Here is some information I found on this subject x x
Byetta
Byetta is one of the most over-hyped new diabetes drug to come along in years. Claims for it include massive weight loss without dieting, normalizing blood sugars, and regenerating beta cells.
Needless to say, the truth about it is more complex. Still, if you have type 2 diabetes, it would be worth giving it some attention.
What Byetta Does
Byetta is a substance that mimics a kind of hormone called an "incretin hormone" which is secreted by cells in the gut when people eat. GLP-1,is one of these incretin hormones. And its functions include stimulating the secretion of insulin when blood sugars rise and controlling the values that cause the stomach to empty food into the small intestine. GLP-1 passes into the brain, too, where it has effects on eating behavior and other metabolic functions that are not well understood.
Byetta is a molecule that is similar to naturally occurring GLP-1, however, changes in its molecular structure make it not break down as swiftly as naturally produced GLP-1, so its effects are longer lasting.
The original molecule that formed the basis for designing Byetta was found in the spit of Gila Lizards, hence Byetta's nickname of "Lizard Spit."
Byetta is injected and its half-life in the body is about two and a half hours, though some Byetta will remain as long as ten hours after injection.
In the context of treating diabetes, Byetta does two main things. It keeps your stomach valve from opening, which produces a feeling of fullness, and, in some people, it stimulates the beta cells in the pancreas to produce insulin as blood sugars rise after eating.
Delayed Stomach Emptying
When your stomach doesn't empty you feel full. When you are full, you don't eat. When you stop eating 100 grams of carbohydrate at each meal, your blood sugar drops. When you stop eating 1500 calories at each meal, your weight drops. Nothing magic here.
Byetta causes the valve that opens the stomach so food can pass on into the intestines to shut down, sometimes for hours. This makes it physically impossible to overeat.
Byetta's effect on the stomach is probably the major thing it does for many of the people who find it helpful. That's what my endocrinologist has told me, and that's what many people using it report. It stops people from eating, and if overeating is contributing to their high blood sugars and weight gain, the drug will reduce both. Eating rocks would do the same thing, but not as safely.
Over time, however, with Byetta this effect appears to wear off as does its effect on weight loss. This is clear from the studies cited in the prescribing information.
Because of the delayed stomach emptying, people may also see wonderful numbers when they test after a high carb meal without realizing that the food has not yet been digested. If you take Byetta, you need to test your blood sugar a few hours after you'd usually test it, to make sure that when the stomach finally releases the food into your gut you don't see a sudden blood sugar spike.
People posting about their experiences with Byetta on alt.support.diabetes report that they see the peaks they used to see at 1 and 2 hours at 3 and 4 hours. If those 3 and 4 hour peaks are over your target safe blood sugar, any improvements you are seeing at 1 and 2 hours may be illusory.
Improved Glucose Response
However, in some people, Byetta also stimulates the pancreas to release insulin in a natural manner when food is eaten. The sulfonylurea drugs like Amaryl and Glyburide stimulate insulin release too, but they stimulate constantly. Byetta, unlike the sulfonylurea drugs, only stimulates the pancreas to secrete insulin when the blood sugar starts to rise after a person has eaten a meal containing carbohydrates. This means that it isn't likely to cause hypos the way that the sulfonylurea drugs do.
A subset of people
taking Byetta report dramatic changes in their metabolisms, even complete normalization of their blood sugar by Byetta, which allows them to drop their other medications.
These reports are anecdotal. The studies reported in the Byetta Prescribing Information showed Byetta achieving only about a .5% decrease in A1c (i.e. from 7.5% to 7%.)
on average. That said, I have run into several of these "anecdotal" successes online, and their enthusiasm is hard to ignore.
What are the Characteristics of These "High Responders"
Quite a few people who report the dramatic response to Byetta were in good control to start with. Unlike the people in the studies cited in the Prescribing Information, they started out with A1cs nearer 6% than 8%. That may be significant.
Several of them also are Jewish. This may also be significant, because we know that there is a genetic found among people with Type 2 diabetes who are of Ashkenazi Jewish descent or from certain nordic populations, such as Danes and Finns, defects the P2 promotor region of HNF-4a gene, which has recently been linked to elevated secretion of hepatic glucose. It turns out that GLP-1 also suppresses glucose production by the liver.
Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic effect. Ronald L. Prigeo et al. 285: E701-E707, 2003.
June 2007 Study Confirms Byetta Works Great for a Few But 70% of Those Taking It Experience Damagingly High Blood Sugars and Little Weight Loss
A manufacturer-supported study presented at the June 2007 ADA Scientific Session has been touted as if it proved that Byetta is great for people with Type 2 diabetes--and that's how the press is playing it.
BYETTA(R) Study Showed Sustained Blood Glucose Control Over Three Years in People with Type 2 Diabetes
But read further and you'll see how sad the results of this study really were.
Byetta Produced Dangerous Blood Sugar Levels in 70% of those taking it.
The press release brags:
After three years of BYETTA treatment, 46 percent of study participants achieved the American Diabetes Association's recommended target A1C of 7 percent and 30 percent of participants achieved an A1C of 6.5 percent. [emphasis mine]
This means that fully
7 out of 10 of those taking Byetta had blood sugars high enough to damage their organs for the full 3 years of the study.
