SGLT2 Inhibitors Heavily Promoted at ADA

The 2016 ADA conference in New Orleans was the showcase for the latest research on SGLT2 Inhibitors. The Diabetes-in-Control team was at the conference and state the SGLT2Inhibitors had over 150 poster presentations on this class alone. The article says they will cover the new research in depth over the coming weeks.

For now, here’s a taste of some of the breaking news from the sessions:

1. Research pertaining to the kidneys was a major topic. Researchers concluded that canagliflozin slows the progression of kidney function decline compared to glimepirde at almost equal glycemic control. This suggests that canagliflozin’s beneficial effect on kidney function is independent of its glycemic effects.
2. Janssen presented results from a Phase 2, randomized study showing glycemic improvements in adults with type 1 diabetes mellitus (T1DM), when treated with canagliflozin (Invokana) plus insulin.
3. Two study results pertaining to AstraZeneca’s Farxiga were presented. In one study, Farxiga was shown to decrease body weight and blood pressure among patients with kidney problems,
4. In the other study, Farxiga was used in combination with a potassium-sparing diuretic. A1C, body weight and blood pressure were reduced, with no significant increase in potassium levels. This reduces the risk for hyperkalemia.

In other news, the results of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results—A Long Term Evaluation (LEADER) trial was major news at the conference on Monday, June 13. The results showed that liraglutide (Victoza), in patients identified with cardiovascular disease, lowered the combined risk of heart attack, stroke and death from cardiovascular causes by 13%. While a reduction in CV risk with a GLP-1 treatment is an exciting development, there’s not a yet any real evidence of a class effect.

Meanwhile, multiple SGLT-2 drugs are undergoing further testing to explore the possibility that SGLT-2 inhibitors as a class can reduce cardiovascular risk.

Amputation Risk Up for Canagliflozin Users

The FDA had continued to issue new warnings for the sodium-glucose cotransporter 2 (SGLT2) inhibitor class of drugs. This last warning for the diabetes drug canagliflozin which has been linked to an increase in leg and foot amputations. Canagliflozin is marketed as a stand-alone drug therapy under the name of Invokana and as part of a combo therapy under the name of Invokamet.

The Canagliflozin Cardiovascular Assessment Study (CANVAS), a 4.5-year research project which will finish up in 2017 is the basis for the latest warning.

Researchers have found a slightly elevated amputation risk among those who took the drug. The rate of amputation was seven for every 1000 patients taking 100 mg of canagliflozin and five for 1000 patients for those taking 300 mg of the drug. Those in the placebo group saw an amputation risk of three per 1000 patients.

There are many 'what if's' missing from the above analysis. What if the amputations were for people that had the highest A1cs? What is the comparison of A1cs between those patients taking 100 mg and those taking 300 mg. I am talking about those that needed amputations and not the 1000 patients in each group.

The article does say there are many questions raised by this study that still need to be answered. For example, a follow-up study did not yield the same increased rate of amputations for those taking the drug. I have to wonder how a follow-up study can be completed before the CANVAS study is complete. Also, FDA regulators are not certain if the drug was what caused the increased amputation risk. Still, out of an abundance of caution, they are warning doctors to watch for possible foot issues with patients taking canagliflozin and for other SGLT2 drugs.

I am writing about several other issues with the sodium-glucose cotransporter 2 (SGLT2) inhibitor class of drugs. Never assume that oral diabetes drugs are safe and many of the latest drugs are still being found to have serious side effects.

Conclusion Results of the Death

We had a meeting with the pastor and were surprised that the woman's parents were present. They told us that their daughter had become very secretive while in high school. She had become pregnant between her sophomore and junior years and because of weight gain, her parents had not found out about it until she lost the child just before school started. After this happened, she would not name the father and basically ignored her parents.

They were surprised that she had told her husband and Brenda and Sue about her diabetes. She was happy that they had tried to help her, but knew when she was unhappy, she would not talk to anyone, not even her husband. The doctor arrived after this and he confirmed that breast cancer may have been the factor that set her off. He had asked her to bring her husband with her, but she had refused and said she did not want her husband to know.

The doctor did not realize that she was possibly suicidal or he would not have told her about her breast cancer until another family member was present. But after talking with her parents, he doubted she would have permitted another family member to have been present. He concluded that they are still waiting for the cause of death so he may have misspoke in stating suicide. He stated that he should have this on Wednesday and asked the parents if the hospital should limit who received the information.

The parents said yes to limiting the release of information and asked if the news could be limited to avoid the newspapers from receiving the information. The doctor said he would try, but the newspapers could not be prevented if they wanted the information. The parents stated that her husband wanted a small graveside funeral for them and his family and no one else and had changed funeral homes because the one had said it would be put in the newspaper against the family wishes.

Several of us agreed this may be for the best and we would not spread the word. Her parents thanked us and I said I would not release my blog until after the funeral and the mother said she would tell Brenda after the funeral if that was okay. We agreed and the pastor spent some time asking us questions and said we are all sorry this happened, but it was not something we could have anticipated or prevented. We thanked him for his time and having her parents available to us and we thanked them for being present and explaining what may have been behind her actions.

Therefore, even though I had wanted to release this the day after the meeting, it may be several days before this is posted.

Are You Receiving the Best Medicare Care?

