A kink in the armor?

A kink in the armor?

One of the bright spots in the diabetes drug space has been the increasing usage of GLP-1 therapy with Type 2 patients. GLP-1 therapy offers several compelling benefits – solid glucose control – simple dosing – no need for the patient to monitor their glucose levels on a regular basis- at worst GLP-1 therapy is weight neutral and more often than not patients actually lose weight – little risk of severe hypoglycemia. Like all diabetes therapies and GLP-1’s are no exception, there are some concerns over adverse events, pancreatitis and pancreatic cancer are the most frequently noted. However, based on all available data most experts agree there is not a causal relationship between GLP-1 usage and these events.

New research appears to indicate that long term GLP-1’s may weaken insulin producing cells and result in increased production of blood sugar. According to a study published in Cell Metabolism the authors concluded;

“In summary, we show that chronic activation of human islets by prolonged daily liraglutide treatment in a humanized mouse model is associated with initial improvement in function that is followed by progressive deterioration over time. These findings are consistent with the notion that “excessive” activation of an already-overworked β cell under diabetic conditions during long-term treatment with incretin mimetics may lead to metabolic exhaustion of the β cell (Araki et al., 2003, Larqué et al., 2011) and, ultimately, compromised glucose homeostasis. This is conceptually important to consider prior to prescribing long-term, multiyear, continuous usage of GLP-1 analogs for the treatment of T2D.”

“Given the lack of clinical studies on the long-term effect of these drugs in diabetes patients, this is a very important discovery,” said Diabetes Research Institute researcher Midhat Abdulreda from the University of Miami Miller School of Medicine.

Study author and Karolinska Institutet professor Per-Olof Berggren said it is vital to consider these findings prior to the prescription of drugs with GLP-1 equivalents, especially in long-term therapies for diabetes patients.

Given this is the first study to examine this subject combined with growing usage of GLP-1’s we suspect this is not the last we will hear about this subject. This study also brings to mind something we have said many times – there is no such thing as a completely safe drug and when it comes to diabetes therapies in particular, therapies which are used over many years, not all adverse events will be identified during the clinical trial process. Remember it took more than 7 years before we learned of the increased risk of bone fractures for patients taking Avandia or Actos.

The strange aspect of this study is it contradicts other studies which noted that GLP-1 usage actually preserved beta cell function. So the question becomes who’s right here. Hence the reason once again we will likely be bombarded by even more studies on the subject. Once again researchers will debate the data. Once again physicians who are prescribing GLP-1’s more and more will be left to wonder are they doing by the patient.  And of course patients won’t be able to get a simple answer to what seems like a very simple questions; “Are the drugs I’m taking safe?”

Will we find out as did with Dr. Nissen’s now debunked meta-analysis, that this study is flat wrong. Or will real data and not fuzzy math show there is true cause for concern. To be honest Diabetic Investor is not optimistic we will ever get a definitive answer on the subject. This as we note frequently is the nature of the beast.

While we’re sure these researchers had good intentions with this study we can’t help but wonder if the real goal was to create demand for even more research. Or as Roseanne Roseannadanna used to say “It’s always something.”