Pharmacotherapy Newsletter

Volume 1, Issue 36, 09/21/2009

Question

What is the mechanism by which metformin (Glucophage®) can improve the lipid profile beyond its glucose lowering properties in type 2 diabetes mellitus (T2DM)?

Answer

It is well known that patients with type 2 diabetes mellitus (T2DM) are characterized as having central obesity (or increased abdominal visceral fat), hepatic insulin resistance, decreased peripheral insulin mediated glucose uptake (despite elevated insulin levels), excessive or accelerated "basal rates" of hepatic glucose production (or hepatic gluconeogenesis), and abnormal lipid profiles that are considered to be more "atherogenic".(1-3)

Unfortunately, several glucose lowering agents (sulfonylureas, thiazolidinediones, and insulin in particular) are also associated with an increase in weight - a problem already implicated in T2DM.  As it relates to cholesterol, many cases show that an improvement in the glucose levels will improve the lipid profile (generally through a reduction in very low density lipoprotein (VLDL) output from the liver since it is directly tied to blood glucose levels).(2-4)  However, not all glucose lowering medications have a beneficial and direct effect on the lipid profile beyond their glucose lowering properties.(2,4)  Given the characterization of most type 2 diabetics, any intervention that could not only significantly improve glucose control, but that would also cause weight loss or at least not weight gain, have a good history of safety, and improve the lipid profile beyond the glucose lowering properties would be ideal.  Fortunately, metformin...

The complete answer to this question comes with a diagram that explains the mechanism for this improvement on the lipid profile.

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