The American Association of Clinical Endocrinologists' (AACE) target of 6.5% which these people did NOT attain is the minimal level at which people with Type 2 diabetes are less likely to develop retinopathy, kidney failure and nerve death leading to amputation. And the 6.5% A1c isn't ideal, as it still represents a higher risk for heart disease than a 5% A1c would be.
The ADA's 7% A1c target is helpful for people with Type 1 diabetes, but the major study of people with Type 2 diabetes, the UKPDS, found that maintaining a 7% A1c only reduced microvascular complications in Type 2s by 12%--far, far less than it did for Type 1s. In short, a 7% A1c reflects a blood sugar level that is dangerously high for a person with Type 2 diabetes.
So what this study really says is that
seven out of ten people taking Byetta in this study, for three whole years, maintained blood sugars high enough to damage all their organs.Three Year Study Finds Byetta Causes Trivial Weight Loss in Most People,
When patients report that Byetta isn't helping their blood sugars, they are told to keep taking it because it causes weight loss.
But here's what a press release put out by Byetta's maker, Lilly, reports that their
own study found about Byetta's weight loss:
Weight loss from baseline was progressive, with participants losing on average 11.68 +/- 0.88 lbs at three years. In addition, one in four patients lost an average of 28.66 lbs.
What this means is that three out of four people taking this expensive drug that did NOT control their blood sugar lost an average of 11.68 pounds over three years, or not quite four pounds a year. In a group of people who weighed well over 200 lbs each, this is not exactly miracle weight loss.
Does Byetta Restore Beta Cell Function?
This is a huge question, and the drug companies that make this stuff are making this claim based on some very sketchy data.
There is some mouse research data showing that incretin hormones may regenerate beta cells. But when the question is asked, is this happening in people, the only "data" cited to support the claim that Byetta is regenerating beta cells is data showing Byetta improving people's A1c, which doesn't mean that beta cells are regenerating, only that blood sugar control is improving, which you can also achieve by cutting back on carbs or reducing insulin resistance, without having any effect on the pancreas. Since people on Byetta are eating a lot less of everything, including carbs, improved A1cs do not necessarily mean beta cells are growing back.
Unfortunately, there is currently no way to examine the pancreas of a living person without destroying it. Because the FDA allows drug companies to make claims for how their drugs work that are not well supported by peer reviewed data, the drug companies can are allowed to claim that their drugs regenerate the pancreas based only on improved A1cs.
Don't get taken in by this hype until it is much better supported. One finding that suggests that Byetta does
not regenerate beta cells in humans is that in the people who have been taking Byetta the longest, the blood sugar, after improving, reaches a plateau and then starts to deteriorate again. The plateau reached is usually still at a level where the patients have diabetic blood sugars.
If beta cells were regenerating, control should improve as the drug is taken and remain improved when it is stopped, rather than deteriorate. Anecdotally, users report that stopping Byetta usually results in blood sugars returning to their pre-drug state.
The Downside of Byetta
There are several problems with Byetta. Some are well known, and the most troubling one is not.
Byetta Makes People Very Nauseated
About half the people taking Byetta get very nauseated. This is related to its effect on stomach emptying. Some people say this effect can be countered by wearing "Sea bands" which are an acupressure seasickness aid. The other half of people taking it do not have this problem.
Byetta Does Not Work for Many People
If you scan through the many months worth of data at the Byetta blogs at
Diabetes.Blog.com you'll see that there are quite a few people who do not get dramatic results from Byetta and even a subset of people whose blood sugars worsen dramatically after they start it. What is strange is how many people keep taking the drug long after they have seen that it does not have any measurable positive effect.
Byetta Can Provoke Antibodies
A serious problem with Byetta may be that, like any injected protein, it can provoke an antibody response which in some cases can be very strong.
When an antibody is produced it latches onto the molecule that provoked it and keeps it from doing its job. If the molecule is the injected Byetta, that is one thing, but it is also possible that the antibodies Byetta produces may latch onto a person's own home-made incretin hormones and keep them from working, too.
If this is the case, the person might end up in worse shape than before they started the Byetta, because they have deactivated hormones that might have been working until they took the drug.
The information in the Byetta Prescribing Information mentions that antibodies are produced, and that in a small group of people a LOT of antibodies are produced, but there is no further discussion on this, or any further research about it. I have asked several knowledgeable endocrinologists about this problem but they say they only know what I know from reading the prescribing information.
It is possible that production of these antibodies is the explanation for why some people post on the Byetta blog that their blood sugar gets far worse after they start Byetta.br>
You can learn more about the side effects experienced by many people who have taken Byetta at the Diabetes Monitor Byetta Page at:
Diabetes Monitor Byetta FAQ
This information is based on the thousands of posts on the Byetta blog sponsored by this web site.
