low blood sugar episodes, measuring blood sugar, Invokana and Farxiga

A week ago the FDA put out a report that “suggested significant or near-significant increases in all-cause mortality” associated with the diabetes drug Onglyza (saxagliptin). In other words, more patients died while taking Onglyza than taking placebo. In addition, the FDA noted that there was an increased likelihood of hospitalization because of heart failure in those people taking Onglyza.


This information was part of an intensive analysis of a huge study called SAVOR (Saxagliptin  Assessment of Vascular Outcomes Recorded). This post-marketing Phase 4 trial involved 16,492 high-risk patients with type 2 diabetes. They were randomized to receive either Onglyza or placebo. The FDA wanted to determine whether there might be adverse cardiovascular outcomes such as heart attacks, strokes or deaths linked to long-term exposure to Onglyza. They were also hoping to discover whether this relatively new diabetes drug might actually prevent such problems.

The Envelope Please!

After roughly two years the verdict is in, and it’s not very impressive. First, treatment with Onglyza did NOT prevent serious heart events or strokes. Presumably that is one of the key reasons for taking a diabetes drug, ie, preventing the worst complications of the disease. The FDA seemed thrilled that the drug did not appear to cause heart attacks and strokes, but we find that a pyrrhic victory in light of the fact that it was associated with an increased risk for heart failure and death.

One might think that such complications would be extremely worrisome. In decades past when a diabetes drug was found to increase mortality it immediately became controversial and lost favor with physicians and the FDA.

The first randomized controlled trial of the diabetes medicine tolbutamide (Orinase) was called the University Group Diabetes Program (UDGP). It was stopped prematurely in 1969 because of an increased death rate in the drug takers compared to those on placebo.

Not surprisingly, the manufacturer of Orinase complained bitterly about the study results. Nevertheless, the FDA sent out alerts and “Dear Doctor” letters notifying prescribers of the risks.

Fast Forward to 2015 & Onglyza

Things at the FDA are quite different 45 years later. A special advisory committee meeting at the FDA reviewed the data from SAVOR and concluded that the drug should not be withdrawn from the market and did not need restrictive labeling. The FDA committee determined that the drug did not pose an unacceptable risk, even with the problems described above.

A similar drug, Nesina (alogliptin) also got a green light despite a signal that it too could increase the risk for heart failure. The panel did recommend that both drugs carry warnings about heart failure, though how much attention is paid to such labeling changes remains questionable.

There’s big money at stake. Last year Onglyza had sales of $820 million and Nessina topped $400 million. Another drug in the class, Januvia (sitagliptin), has had sales over $4 billion annually.

Dr. Sidney Wolfe of Public Citizen, a consumer advocacy organization, commented at the hearings that Onglyza has no unique benefits but some unique risks. He recommended that the drug be recalled.

Heart Failure

Heart failure may sound somewhat innocuous, but in fact it is a very serious complication. Not only can heart failure be lethal, but in people who don’t die of it right away, heart failure can seriously impair quality of life. The shortness of breath, difficulty exercising, lack of energy and swollen legs and feet can be extremely uncomfortable as well as disconcerting.

Heart failure is also hard to treat. Although physicians may prescribe a range of medications, often several drugs are needed to counteract the problems heart failure causes. In some severe cases, the person may need to have a device implanted to help the heart mechanically. Occasionally, heart failure must be treated with a heart transplant.

The point here is that it is a serious condition that must not be brushed aside. Unfortunately, Onglyza is not the only diabetes drug that can increase the risk of heart failure. Older medications such as rosiglitazone (Avandia) and pioglitazone (Actos) also increase a patient’s risk of developing heart failure. This complication contributes significantly to the cost of caring for people with type 2 diabetes in the US.

Pancreatic Cancer?

There have been indications for several years that one drug in this category, Januvia, increases the risk for a rare but extremely dangerous side effect, cancer of the pancreas. Although the FDA apparently has decided that this is not a significant side effect of Januvia, that may not be the message from the adverse events that get reported to the agency.

If FDA fails to be concerned about the potentially deadly side effects of drugs to control blood sugar, patients will need to watch out for themselves. To the extent possible, controlling blood sugar with exercise, diet and the least dangerous drugs at the lowest dose that works may turn out to be the best strategy for many individuals.

