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Sulfonylureas Lose Again
December 9, 2009
Many people with diabetes have complained about the sulfonylurea drugs for years because these medicines encourage weight gain and can cause hypoglycemic episodes (lows). Now a large study from the United Kingdom has found that, compared to metformin (brand name Glucophage and others), sulfonylurea drugs are associated with higher risks of death and heart failure.
Sulfonylureas act by pushing struggling beta cells to produce more insulin. The increased insulin lowers blood glucose, creating the risk of lows. Their effect on glucose cannot be calculated as accurately as the effect of injected insulin. And they are thought by some people to wear the beta cells out, so you’ll eventually need insulin anyway.
There are two widely used “generations” of sulfonylureas. (A third was more recently developed.) First-generation sulfonylureas were developed in the 1940’s and became available in 1955. They include chlorpropamide (Diabinese), tolbutamide (Orinase), and tolazamide (Tolinase). Second-generation drugs came on-line in the 80’s. They include glipizide (Glucotrol) and glyburide (DiaBeta, Micronase, Glycron, and Glynase).
Second-generation sulfonylureas have been better in many ways. They are more potent and seem to have fewer side effects. But in the UK study, single-drug treatment with first- and second-generation sulfonylureas was associated with up to a 61% increased risk for death compared with metformin. Users of second-generation sulfonylureas had up to a 30% higher risk for congestive heart failure.
The study looked at more than 91,500 British men and women with Type 2 diabetes. They (or their medical records) were followed for an average of 7.1 years. The researchers controlled for sex, duration of diabetes, previous complications from diabetes, peripheral artery disease, cardiovascular disease, other medicines, body-mass index, cholesterol levels, systolic blood pressure, HbA1c, creatinine and albumin concentrations, and smoking status (whew!), so these results look pretty convincing.
In my opinion, the only reason to take a sulfonylurea is if you cannot take metformin, and even then, it’s worth asking about other alternatives (such as insulin or no meds at all). But everyone is different. If you are doing well on a sulfonylurea, you might want to stay on it. Talk with your doctor about your concerns.
And Now for Something Completely Different
This is a huge change from the old belief that “Circadian rhythms” control most body functions. Circadian rhythms help us wake up in the morning and go to sleep at night, for example.
According to the new theory, there is a “master clock” in the brain that responds to light. But there are subsidiary clocks [or "oscillators"] in the other tissues that respond to other factors such as feeding time.
According to Dr. Panda, the liver oscillator is especially important. It “tun[es] the activity of thousands of genes regulating metabolism and physiology,” he says. That means your body will be ready to digest and absorb food, produce insulin if you have any, and produce other chemicals needed to handle food well.
But if the oscillator is thrown off by wildly changing times of food intake, you won’t have the right chemical mix in your blood to benefit from food. The Salk researchers say their findings could explain why “shift workers are unusually prone to metabolic syndrome, diabetes, high cholesterol levels and obesity.”
Of course, if you take insulin, you probably try to eat at consistent times already. But here’s another reason, even if you’re not on insulin. You’ll get more benefit and less harm from your food if you eat according to your body’s internal clocks.
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