August 6, 2010

Lastest Study Touts Benefits of Once a Week Injected Byetta

UPDATE (April 2, 2013): Before you take Byetta, Victoza, Onglyza, or Januvia please read about the new research that shows that they, and probably all incretin drugs, cause severely abnormal cell growth in the pancreas and precancerous tumors. You'll find that information HERE.

Original Post:

In one of those studies beloved by drug companies, three different drug regimens were compared against each other for a very brief period (six months) in a relatively small number of people (about 170 per regimen.)

One of these drugs was long acting Byetta (LAR) which will be marketed as Bydureon if it ever gets approved by the FDA. That hasn't happened yet. While this study is being reported as showing long acting Byetta as superior to the other regimens, what it really showed was that none of them is particularly helpful to people with Type 2 diabetes.

Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial Dr Richard M Bergenstal et al. The Lancet The Lancet, Volume 376, Issue 9739, Pages 431 - 439, 7 August 2010 doi:10.1016/S0140-6736(10)60590-9

As usual, the participants in the study started out with an average A1c of 8.5% which is quite high and suggests that many people in the study had A1cs far higher than 8.5%. Drug companies always use people with the highest possible A1cs in their studies because it is a lot easier to drop anyone's A1c from 10% to 8.5% than it is to drop an A1c from 7% to 5.5%--though the latter A1c is the only one that would ensure excellent health.

The regimens all included metformin, to which was added Januvia (sitagliptin), Actos (pioglitazone) or the long acting slow release 2 mg dose of Byetta (Exenatide.)

The only end point (i.e. thing that would be reported) was change in A1c. As we all know, this can be a misleading statistic because the identical A1c may represent very different patterns of blood sugar performance--and these different patterns have very different outcomes in terms of causing the classic diabetes complications.

In particular, drugs that lower A1c by causing reactive lows in response to high blood sugar peaks will result in higher complication profiles than those that achieve lower A1cs by flattening blood sugar curves.

But to get back to this study, the finding after 6 months was that the group taking metformin and once a week Byetta saw an average drop in A1c of 1.5% compared to .9% for Januvia and 1.2% for Actos.

As the group average A1c started out at 8.5%, these average drops in A1c still left everyone involved with blood sugars high enough to guarantee the classic diabetic complications and heart disease.

You can learn what peer reviewed research has learned about what blood sugar levels cause complications HERE and what A1c predicts heart attack HERE.

This suggests that none of these regimens meets the only endpoint anyone with diabetes really cares about: preventing blindness, neuropathy, amputation, kidney failure and heart attack, all of which become much more likely as soon as A1c goes over 6%.

Participants in this study lost more weight--on average 5 lbs lost with Byetta, compared to less than 2 lbs with Januvia and a weight gain of 6 pounds with Actos.

This finding needs to be put into context. These are averages, and we know that the way Byetta works, one third of those who use it see dramatic weight loss and improvement in their blood sugar levels. The rest experience little or none. So that average--and the A1c average--is probably meaningless, there were most likely 1/3 of the participants reporting much bigger losses and the rest reporting none, a fact that is lost when the data is averaged.

One reason for that impressive weight loss is made clear in the reporting of the side effects. One out of 4 taking Byetta experienced nausea and one out of five diarrhea.

The study was too short in duration and too small in the number of participants to tell us anything useful about long term side effects for any of these drugs. When it comes to side effects, after reading every study published about these drugs, I personally like Byetta better than Januvia or Actos.

Januvia worries me because it turns off the gene that produces the DPP-4 enzyme the immune system uses to kill melanocytes that have become cancerous and which also is involved in fighting ovarian, lung and prostate cancers. (Details HERE.)

I also like Byetta a lot better than Actos, which long term causes what may be irreversible osteoporosis in the arms and legs as well as edema which may lead to heart failure, even in people who had no sign of heart failure at the beginning of the study. (Details HERE.)

But Byetta is still relatively new, so we can't be entirely sure that over a long time it will be harmless, and these diabetes drugs are intended to be used for a lifetime.

The bulk of research we have suggests strongly that Byetta does not in ANY way affect the underlying causes of Type 2 diabetes, though it may, for about 1/3 of those who take it provide significant weight loss and effective blood sugar control. (Details HERE.)

It is because the people for whom it does work experience such dramatic improvements, that I have come to think it might be one of the drugs worth trying. But because it isn't effective for 2/3 of those who take it, if you don't see dramatic results within a month, there is no reason to keep on taking it.

