The GLP-1 Agonist Debate: How Safe Are Victoza and Bydureon?



GLP-1 agonists are complicated.

Some physicians, such as endocrinologist Dr. Steven V. Edelman, believe GLP-1 agonists, such as Victoza, Byetta and Bydureon, are practically a miracle medication for the treatment of type 2 diabetes. Other physicians, and some researchers, argue there could be significant health concerns associated with the treatment, and that more study is needed to determine their safety. The truth between these two views is decidedly murky, and may require more research to establish.

“There are clear benefits to GLP-1 agonists,” says Edelman, a professor of medicine in the Division of Endocrinology, Diabetes & Metabolism at the University of California at San Diego, and the director of the Diabetes Care Clinic for the Veterans Affairs (VA) Healthcare System of San Diego. “It has proved effective in controlling type 2 diabetes. It aids in weight loss for diabetics—although it is not a weight loss drug—and it does not have hypoglycemia as a side effect.”

GLP-1 is a naturally occurring hormone released in the intestine that stimulates the release of insulin from pancreatic beta cells when carbohydrates are absorbed in the intestine. Additionally, GLP-1 (which stands for “glucagon like peptide”) is also present in the brain, where it acts as an appetite suppressant.

Research, however, raises concerns about the drugs. In February 2013 in the Journal of the American Medical Association a study was published suggesting an association between GLP-1treatments and an increased risk of acute pancreatitis.

“In this administrative database study of US adults with type 2 diabetes mellitus, treatment with the GLP-1–based therapies…was associated with increased odds of hospitalization for acute pancreatitis,” the report concluded.

There was also a report of a link between GLP-1 therapies and an increased risk of pancreatic cancer, according to the charity, Diabetes UK, on their website in June 2013.

The two GLP-1 treatments available are sold under the brand names Byetta and Victoza. The drugs, however, are not very popular with consumers, and are not nearly as popular as they deserve to be, according to Edelman.

“It’s a case of clinical inertia on behalf of doctors,” Edelman says regarding one reason why more GLP-1 prescriptions aren’t being written. “Doctors are slow adapters. It takes years for new drugs to catch on with many doctors.”

Byetta was approved for sale by the Food and Drug Administration in 2005. Victoza was approved for sale in 2010.

Edelman is comfortable embracing new diabetes therapies. That’s not only because he conducted his diabetes specialty training at the famed Joslin Diabetes Center, in Boston and because he is the founder and director of a not-for-profit organization called Taking Control of Your Diabetes (TCOYD), dedicated to teaching people how to improve their diabetes self care. It’s also because he’s had type 1 diabetes for 43 years.

 “I work at the University and I am an opinion leader,” Edelman says. “I attend all the major diabetes conferences and meetings. I’m very well informed, and I have to say, as a physician and as a diabetic, I believe GLP-1 is one of the most significant advances in diabetes treatment in recent years.”

Another reason GLP-1 agonists aren’t yet a staple of diabetes treatment, according to Edelman, is that they have to be delivered by injection. Byetta is traditionally injected twice a day, although a once-weekly version called Bydureon, was launched in 2012.

Despite the improved frequency of the injections, Edelman says type 2 diabetics are not comfortable with the idea of taking an injectable drug when oral medications are an option.

Additionally, because it’s fairly new, most insurance companies do not cover GLP-1 therapies, and the medications are up to five times as expensive as insulin.

The larger, looming reason GLP-1 agonists are not a more mainstream treatment option, however, is safety concerns.

Despite the alarming nature of reports linking GLP-1 agonists to pancreatitis and pancreatic cancer, it is important to note a definitive link between GLP-1 therapies, pancreatitis, and pancreatic cancer has not been definitively proven.

“There is a suggestion of a link in a recent article between use of GLP-1 based therapy, pancreatitis and carcinoma of the pancreas,” Diabetes UK wrote on its website in June 2013. “The research has given rise to some discussion among specialists and there is consensus that the research findings, though interesting, have limitations.

