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The Unauthorized Biography

by Wil Dubois, BS, AAS, CPT, TPT

So how did metformin achieve this career transformation? It wasn’t until the UK Prospective Diabetes Study (UKPDS) was released in 1998 that the floodgates of acceptance opened. The UKPDS gave American doctors solid clinical evidence of metformin’s effectiveness at both lowering blood glucose and improving cardiovascular outcomes, just at the time when medicine in the United States was moving to a more evidence-based framework. Metformin began to pick up speed, and it hasn’t really hit any stumbling blocks since then.

According to the IMS Health National Prescription Audit, more than 59.1 million prescriptions for metformin were dispensed in the United States alone in 2011. If you’re wondering how 18.8 million people with diagnosed diabetes can use three times as many prescriptions, it’s because each time someone refills a 30- or 90-day supply of metformin, it counts as one prescription. Still, that’s a lot of metformin. Even at a measly four bucks a pop, the drug grosses nearly a quarter of a billion dollars per year in the United States alone. And globally, metformin is the most widely prescribed diabetes drug. Its father, Dr. Sterne, would be proud.

Metformin gets married
Metformin works well with other medicines, giving rise to precious few drug interactions. More than that, combinations of metformin and other glucose-lowering drugs have been shown to be significantly more potent than either medicine alone — and sometimes even more potent than the sum of each drug’s individual effect. Since getting people to take multiple prescription drugs can be a challenge, metformin has been married to a number of other diabetes medicines to create “polypills,” capsules or tablets with more than one drug in them.

Metformin has been combined in diabetes polypills with sulfonylureas (in Metaglip, Glucovance, Amaryl M), thiazolidinediones (ACTOplus met), and DPP-4 inhibitors (Janumet, Galvumet, Kombiglyze XR). Globally, there are now more than 20 polypills containing metformin, and the list is likely to continue to grow as new diabetes drugs are developed.

Metformin’s descendents
Although garden-variety metformin hasn’t really changed in 50 years, several new formulations have been introduced since that time. For people who have a hard time swallowing pills, metformin comes in a liquid formulation called Riomet. The most popular variant, however, is an extended-release version of the drug. Metformin is only absorbed within the body at the very upper part of the gastrointestinal tract, and any portion of the drug that passes further “downstream” is simply excreted. The trick to extending the action of the drug, then, is to keep the pill in the stomach longer while releasing the medicine slowly.

The most commonly prescribed extended-release version of metformin is Glucophage XR. This pill accomplishes its mission with a polymer that turns into a gel in the stomach, which blocks quick absorption of the medicine. This XR formulation has been shown to prolong the absorption of the drug to a peak of around seven hours, compared with traditional metformin’s three-hour peak in working action.

Indian researchers are currently experimenting with a floating pill that would stay in the stomach for even longer, slowly releasing metformin the entire time. For as long as metformin remains a popular diabetes drug, it is a safe bet that researchers will be trying to create new and innovative ways to deliver it to the body.

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