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Sunday, August 15, 2010

Byetta--Is it helpful if you are on a low carb diet?

My uncle recently read my handout and says he is following a primal/low carbohydrate diet for the past 10 days but he has not lost any weight.  He is obese and has diabetes controlled well on Byetta--probably a good but very expensive way to control diabetes!!  In addition giving him some diet reminders and telling him to decrease fruit consumption and maybe even counting carbohydrate grams, his question to me was, "Should I stop Byetta?"

I think Byetta has minimal positive metabolic effects If you are on a low carbohydrate diet and you don't really need the extra kick in the pancreas response to control blood sugars.
Byetta is a great medication when diabetics or pre-diabetics are eating the average diet containing  50-60% calories from carbohydrates though.  

The positive effects that would lead to weight loss though are either not needed or can be regulated without Byetta on a low carb diet.  The positive effects that would lower blood sugar aren't needed if the sugar can be controlled on a low carb diet.  Byetta does increases satiety (delays gastric emptying) and decreases appetite/satiety via the effect on thalamic receptors--but a fat and protein rich meal can also increase satiety and relieve hunger.  

Byetta will make the pancreas more sensitive to blood sugar and cause a much higher and quicker  release of insulin.   By suppressing  glucagon release, Byetta stops glycogen in the liver from breaking down into glucose (and discourages the new storage of glucose as glycogen in the liver).   The greater pancreatic sensitivity to blood sugar (and thus insulin release) that Byetta gives though is helpful if you have a "burnt out" pancreas.  It will lead to a quicker control of blood sugar and the appropriate timing of the insulin release.  This beneficial in those advanced diabetes--those with a "burnt out" pancreas with severe dysfunction.

Byetta may not help much on a low carbohydrate diet if you don't have fairly advanced diabetes.  Unless you really need Byetta to control (by enhancing insulin secretion) even the small rise in blood sugar that occurs with a low carbohydrate diet, it seems plausible that this would lead to higher insulin levels than are needed to decrease blood sugars and prevent the toxicity of high blood sugars.  Higher insulin levels even with a normal blood sugar will lead to less lipolysis (net fat storage).   If you have pre-diabetes or easily controlled diabetes (hemoglobin A1c < 7.5 on Byetta and/or metformin), changing from a conventional high carb diet to a low carb diet will likely lead to at least as much benefit as Byetta.  It is my opinion that Byetta may not improve blood sugars or lead to more weight loss when added to a low carbohydrate diet unless the patient's diabetes is advanced.

I'd welcome comments from patients and doctors on the additive benefits of Byetta to a low carbohydrate diet, if any.


  1. Well, as an endo, I have a problem with the minimal metabolic effects quote. Current research states GLP-1 agonists are promising when it comes to decrease LDL/TG, improve HDL, REGENERATE PANCREATIC BETA CELLS (proven). 2nd, while Byetta does enhance insulin secretion, and increases satiety by slowing gastric emptying, it doesn't improve insulin sensitivity at all--it's released when there is sugar in the system and helps w/ insulin release. This comment Leads to my 3rd point: it does not help those whose pancreas is burned out, which is why the FDA does not approve it in those who are insulin dependent (any T1 or insulin dependent T2). Diabetes is a slowly progressive disease. Multiple studies show that LIFESTYLE (diet and exercise) FAILS after a max 7 years even with clean living. BG starts rising again after 3-7 years because those dead beta cells don't come back. So my unsolicited advice to your uncle? Eat right (moderate carbs, not to exceed 135 grams per day--lower amounts can lead to ketoacidosis whish despite what Dr. Adkins said, is actually quite bad for you) BUT STAY ON THE BYETTA-- it may save him from having to go on insulin in the future.

  2. Melanie, I hope to convince you that a 50-100 gram carbohydrate restriction a day is both safe and effective for type II DM and metabolic syndrome.
    In the DPP, lifestyle at 3 years did decrease risk of DM development by 58%. Lifestyle was a low fat diet and exercise (150 min per week) with a goal of 7% weight loss. 58% decrease in DM at 3 years. If a lower carb diet was the diet intervention, one might expect even better results, as multiple studies have shown that even at 1-2 years, HDL, TG, blood pressure, insulin levels, etc are significantly improved on a low carb diet compared to a low fat diet--even in studies that show weight loss is ultimately equal at the end of the study. See the 2008 review of relevant studies http://www.nutritionandmetabolism.com/content/pdf/1743-7075-5-9.pdf and the Ornish/Learn/Atkins/Zone 2007 JAMA article JAMA. 2007;297(9):969-977 a trial including the mediterranean diet, N Engl J Med 2008; 359:229-241, N Engl J Med 2003; 348:2082-2090 and the most recent 2 year trial, Ann Intern Med. 2010;153:147-157. Maybe with the improved blood sugars, insulin levels, and HOMA-IR.

    Of note in the study including the mediterranean diet, the mediterranean diet beat the low fat diet in HOMA-IR and insulin levels among diabetics while the low carb did not, but the distribution of diabetes and severity between groups at baseline was not at all equivalent in the diabetic subjects (2 insulin treated patients each in the low fat group and low carb group and none in the mediterranean group). The HOMA-IR and insulin look significant in the non diabetic group on the graph (bars not intersecting) but P values were not reported. I think more significantly though, from their results section:
    "Among the participants with diabetes, the proportion of glycated hemoglobin at 24 months decreased by 0.4±1.3% in the low-fat group, 0.5±1.1% in the Mediterranean-diet group, and 0.9±0.8% in the low-carbohydrate group. The changes were significant (P<0.05) only in the low-carbohydrate group (P=0.45 for the comparison among groups)."

    When I mentioned burned out pancreas, I just meant ineffective enough to not manage enough of an insulin release after a low carb meal to control blood sugar, not completely burned out as in on insulin so insensitive/overworked to need sulfonylureas.

    My point regarding Byetta is that the positive changes (including dec TG, inc HDL, weight loss etc) are very similar to the well proven changes of the low carbohydrate diet effects and that Byetta may not be adding very much, or at least it has not been studied that I know of in this dietary setting. Also, the beta cell preserving effects correlate with lower insulin levels, better A1c's, and HOMA-IR seen on a low carb diet.

    I don't mean to argue, I just think we need to really rethink our dietary advice. I really hope for the third of Americans that have or are at high risk of developing DM that we try and prevent and reverse DM before the inevitable addition of multiple oral agents then a never ending insulin titration.