Scientists find type 2 diabetic drugs can have the opposite effect from intended

by Barbara Hewitt on September 25, 2015

A group of drugs often used to treat type 2 diabetes could actually promote the release of sugars into the blood, something they are supposed to prevent, scientists have discovered.

Graham Ladds, a lecturer in pharmacology at the University of Cambridge in the UK points out that there is a continual need to evaluate and study medications and this is the reason why.

diabetesDRUGS‘We discovered previously unidentified effects associated with a commonly prescribed diabetic medication. We found evidence that, in some cases, the treatment could actually promote the release of sugars into the blood the opposite of what it’s designed to do,’ he said.

He explained that the results, published in the Journal of Biological Chemistry, are very preliminary, but they do point to a need for further investigations into how these medications work.

Type 2 diabetes occurs when cells in the body fail to respond to insulin, the chemical signal that regulates sugar and fat metabolism. This results in high sugar levels in the blood, which if untreated can damage blood vessels and nerves, leading to heart disease, strokes, kidney damage and loss of sight.

Exercise and diet changes can reduce the progression of diabetes if diagnosed early. Over time, however, most people require some form of medication. Treatments available today typically suppress sugar production and encourage the pancreas to release more insulin. This is because in a type 2 diabetes patient, the body often ignores the effects of naturally produced insulin and, in response, produces more blood sugars, a process activated by the hormone glucagon.

Ladd explained that until recently, these medications were the only way to treat the disease before it had reached the stage when patients had to inject insulin themselves. In the past few years, however, a new treatment has emerged that both targets the effects of diabetes and promotes weight loss.

These therapies are based on a hormone known as glucagon-like peptide-1 or GLP-1. When you eat something, the intestine releases the hormone in order to promote insulin secretion. At the same time, it makes the stomach empty itself more slowly and makes people feel full.

‘Unfortunately, GLP-1 breaks down rapidly in the body. So in response, scientists created a number of artificial injectable versions that mimic its effects but last for much longer. While these GLP-1 mimetics have been approved for use and for treating diabetes, they are not without controversy and there is a continuous scientific and moral requirement for clinicians and scientists to evaluate and investigate their effectiveness and mechanism of action,’ said Ladd.

‘Our research found that one such GLP-1 mimetic may, under specific conditions, activate the molecules in the body’s cells that recognise the signal from the hormone glucagon. Were this to happen in the liver, it could promote the release of sugars into the blood, precisely the process that it is supposed to prevent,’ Ladd added.

He acknowledged that the results are likely to prove quite controversial. ‘A limited number of published studies previously suggested that GLP-1 cannot bind to the glucagon receptor molecule at all, ruling out the possibility of this effect. Our research contradicts this. The key difference is that we studied how the treatment was affected by another molecule called RAMP2 that is found in varying amounts around the body,’ he said.

‘We found that without the presence of this molecule, the GLP-1 was able to bind with the glucagon receptor and so promote sugar release. Ramping up the receptors. The problem is that we know very little about RAMP2. In our study, we found GLP-1 only has a limited ability to interact with glucagon receptors. But because the GLP-1 drugs are designed to reside in the body for much longer than the natural GLP-1 molecule, this may increase the chances of interaction,’ he explained.

He also pointed out that another study earlier this year found that prolonged use of the same GLP-1 mimetic in type 2 diabetes patients led to an increase in glucagon secretion, correlating with the results of this study.

‘Our study in no way suggests that GLP-1 mimetics are at all dangerous for patients currently using them. Indeed, the beneficial effects for many patients currently outweigh the risks. But it does not mean that we should not continue to evaluate and investigate this treatment as new information about its interaction with the body emerges,’ he concluded.

The opinions expressed in this article do not necessarily reflect the views of the Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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