“Therefore, currently, there is no proven link between the use of GLP-1 based therapies and pancreatic cancer.”

Edelman likewise stresses that an “association” is not a link.

“Pancreatitis and pancreatic cancer are associated with it,” Edelman said referring to GLP-1 therapies. “And it’s not a strong association. The FDA has said that there is no direct cause and effect relationship between (GLP-1 therapies and pancreatitis or pancreatic cancer).”

The American Diabetes Association agrees there is not a conclusive link between GLP-1 and pancreatitis and pancreatic cancer. The organizations also suggests, in a report in the May 6, 2013 issue of its medical journal Diabetes Care, that more research is needed to determine conclusively what potentially hazardous effects the therapies and how to proceed with GLP-1.

“… over the recent past there have been concerns reported regarding the long-term consequences of using such therapies, and the issues raised are in regard to the potential of both classes to promote acute pancreatitis, to initiate histological changes suggesting chronic pancreatitis including associated preneoplastic lesions, and potentially, in the long run, pancreatic cancer,” Diabetes Care Editor in Chief William T.C. Efalu, MD, wrote in an introduction to the May 6 article. “Other issues relate to a potential risk for the increase in thyroid cancer. There is clearly conflicting data that has been presented in preclinical studies and in epidemiologic studies.”

The authors of the report concluded that the onus of proving the therapies safe now rests with those who are proponents for their use: The safety of the GLP-1 therapies can no longer be assumed, and there will be rapid developments in this area. Drug safety can never be assumed, and the legal principle of “innocent until proved guilty” does not apply. The case presented here does not prove that these agents are unsafe, but it does suggest that the burden of proof now rests with those who wish to convince us of their safety.”

Meanwhile, Edelman is optimistic that GLP-1 therapies may eventually benefit people with type 1 diabetes. Although using GLP-1s and insulin is off label, Edelman says studies are emerging suggesting they might work well together and provide benefits to type 1 diabetics, as well.

“This therapy has a future,” Edelman says, “and I’m looking forward to seeing it.”

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7 years ago

Well ucla school of medicine did an examination on diabetic cadavers who were organ doners. I used to take victoza, I puked every day for a month, the gastroperisis was so severe it left bezoar still in my gut after 14 hours of fasting. I was told the sharp abdominal pain was likely from the pertussis and pneumonia I had, but now I question that assesment. I believe it was acute pancreatotis. Of the small sample of cadavers who used glp1 agonist or npp4 inhibitors, every last one of them had an enlarged pancreas with 40 pct. Showing precancerous formations… Read more »

8 years ago

I am 35 and also a Type 1 Diabetic on an insulin pump (since 1995). I just started taking a very low dose of Victoza last Wednesday. It’s day 6 and I have already noticed an amazing difference in my sugars. Believe it or not, I haven’t had any spikes. I’m anxious to see what this upcoming month will bring. No side effects yet, hopefully this continues. However, I am VERY concerned about the warnings of pancreatic and thyroid cancer. Is it really worth it? 

8 years ago

I am using Victoza as a type one and my A1C on the 1.2 dose went from 7.8 to 6.4 and I mostly was using the .6 dose and inched my way up. I am expecting an A1C in the 5% range somewhere. I have more energy and am not having wild swings. I am on an insulin pump.

Alex O'Meara
8 years ago

Jen – I would like to talk to you for a follow-up article about type 1 diabetics using type 2 treatments. If you’d like to, please contact me at Thanks!

8 years ago

I have type 1 diabetes, and I take Victoza, Lantus, and Humalog.  Victoza has been extremely helpful to my diabetes management.  My A1C has been 5.3-5.4% since starting Victoza a little over two years ago.  I will say that I take a smaller dose than what was originally prescribed due to the gastrointenstinal side effects that I experienced at a higher dose.  My understanding is that Victoza is most helpful to adults with type 1 diabetes who were diagnosed as adults and still make some insulin. 

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