May 1, 2009

New Study Proves Conclusively Byetta Does Not Regrow Beta Cells

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:

A study published in this month's Diabetes Care is titled in a way that makes it sound like Byetta "improves beta cell function."

But if you read even the abstract you will see that "improving beta cell function" is NOT the same as rejuvenating beta cells--the claim that the drug manufacturer has been making for Byetta ever since it was released. In fact, what this study proves is the exact opposite: . While Byetta causes more insulin to be secreted in people who are taking the drug, this effect ends as soon as the drug is discontinued.

Here's the study:

One-Year Treatment With Exenatide Improves β-Cell Function, Compared With Insulin Glargine, in Metformin-Treated Type 2 Diabetic Patients. A randomized, controlled trial Mathijs C. Bunck. Diabetes Care 32:762-768, 2009

What they did here was this:
Sixty-nine metformin-treated patients with type 2 diabetes were randomly assigned to exenatide (n = 36) or insulin glargine (n = 33). β-Cell function was measured during an arginine-stimulated hyperglycemic clamp at week 0, at week 52, and after a 4-week off-drug period.
What they found was:
Treatment-induced change in combined glucose- and arginine-stimulated C-peptide secretion was 2.46-fold (95% CI 2.09–2.90, P < 0.0001) greater after a 52-week exenatide treatment compared with insulin glargine treatment. Both exenatide and insulin glargine reduced A1C similarly: –0.8 ± 0.1 and –0.7 ± 0.2%, respectively (P = 0.55). Exenatide reduced body weight compared with insulin glargine (difference –4.6 kg, P < 0.0001).

This means A1c didn't change on average in people using Byetta compared to those using Lantus., though they were secreting more insulin. However, on average, weight decreased significantly in the Byetta group compared to the Lantus group.

But here's the kicker:
β-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period. A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy.

After a year of use, once people stopped taking Byetta their beta cell function went right back to what it had been. Obviously, had their beta cells been rejuvenated, we would have expected to see improved insulin production even without the Byetta. And as most of us would have predicted, losing weight doesn't appear to have changed their ability to control their blood sugars either.

There's an important point to keep in mind here. If you'll remember, and earlier study showed that averages are very misleading when evaluating Byetta's performance. Byetta works very well for about 1/3 of those who take it and barely at all in the rest. You can read about that study HERE.

Dctors have been prescribing Byetta to people who do not experience significant weight loss or improved blood sugar control because they believe it is rejuvenating their beta cells. This claim was based on test tube and rodent studies and has never been confirmed by any human studies. All human studies, like this one, evaluate "beta cell function" simply by seeing how much insulin the beta cell is pumping out in response to a stimulus. Byetta, like the sulfonylurea drugs, does improve the beta cell's ability to secrete insulin, while Byetta is in the system.

But this new study should make it clear that if you aren't one of the lucky people who respond to Byetta with dramatic improvements in blood sugar and weight loss, there is no reason to keep taking it.

Still, over the past two years I have heard from friends who have tried Byetta and have experienced near "miracle weight loss" and dramatic decreases in their need for injected insulin even when eating meals with up to 40 or 50 grams of carb. Some of these are people who required insulin even while eating low carb diets.

So my feeling about Byetta is that it is well worth a trial. Give it two months. If you don't see weight loss and significant improvement in your blood sugars, there is no reason to continue with it.

What disturbs me is how many people I hear from whose doctors insist they continue Byetta when their blood sugar deteriorates while taking it and they don't see weight loss. If that's your situation, you will want to use insulin instead.

It's also worth noting that while Byetta is not officially approved for people using insulin, I have heard from quite a few people who are using that combination successfully. If you combine the two you will probably need to lower your insulin dose other wise hypos are likely.

It's also worth noting that the mechanism by which Byetta was supposed to be rejuvenating beta cells is the same mechanism used by the other incretin drug, Januvia, for which the identical claim is being made. This new study suggests that Januvia is not regenerating beta cells either.


The Old Man and His Dog said...

I'm using Byetta with 32 units of Lantus and Met. Works like a charm. My A1C went from 9+ to 6.1 in six months. I also lost about 35 lbs.. But having said that Even I realize it doesn't work for everyone. I also practically had to beg my Dr to put me on it as she wanted me to continue to take Januvia instead, even though it wasn't working at all. don't know why the Byetta works so well for me when the Januvia did nothing, but that was the case.

Jenny said...

Here's why Byetta works when Januvia doesn't: Januvia only works if your body is producing significant amounts of GLP-1 on its own. It only works by keeping the body from destroying GLP-1.

Byetta is synthetic GLP-1, so it doesn't matter if you make it on your own or not.

Byetta is much, much stronger than Januvia in most people.

Lynn said...

I was diagnosed almost 2 years ago with an A1c of 14. Tried every treatment, starting with Metformin and then Avandamet. (Ugh...)

With the Avandia scare, I demanded to be taken off Avandamet. What a struggle to have a doctor listen! She gave me an alternative of Actos (just saw your previous post this week) but I requested and received a prescription for Byetta.

The weight loss was immediate. I lost a little over 40lbs in 5 months, actually getting too thin.

However, I still couldn't control BS even with a low carb diet (under 50 carbs daily). I switched to Novolog and Levimir and immediately have tight control. Now unfortunately the weight is returning, about 20 lbs in 9 months. When I've mentioned to my doctor about using a combination treatment, I was told Byetta and Insulin can cause significant health issues and that several people have been hospitalized because of it.

As with every other diabetes treatment and diagnosis I've had to fight for, guess I'll need to research this further. First it was demanding to get off Avandamet. Then being diagnosed properly.

