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BLOG: February 2008
Diabetes drugs, side effects
Drugs used in diabetes two treatment, just like any other drug, have possible adverse side effects. Those used in the ACCORD study were insulin, older diabetes drug Glucophage, as well as new diabetes drugs, Avandia and Actos. Here is the summary of what was known beforehand about the risks associated with them.
It is known that insulin injections produce only temporary benefit in diabetics, due to related weight gain and increase in insulin resistance. In order to keep insulin injection beneficial, the dose has to be constantly increasing. The consequence is significant weight gain, one of the major cardiovascular risks. Participants in the intense arm of the study were receiving
up to four shots of insulin a day,
compared to a standard single shot.
Avandia and Actos both have long history of suspicions and warnings of causing increased cardiovascular risk. Starting with the very beginning,
1999: the manufacturer, GlaxoSmithKline, was accused of trying to intimidate doctor questioning Avandia's safety (New York Times),
2002: internal FDA memo warning about post marketing reports of the two drugs causing heart failure (Public Citizen),
2003: government-sponsored research finding that all three, Glucophage, Avandia and Actos were inappropriately and increasingly prescribed to patients with heart failure (JAMA),
2006: recommendation of then FDA drug safety supervisor Dr. Rosemary Johann-Liang to add black box warning to Avandia and Actos (not only the recommendation was ignored, Dr. Johann-Liang was punished, which resulted in her resignation),
2007: meta-study by Nissen finding that Avandia increases heart attack risk by 43%, with the subsequent FDA's own research confirming it.
This - finally - resulted in a formal official request to add appropriate black box warning for both, Avandia and Actos.
Unlike Actos, Avandia has been found to increase cardiovascular risk even more in those with diabetes. It is probably due to it being more frequently causing fluid retention. Both drugs have weight gain as a common side effects. In addition, their interactions with various cardiovascular drugs are a suspect risk-wise, and still fairly obscured.
Metformin alone did show the capability to reduce cardiovascular risk. At list in part, it can be attributed to it, unlike the other two drugs, not causing weight gain. However, for safety reasons it is not prescribed to those having acute symptoms of cardiovascular disease, and its possible negative interactions with other drugs are not well understood. It is known that when combined with some anti-hypertension drugs (e.g. calcium channel blockers) it can produce hyperglycemia, even loss of glycemic control. Also, it can be dangerous for those with compromised liver and/or renal function.
And, keep in mind,
this is all for standard doses of these medications.
Adverse effects typically increase exponentially with the dose, and participants in the intense arm of the ACCORD study have been receiving
two to three times higher doses of blood
glucose lowering drugs
For some reason, the professionals in charge of conceiving, designing, approving end carrying out this study ignored this glaringly obvious risk factor.
Continues: High blood pressure and cholesterol drugs