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  1. Jan

    I have had several doctors insist that I am borderline diabetic. They gave me the The first one gave me Metformin and even on a low dose it made me feel sick and I slept all the time. The second one gave me Glipiside. I lasted longer on that but eventually, I began to sleep all the time. When I would complain about these things, the doctors acted like I just wanted to deny I was diabetic. Apparently, my sleeping all the time was better to them than my not taking the medicine. After experiencing these things, knowing I felt fine before taking any medicines for diabetes, I am wondering if doctors are too rigid about the numbers. If I feel better with out the drugs and the doctors insist I should have the drugs, something is not right.

  2. Jn

    maybe we should get the FDA out of the regulation of drugs entirely.
    The FDA is kept out of the vitamin and nutritional industry and that industry is doing very well thank you.
    The American consumer can make their own decisions without big government interference. FDA regulation only protects big pharma.

  3. Helen M
    Modesto, CA

    I am a diabetic and when lifestyle was no longer enough to control my diabetes, I elected to go to insulin. When metformin came along, I was pleased that it worked well and the digestive side effects also worked in my favor: cured my lifelong problems with constipation. I also tried actos, and gained a lot of fluid and weight; went to avandia: that was worse. So back to insulin and met, until I developed cancer in both kidneys. Then just insulin. With more changes to my diet; going more green, incorporating leaves into every meal, I have worked my insulin usage down to around 20 units a day. I had to see a lymphedema massage therapist to get rid of the fluid; 40 pounds off. Diet took off more, I am down another 25. Heart disease runs in my family, including a sister and both parents; at 77 I still have nice clean arteries and a well functioning heart. After diabetes for over 30 years. Diabetes is no longer a death sentence, if you work at controlling it. Nor, for that matter is cancer; I am a four time cancer survivor.

  4. cpmt

    I am diabetic (2 )and I need help from anyone who knows or has information. I was prescribed LANTUS 5’S and I will like to know if there is any possible side effects or any problems or where can I get this information ? Also the doctor wants me to use Lipitor for blood pressure (which I don’t have but they say I need it for my kidneys), but I can’t handle it, have many problems with it and I was wondering if there is any other similar medication with less side effects and/or possible problems. Many of the old medications worked well but not many are used today (not enough $$ benefits), maybe any of you can advise or tell me which one will be better Any sugestions please? Thank you.

  5. J. David Auner
    Springfield, MO, USA

    Heart failure – well any failure, seems bad. A better name is needed than heart failure. Uncontrolled diabetes acts as a diuretic through osmotic effects. Controlling diabetes in any way frequently uncovers a weak heart muscle. Almost any diabetic needs an ACE or ARB to control afterload on the heart and protect renal function. Some diabetics will need diuretics in addition to help the diabetic heart function. I suspect there is a money play behind this publicity of a mediocre study. I have decades of experience controlling diabetics in the face of poverty, poor nutrition and lack of insurance – I am not impressed by this campaign among others.

  6. Beach Boui
    Eastern NC

    This clearly is further evidence that the FDA has completely abdicated it’s responsibility to the American public, in favor of assuring themselves cushy little jobs with the drug manufacturers once they retire from the FDA. Is there no oversight over these rogues? This article should be an eye opener to every who reads it, and a clear confirmation that you MUST take responsibility for your own heath. Big pharma is clearly driving the boat… not our taxe-paid officials of the FDA. This is sickening.

  7. Barbara K.
    Spartanburg, SC

    I thought that diabetic drugs were to help us control not kill us with heart disease… I was on Advandia years ago and within four days had two swollen legs from knee down.. doctor wanted me to continue and take a water pill.. forget that. Years later they talked me into Actos, even the nutritionists said great drug. So I started ACTOS and within 12 month I had swollen legs up to my hips.. now I have the lower part of leg badly scarred with sort of an orange and brown skin now due to swelling stretching all.. stuck with it now for life.

    I am on Metformin and glucotrol.. only and I will remain on them until……. I have added cinnamon bark from health food store and I do see a lowering of blood readings.. will take awhile to see what it does to the A1C.

    All these companies are out for is money as you noticed you mentioned even how much money Januvia makes. Is this what medicine is for MONEY.. or is it to help us with diabetes with PROPER medication and help. Getting more and more disgusted with medicine ..

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