Study Compares 'Add-On' Drugs for Diabetes

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Study Compares 'Add-On' Drugs for Diabetes

News Review from Harvard Medical School

June 11, 2014

News Review From Harvard Medical School -- Study Compares 'Add-On' Drugs for Diabetes

A new study suggests that insulin might not be the best drug to add to metformin in the treatment of people with type 2 diabetes. But outside experts questioned the conclusions. The study was based on records from the U.S. Veterans Health Administration, Medicare and the National Health Index. People in the study had been taking metformin. Doctors added a second drug to better control their blood sugar. For about 2,400 people, that drug was insulin. Another 12,000 people added a type of drug called a sulfonylurea. In the next 14 months, both groups had similar rates of heart attack and stroke. But people who took insulin had a 44% higher death rate. Outside experts told HealthDay News that other factors may have caused the difference. People who got insulin were sicker, an American Diabetes Association official noted. Their blood sugar rates were higher than those who got the other drug. It's not surprising that they would have higher death rates, he said. Another recent study also reached opposite conclusions. It found no difference in heart attacks, strokes or death between groups taking one of these add-on drugs. The Journal of the American Medical Association published the study June 11.



By Howard LeWine, M.D.
Harvard Medical School


What Is the Doctor's Reaction?

The best treatment for type 2 diabetes is diet and exercise. For some people, losing as few as 10 pounds, combined with 30 minutes of exercise daily, can bring blood sugar levels back into the normal, healthy range. But most people need drug treatment.

The widely accepted first drug to use is metformin. Metformin works on the main cause of type 2 diabetes, insulin resistance. Cells in the body need insulin to move sugar out of the bloodstream and into cells. Insulin resistance is what happens when this process doesn't work well.

Type 2 diabetes increases your risk of heart attack, stroke and early death. Metformin can lower your risk of these complications and death. But what if metformin is not keeping blood sugar in control? What is the best drug to add on to metformin?

This study compared two of the commonly prescribed add-on drugs for type 2 diabetes, a type of pill known as a sulfonylurea or insulin injections. Examples of sulfonylurea drugs include:

  • Glipizide (Glucotrol)
  • Glyburide (DiaBeta, Micronase)
  • Glimepiride (Amaryl)

These medicines encourage your pancreas to make and release more insulin.

The study was designed to look at which of these add-on drugs was linked with a higher rate of heart attack, stroke and death. The researchers expected the metformin-insulin combination to fare better, for three reasons:

  • In general, insulin is more effective at lowering blood sugar.
  • If you take insulin, the pancreas doesn't need to work as hard to make more insulin to overcome insulin resistance. So the pancreas is less likely to burn out.
  • Some studies of sulfonylureas for type 2 diabetes have linked their use with a higher risk of heart attack and stroke.

But the study results showed the opposite. Adding insulin to metformin was linked with a significantly higher death rate than adding a sulfonylurea. Heart attack and stroke risk were about the same for both combinations.


What Changes Can I Make Now?

Diabetes experts not involved in the study advise caution in interpreting these results. It's very possible that the people given insulin as add-on treatment had more advanced diabetes or other medical conditions that increased their risk of death.

The results do send a message. Any diabetes drug added on to metformin can lower blood sugar. But that does not mean that it improves quality of life or prolongs life.

If you have type 2 diabetes, the best ways to lower your blood sugar  -- whether or not you take metformin -- is diet and exercise.

Diet -- Maintain a healthy weight and lose weight if necessary. Avoid simple sugars. A Mediterranean-style diet loaded with vegetables and some fruits is an excellent choice. But you still need to watch total calories.

Exercise -- Try to carve out 60 minutes most days of the week for dedicated exercise. But get at least 30 minutes per day. Also, do everything you can to add physical activity throughout your day. Even standing up more of the time may help.


What Can I Expect Looking to the Future?

The results of this study may give doctors some pause before quickly prescribing insulin for people with type 2 diabetes. And perhaps more patients will realize that diet and exercise may prevent them from ever needing insulin or other add-on drug treatment.

Last updated June 11, 2014

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