diabetes more likely to develop heart disease? Read on to find out how we got into this mess—and learn which diabetes drugs actually protect your heart.


Until 2008, clinical studies needed to get diabetes drugs approved by the FDA didn’t have to even look at cardiovascular effects. They just had to show that the drugs lowered blood sugar (glucose). That’s a crucial omission, since the risk for stroke, heart disease and death from heart disease in patients with diabetes is at least twice that of patients without diabetes. So that year, the FDA made it clear to drug manufacturers that it wanted to see new drugs for type 2 diabetes undergo clinical trials to demonstrate cardiovascular safety—in addition to blood glucose effects.

Now we’re seeing the results of these studies. One recent review found that out of the 11 classes of diabetes drugs, drugs in four of them are associated with increased risk.


The following drugs, or drug classes, increase heart disease risk. What to do? That’s simple—avoid them as frontline drugs, says Dr. Mukherjee. The drugs…

• Sulfonylureas (Glucotrol, Micronase). This class of drugs stimulates the pancreas to make more insulin, but it also causes weight gain and increases the risk for heart attacks. And it makes it harder for the body to recover after a heart attack.

• Meglitinides (Starlix, Prandin). This class works similarly to sulfonylureas, also causes weight gain and is associated with negative cardiovascular effects, although less severe.

• Rosiglitazone (Avandia). Approved in 1999, Avandia was severely restricted by the FDA in 2010 when it was shown to greatly increase the risk for strokes, heart attacks and heart failure.

• Saxagliptin (Onglyz). This drug has been linked with an increase in hospitalization for heart failure.


One of the oldest, safest and as it turns out, least expensive drugs is metformin. This should be the initial diabetes drug of choice for most people. “It lowers glucose, provides a little weight loss, and there’s some evidence it can reduce cardiovascular events,” says Dr. Mukherjee. For example, one study found that metformin, when initiated early in the disease, reduces many complications of diabetes—including heart attacks, heart failure and stroke—by 12% overall.

Metformin isn’t right for everyone, however. Some patients have trouble tolerating its side effects, which include GI distress, and caution is recommended for elderly patients and for those with liver or kidney disease.

Others may do fine with metformin but need a second drug to bring blood sugar even lower. However, Dr. Mukherjee recommends caution in trying to get your blood sugar down too low. “We used to think that lower glucose was better,” he says. “We’re beginning to understand there’s a balance, and too low can lead to problems.” (To learn more about this issue, see Bottom Line’s Are Doctors Trying Too Hard to Control Diabetes?)


If you do need another drug besides metformin, these are either neutral or positive for heart health:

• Many DPP-4 inhibitors, which increase insulin release after meals, are neutral and possibly positive for heart health. Examples include Alogliptin (Nesina), Sitagliptin (Januvia), Linagliptin (Tradjenta) and Vildagliptin (Galvus)—and there are combination drugs that pair a DPP-4 inhibitor with metformin.

• GLP-1 agonists (Byetta, Bydureon). These medications, which increase insulin release after a meal, lead to modest weight loss and a moderate decrease in the risk for cardiovascular disease.

• Alpha-glucosidase inhibitors (Glyset, Precose) slow the digestion of carbohydrates, moderating blood sugar rise after meals. They don’t lead to weight gain and may lower blood pressure as well as cardiovascular “events,” such as heart attacks.

• Empagliflozin (Jardiance). This new drug, an SGLT2 inhibitor, slows the rate at which glucose is reabsorbed by the kidneys, thus lowering blood sugar levels. In a recent study, it was found to reduce risk for cardiovascular disease among patients being treated for diabetes who had a high risk for heart disease. The study found a 38% reduced risk in cardiovascular mortality in those who took Jardiance compared with a placebo. In absolute figures, rates of death from cardiovascular causes were 3.7% with empagliflozin versus 5.9% with a placebo. Because of this study, almost two-thirds of physicians said they were prescribing empagliflozin for more patients with diabetes, according to an online poll conducted by Medscape Medical News. The drug is promising, but it is expensive and comes with other risks such as an increased risk for urinary infections. The FDA is also monitoring reports of ketoacidosis, a potentially dangerous condition that requires hospitalization.


“I advocate a balanced approach and looking at the big picture,” says Dr. Mukherjee. That means starting with diet and losing weight if you are overweight, which can make metformin more effective, so that you may not need to consider other options. “There’s so much we can do as individuals with lifestyle changes to avoid drug therapy,” he says.

The good news is that the era in which drug manufacturers could just ignore heart health for diabetes has ended. But you still need to be vigilant. Talk to your doctor about the benefits and risks of any medication you are prescribed, including how it affects your weight and your cardiovascular health. After all, the goal of treating diabetes isn’t to lower your blood sugar numbers but to help you live a long and healthy life—with a healthy heart.