It was because of your post about LADA that I was finally correctly diagnosed with Type 1 after a year of being treated for Type 2. At 50 and needing to lose weight, doctors just assumed I was Type2 and didn't believe me when I couldn't get my readings below 200 even with low carbs. The C-Peptide test confirmed the problem.

It's a shame it has to be such a struggle to get the correct diagnosis and treatment and that there aren't more doctors like Dr. Bernstein.

Thanks Jenny for your great work. Awareness is the foundation for achieving good health. You provide that.

Jenny said...


You should ask what the significant health problems were. The main one I am aware of is hypos. Which happen because doctors don't teach people how to test or what the relationship is between blood sugar and the carbs they eat.

Plenty of people are taking the combo, so perhaps you need to find a new doctor. At least your doctor should have suggested Symlin which is appropriate for people taking insulin with Type 1 diagnoses and has a very weak effect similar to Byetta.

Anonymous said...

Jenny, this study's hypothesis never claims beta cell "rejuvenation". Beta cells are not regrow able- once they apop and die they are dead for good. Regeneration rejuvenation and regrow are not terms to toss around presumptuously. Rather the scientific community appropriately and consistently uses terms like preservation, sparing and function. A final point- functional improvement of beta cells stop when the drug therapy stops. Is there a single drug on the market that continues to work once you stop taking it? As always I am grateful for the service you provide hundreds of patients and hope my perspective is not taken as an attack or offense.

Jenny said...

Hundreds of people have posted on web discussion boards that their doctors told them to take either Byetta or Januvia even though these drugs were making no difference in their blood sugar control. The reason? Because they would regrow their beta cells.

This is the pitch the salespeople have most definitely been giving doctors based on cherry-picked research data.

Anonymous said...

Jenny, what about the touted effects of exenatide to reduce pancreatic release of glucagon and to reduce liver fat, both of which I have? As an asthmatic and sufferer of chronic sinusitis, I frequently have a lot of inflammation, which can raise my bs 20-30 points at all times. I eat very low carb; have an A1c of 5.5% and have lost 60 lbs to a BMI of 25.9. You had mentioned a while back you would post about reducing inflammation, still interested in hearing about your ideas there.

Jenny said...


The drug that reduces liver fat and decreases liver glucose is metformin. I'm not remembering that Byetta claims to do this.

The best approaches for limiting inflammation seem to be Vitamin D, oil based, 1-5,000 units a day. Ideally you should have your Vitamin D levels checked first to figure out the right dose so you don't over do it. And fish oil.

Most of the other "natural" herbal products that are supposed to lower inflammation do it because they contain salicylates. You pay a lot of money for them and basically get aspirin.

Trinkwasser said...

It's my belief that mice are designed to have "reversible" diabetes: they can switch rapidly between high insulin food stashing mode and low insulin fat metabolism mode, which probably explains why they are "cured" so easily.

Humans lack the ability to switch modes. This may be why beta cells appear to regrow in mouse studies and the same doesn't occur in humans.

Well technically I suppose individual cells are dying and being replaced on a regular basis but the ability to grow more betas is outrun by the destruction processes in diabetes, and probably also in prediabetes. I believe nondiabetic obese people seem to be able to increase beta cell mass alongside body mass.

Jenny said...

That's an interesting idea about the mice, and makes total sense.

My understanding is that normal people are able to grow as many new beta cells as they need. But also it is looking like the common Type 2 diabetes drugs cause defective insulin secretion and possibly limit the number of beta cells from birth, so that people have a lot less margin even were they to grow new cells.

I saw a very interesting piece about the role of something called microRNA in beta cell reproduction, this is yet another piece of the genetic machinery, recently discovered, and one that people with Type 2 appear to have problems with too. I will be keeping a close eye on this topic as it develops.

Anonymous said...

The concept of beta cell re growth is discussed by the researchers in this study. These were "juvenile" mice and as compared to both adult mice and humans, have much better rates of cell regeneration. Adults (independent of hyperglycemic)are no longer benefiting from beta cell reproduction (although adolescent type 2 humans may). That is why it is so important to "preserve" the approx 20% of beta cell function that is left at time of diagnosis, unless of course you are fine with a new lifestyle associated with regular insulin therapy and hypoglycemic monitoring.

Jenny said...

They aren't necessarily preserving beta cells. Since all assessements of beta cells are done by measuring blood sugar or insulin production, it's very hard to know what Byetta is doing to them.

Over time the blood sugar of people using Byetta in the acceptance trials rose.

And since the 2/3rds of people using Byetta who don't respond well to it are running very high blood sugars high enough to kill beta cells via beta cell toxicity, there's no reason to believe anything is being preserved.

There is very solid data showing that treating Type 2s with insulin immediately after diagnosis makes a HUGE difference long term in how their blood sugar control holds up. Even if they stop the insulin after a month.

I use insulin and find it the best of the diabetes drugs, personally. If you understand the relationship between the carbs you eat and the units you inject there isn't a huge fear of hypo, especially not for Type 2s.

The studies with high hypo rates are usually with elderly people who have not been given any diabetes education who are given the outmoded and dangerous "sliding scale" dosing instructions that ignore what they eat.

Trinkwasser said...

Sedge warblers are sparrow sized birds that breed in northern Europe and cross the Sahara to winter in Africa. In order to make this journey they *double* their body weight. They do this quite rapidly by eating plum reed aphids which are high carb insects, stuffed with sugars from the plant sap they suck. Then they burn off the body fat as fuel for the migratory flight.

This is another example of how "diabetes" may have advantages in specific situations. It'd be interesting to know if their beta mass doubles and halves again along with their body mass twice a year.

Ain't it fascinating when you think out of the box?