That old standby, metformin, is still your best bet. In fact, there is no benefit in taking the newer oral medications unless you can't tolerate the older ones.

That was the conclusion of researchers from Johns Hopkins University who examined 216 controlled studies and two systematic reviews in order to compare older oral medicines (second-generation sulfonylureas and metformin) and newer medications (thiazolidinediones, meglitinides, and alpha-glucosidase inhibitors) with regard to medium-term effects on A1c levels, lipid levels, body weight, and adverse outcomes.

Overall, the researchers found metformin to have the best benefit to risk ratio. Metformin was similar to or even better than the other oral medicines with regard to blood sugar control and lipid levels, though it was associated with greater risk of gastrointestinal problems.

In addition, it did not cause the 2.2 to eleven pound weight gain associated with almost all the other medicines. Second-generation sulfonylureas did pretty well too, apart from a greater risk of hypoglycemia.

Compared with newer agents, both metformin and sulfonylureas had three distinct advantages: longer use in practice, more information about longer-term effects, and lower cost. Metformin is available generically for about $40 monthly, for example, while Avandia can cost over $250 monthly.

Thiazolidinediones (like Actos and Avandia) were found to have a lower risk for hypoglycemia and a small beneficial effect on healthy cholesterol (HDL) levels, but were no better at lowering blood glucose and were also associated with adverse effects on bad cholesterol (LDL), weight, and risk of congestive heart failure.

(The researchers noted that large, longer-term comparative studies are still needed on outcomes such as myocardial infarction, chronic kidney disease, and cardiovascular mortality, as this review focused only on medium-term effects.)

The study review, which was commissioned in May 2005 by the federal Agency for Healthcare Research and Quality, has been used by Consumer Reports as the basis for its "best buy" evaluations of oral diabetes medications. In sum, Consumer Reports concluded that newer drugs are no better, no safer, and certainly more expensive.

Sources: Annals of Internal Medicine, September 2007
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