TZD drug

A group of diabetes drugs called thiazolidinediones (TZDs) have previously left researchers and physicians scratching their heads as to why a set of diabetes drugs that improves insulin sensitivity is frequently linked with weight gain.

This week, researchers, from universities across Georgia, have come up with a convincing answer after finding that TZD drugs affect hunger-stimulating cells within the brain.

The researchers found that, when tested in rodents, the animals were eating more and even waking up in the middle of the night to eat. TZDs work by activating peroxisome proliferator-activated receptor gamma. The researchers from Georgia have now found that in doing so, the drugs also activate agouti-related protein cells (AgRP cells) and when these AgRP cells are activated, they trigger hunger.

So, whilst the drugs have a beneficial effect on increasing sensitivity, the benefit is wiped out, to at least some degree, by the increased stimulus to eat and therefore put on weight.

The checkered history of TZDs

TZD drugs, whilst hailed as a very promising treatment when they were first approved in 1999, have since fallen out of favor with physicians, partly on account of the drugs’ inability to help with weight loss, but also because the drugs have made headlines for having links with serious health risks.

In 2010, TZD drug Avandia (rosiglitazone) was linked with significantly increased rates of heart failure and heart attacks in patients taking the drugs and subsequently the drug was prescribed far less regularly than it had been and was banned in a number of European countries.

Actos (pioglitazone), another TZD drug, has also been linked with a higher risk of health problems. In May 2012, a study linked the drug with a notable increase in risk of bladder cancer. Whilst cases of bladder cancer were still relatively rare, the risk was enough to cause TZDs to be viewed as potentially more of a risk than a benefit when compared to newer classes of drugs.

TZDs are still prescribed in the US, and a number of other countries, but their use has diminished substantially over recent years in light of the risks associated with the drugs.