If you are considering Byetta, once the long acting version is approved always start Byetta with the short acting twice a day version.. Try the daily version to see if you are one of the 1/3 of people who respond to Byetta.

The side effects of Byetta can be miserable and you really don't want to put a drug into your body that lasts a week and can cause nonstop vomiting and diarrhea. With the twice daily injections, if the side effects are intolerable, you can just stop using it and they'll stop almost immediately. Many people who do respond to Byetta find that they get over the side effects after starting with the low dose and working up.

That said, before you spring for any of these drugs, remember that most people with Type 2 can drop their A1cs considerably more than 1.5% simply by cutting way down on their carbohydrate intake. You can find instructions on the easiest way to do this HERE.

I hear continually from readers of this blog and of my web site who have dropped A1cs from as high as 13% down to the 5% range simply by cutting way down on their carbohydrate intake. Some have had diabetes for a decade or longer and only learned after reading the Blood Sugar 101 site that it is the carbohydrates we eat at meal times that raise our blood sugars.

As we now have a long term study of the low carb diet that finds zero negative health outcomes in people using it over two years and yet more proof that people on low carb diets end up with better cholesterol profiles than people on low fat diets, there's no reason not to cut as far down on your carbohydrate intake as you can manage comfortably.

Weight and Metabolic Outcomes After 2 Years on a Low-Carbohydrate Versus Low-Fat Diet: A Randomized Trial Gary D. Foster et al. Annals of Internal Medicinevol. 153 no. 3 147-157 Aug 3, 2010. (Discussed HERE.)

Anecdotal experience suggests that most people with Type 2 diabetes can achieve significant drops in A1c by cutting down their carbohydrate intake to 70-110 grams a day, which is much higher than the level used in low carb weight loss diets. This is especially true when they combine metformin with the low carb diet a synergistic combination that often results in the best outcomes.

Lower intakes work even better, but may be harder to sustain by people who have to interact on a daily basis with others in situations where food is an important part of the social behavior.

I have great respect for everyone who can maintain on lower carbohydrate intakes, but my goal is to help people find ways to control their blood sugar that does not require heroic self control and which can be sustained for decades without diet meltdown.

We know for a fact that the low carb diet has no side effects except weight loss of approximately 20% of starting weight for most people, dramatically lowered blood sugar, and improved lipids. None of the pharmaceuticals can make that claim.

6 comments:

country mouse said...

I am definitely one of those exceptions that prove the rule. I did great on a low-carb diet for about nine months then my triglycerides and cholesterol skyrocketed (650/350) and control starts to slip. Fast forward to June and one stent clearing a 99% blocked artery and then after I restart metformin, control doesn't really come back. They put me on crestor and all of a sudden, control gets worse, much worse. I go off and it's back to the postoperative bad level.

Go figure. I'm seeing a new endocrinologist in a couple days so, will see although I don't know what they can do if metformin isn't working, glyburide makes me "decidedly unpleasant to be with" and all the others are just death traps. And I mentioned, I'm really phobic about needles. Took me almost 3 months to be able to stab myself consistently without twitching for blood glucose measurements. I'd probably be an extremely low compliance insulin user.

I know I'll figure something out but, I'm having way too many moments like that.

nonegiven said...

If it helps any, the pen needles they prescribe for Byetta or insulin are pretty small. IME they hurt a lot less than the finger pricks.

nonegiven said...

ps It's my understanding that the once a week Byetta is probably using bigger needles that hurt more than the twice a day kind. I filled out a marketing survey that seemed to be suggesting that, anyway.

Boz said...

Diet, exercise, Lantus, Novolog, Metforman. That's my regimine. I was on Byetta for a while, and it worked somewhat well. But the gastric distress wasn't worth it. After a cortisone shot, Byetta was rendered ineffective, so it was on to the insulin. That has worked well for the last couple of years. But, the best treatment, for me, is diet and exercise. Smaller meals, healthy fats, lower carb intake and no fried foods works well. I'm still having a hard time with weight loss, though.

Jenny said...

Boz,

Most of us have a very hard time with weight loss. I did a poll last year and found that most people with Type 2 stall out at 20% lost from starting weight even on stringent weight loss diets.

The good news is you don't need to lose weight to avoid complications. It's all about blood sugar control.

Diana said...

Byetta made me hypoglycemic, so I had to quit. I didn't mind using it though & wish I could find something similar that worked.

I agree with Jenny...you don't have to lose weight to lower your blood sugar. That is a myth I wish the world would get over ASAP.