What Comes After Metformin?

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Comparison of different drugs as add-on treatments to metformin in type 2 diabetes: a meta-analysis, by Matteo Monami and colleagues. Diabetes Research and Clinical Practice 79:196--203, 2008

What is the problem and what is known about it so far

Metformin is recommended as the drug of first choice for type 2 diabetic patients. Many physicians recommend metformin, along with lifestyle changes, at the time of diagnosis. But in most patients, metformin and lifestyle therapy can control blood glucose for only a limited time; most patients need a combination of drugs within a few years. Several types of diabetes drugs can be added when metformin alone is not enough. Most previous studies have looked at how these drugs work either alone or in combination with drugs other than metformin.

Why did researchers do this particular study?

The researchers wanted to learn which drugs work best with metformin for patients whose diabetes remains uncontrolled with a single diabetes drug.

How was the study done?

The researchers looked at data from 27 studies comparing how well various drugs worked with metformin to lower A1C levels (a measure of long-term blood glucose control) in patients whose blood glucose remained poorly controlled using only one medicine.

What did the researchers find?

When added to metformin therapy, sulfonylurea drugs lowered A1C levels by 0.85 percent; adding an alpha-glucosidase inhibitor lowered A1C by 0.61 percent; and adding a thiazolidinedine drug lowered A1C by 0.42 percent compared to adding a placebo (a pill that has no effect) to metformin. When compared directly, sulfonylureas were better than thiazolidinediones in lowering A1C levels and were as effective as adding insulin to metformin. The effects of various diabetes drugs when combined with metformin are usually smaller than the same drugs' effects when used alone.

What were the limitations of the study?

Because this analysis was based on the small number of studies comparing various drugs in combination with metformin, new information from future studies could change the researchers' conclusions. Of the studies examined, factors such as initial A1C levels and subjects' duration of diabetes cold have affected results; because of the small number of available studies, researchers could not take such factors into account.

What are the implications of the study?

Until more studies are conducted, not enough is known to show conclusively that one type of diabetes drug is better than another in combination with metformin, nor that adding insulin is more effective than adding another oral drug. For now, the choice of which drug to add to metformin must be made based on considerations such as patient tolerance, cost, and other medical factors and not on how well the addition will lower A1C levels.

FOR MORE INFORMATION

Medicines for Type 2 Diabetes

Insulin for Type 2 Diabetes

Improving Blood Glucose