Does Byetta Cause Pancreatitis? New Evidence Suggests NO
On Oct 16, 2007, the FDA posted a warning about Byetta, saying that they had received 30 post-marketing reports of acute pancreatitis (a severe inflammation of the pancreas which can be fatal) some of which went on to kidney failure. The FDA said doctors and patients need to be alert to the signs and symptoms of acute pancreatitis, which include persistent, severe abdominal pain that can radiate to the back and may be accompanied by nausea and vomiting. The incidence of this side effect appeared to rise after patients moved from the 5 mc to 10 mc dose.
FDA Safety AlertLarge Health Claims Database Analysis Suggests Byetta Does Not Increase The Incidence of Pancreatitis
The people at Medco a huge prescription management company ran a database analysis to answer the question of whether the incretin drugs might be causing pancreatitis and their findings which were presented at the 2009 ADA session are encouraging.
The methodology was to analyze "pharmacy and medical claims from the National Medco Integrated Database."
A total of 123,621 patients were divided into three groups: 9,260 patients were taking exenatide, 2,143 patients were on sitagliptin and 112,218 were in the control group. Patients were followed for 540 days to measure the incidence of acute pancreatitis....A total of 123,621 patients were divided into three groups: 9,260 patients were taking exenatide, 2,143 patients were on sitagliptin and 112,218 were in the control group. Patients were followed for 540 days to measure the incidence of acute pancreatitis.
The finding was that "Only 41 patients (.44%) on exenatide, 6 patients (.28%) on sitagliptin and 438 (.39%) in the control group had pancreatitis during the study period."
While this is a very short term study--less than two years--it looks like the incidence of pancreatitis is not statistically significant compared to controls. Pancreatitis does occur in the general population for reasons not entirely understood.
Because Januvia appears to be a far more dangerous drug for reasons discussed
HERE Byetta is probably the safest of the incretin drugs, and probably safe to take at the lower dose, especially if you discuss the symptoms of pancreatitis with your doctor before starting it.
Do Not Take Byetta If Your Kidneys Are Impaired
In late 2009 the FDA analyzed postmarketing data for Byetta and found 78 cases of kidney failure reported between April 28, 2005 and October 29, 2008, a period in which more than 6.6 million prescriptions for Byetta had been dispensed.
Given the prevalence of kidney failure among people with established diabetes this finding may or may not be related to the drug. The FDA now states that Byetta should not be prescribed to people with "severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease." Caution should be used when prescribing it to people with "moderate renal impairment (creatinine clearance 30 to 50 ml/min)."
Because doctors are ignorant of or ignore FDA drug warnings check your creatinine clearance test results before you start Byetta. If your doctor has not given you this test once a year, find a new doctor. All people with diabetes should have their kidney function tested periodically.
Warning signals of kidney problems are: Increased serum creatinine, Changes in urination (color, frequency, amount), Unexplained swelling in the extremities, Increases in blood pressure, Lethargy, Dull ache in the mid to lower back. NOTE: Changes in appetite and digestion are also listed as symptoms of kidney dysfunction but are also normal responses to Byetta.
FDA Safety Information for ByettaA Sane Strategy
There are other effective treatments for diabetes and if you can get one of them to work for you, it might be better to wait another couple years to see what more we learn about Byetta's effects on the body.
You are going to have diabetes for a long time, so if you can get good control by lowering your carb intake or using a proven drug like metformin or insulin, there's no hurry. In another couple years we'll know much more about Byetta and if it does prove out then, you'll be able to use it safely.
Is Byetta Worth a Try?
Because Byetta does have a transformative effect on some people with diabetes, it may be worth trying if you have not been able to control your diabetes with safer, proven therapies like cutting way back on your carbohydrate intake, exercise, and metformin. The following guidelines should help you use it effectively with the least negative impact on your health.
- If you try Byetta for a month and do not see a sharp improvement in your blood sugar level, or if you see your blood sugar get worse, do not continue taking it, but demand your doctor give you more effective medication. People often take Byetta for many months hoping it will "regenerate" their beta cells when the very high blood sugars they are experiencing are guaranteed to kill any beta cells they may still retain. If you don't believe this, please read up on "glucose toxicity" which describes how high blood sugars kill beta cells.
- If Byetta is having a strong impact on your hunger level and helping you to lose weight, but you are still seeing very high blood sugars, Byetta should be treated as a weight loss aid, but you need to talk to your doctor about what you can do while you lose weight to better control those blood sugar levels.
- If you have not responded to drugs that stimulate insulin secretion like Amaryl or Glyburide, it is less likely that you will get better blood sugar control with Byetta. You may be too insulin resistant for the amount of insulin secreted in response to GLP-1 stimulation to make a difference, or your beta cells may be dead and no longer capable of secreting at all. If that is the case, you might do better with a drug that reduces insulin resistance and insulin supplementation rather than beta cells stimulation.
- If you have not responded very strongly to Byetta, Januvia is not likely to do anything for you but lighten your wallet. Januvia raises naturally occurring GLP-1 rather than providing a supplemental form as Byetta dose, and the natural GLP-1 is much milder in its effect than is Byetta. Because Januvia shuts down an enzyme that plays an important role in the way the immune system fights cancer, it is a very dangerous drug, though doctors have not gotten this message even though it has been discussed in the medical press.