This is not a simple solution to a complex problem. How do those of us eligible for Medicare know how to find the best insurance solution? This is even difficult for me. Presently, I have Medicare and a supplemental insurance policy. In addition to this, I am also a veteran and have veteran benefits.

At this time, I am able to choose who provides what benefit. This may change if our current President has his way. He has already disrupted Medicare, Part B in a big way and is threatening to do more damage to Medicare. He has also put limits on what the Department of Veteran Affairs can do for veterans.

Nearly one in three American senior citizens choose to get their government-funded Medicare health coverage through plans run by health insurance companies. The rest get Medicare from the federal government. However, if health policy decision-makers assume the two groups are pretty much the same, they’re mistaken, a new study finds.

And basing decisions on that assumption could (I say will) skew the nation’s efforts to improve care, and spend taxpayer dollars wisely, at the end of patients’ lives, the researchers say. That’s when one-quarter of Medicare spending happens.

Writing in JAMA Internal Medicine, the University of Michigan Medical School team drew their findings from data on a representative sample of Medicare participants who died over a 14-year period. They found the two groups differ in several aspects of health and independence in the last six months of life.

Participants in Medicare Advantage plans – the HMO-style plans offered by private companies – were younger and healthier overall than those enrolled in traditional “fee for service” Medicare. They were also more likely to be black and live in cities, and less likely to be poor enough to qualify for Medicaid. Even after the researchers corrected for differences between the two groups based on their ages, wealth, and education, they still found differences.

Medicare Advantage enrollees said their health was better, reported fewer problems performing daily life activities on their own, and had fewer memory and thinking issues than traditional Medicare participants.

Many health policy decisions are made by looking only at traditional Medicare data, says Elena Byhoff, M.D., M.S., who led the analysis as a Robert Wood Johnson Clinical Scholar at U-M.

That’s because it’s easier to get specific information about what care each patient received, and what it cost the Medicare program, in fee-for-service care. Private plans receive a lump sum to care for a population of patients.

When Medicare Advantage was new and covered a much smaller proportion of Medicare enrollees, basing decisions just on traditional Medicare data may have been reasonable, she notes. But enrollment in Medicare Advantage has tripled in the last 12 years, and now 31 percent of seniors have such coverage.

“Potentially, we’re overestimating the severity of illness in studies of Medicare end-of-life care, and evaluations of policy options,” says Byhoff, an internist and health services researcher who worked on this study with John Z. Ayanian, M.D., MPP, director of the U-M Institute for Healthcare Policy and Innovation.

Building on knowledge

Typical studies of end-of-life care use data that the federal Centers for Medicare and Medicaid Services (CMS) make available to researchers and policy analysts. The new study used data from the Health and Retirement Study, based at U-M’s Institute for Social Research. For over two decades, it has tracked the health and other characteristics of older Americans through detailed surveys.

The team obtained data from 9,385 participants who died between 1998 and 2012, just as Medicare managed care options were taking off. They looked at characteristics as reported on the last survey that the participants took. Just over 24 percent of the individuals had Medicare Advantage.

Other studies have suggested that the Medicare Advantage population might be healthier because the coverage is different, and because the plans aren’t as common in less-healthy area of the nation.

But the new study is the first to show such stark differences among those who died -- and Byhoff says she and her colleagues were surprised at just how different the two populations were.

Some studies have suggested that end-of-life care is less expensive in Medicare Advantage. But the new head-to-head analysis suggests that part of this difference may relate to who’s enrolled than with what’s covered and how.

“Medicare Advantage can limit patient options to providers and hospitals within a defined network,” says Byhoff. “Patients in Medicare Advantage plans are also known to be more likely to use hospice at the end of life, perhaps because awareness of that benefit is higher.” Since 2011, CMS has introduced new programs that seek to improve quality and keep cost growth sustainable in traditional Medicare, such as Accountable Care Organizations.

“If we’re going to have a national conversation on end-of-life care and the spending it drives, we shouldn’t only base it on data from two thirds of the elderly population,” says Byhoff. “Future research and policy decisions should be based on complete utilization data from both major parts of the Medicare program.”

Plant-Based Sweeteners May Help Manage Diabetes

When Gretchen Becker poster her blog - Idiotic Headline – on June 11, I was happy and deleted my partially completed blog. Now circumstances are pushing me back to rewriting a blog.

I admit I never expected to have a Certified Diabetes Educator use the term “plant-based sweeteners” in a CDE class. Yes, this was in a diabetes education class and not a nutrition class that my doctor suggested I take, after learning Medicare had authorized this. Just goes to show how gullible CDEs can be. She thought she had something new to impress the two patients in her class.

She referred to the two sweeteners, stevianna and inulin and expected us to swallow it up. I stopped her and asked why she would use the term “plant-based sweeteners when almost every other sweetener was also plant based. She asked what I was talking about. I told her she had her facts mixed up and I would not consider any plant-based sweeteners because this included table sugar and high fructose corn syrup (HFCS).

She asked which plants these came from as if she thought they only came from the table. Even this brought a snicker from my classmate. I said table sugar comes from sugarcane or sugar beets and unless I didn't know something, they are plants. I continued that HFCS is produced from corn and farmers grow many of these plants.

My classmate had a big grin on her face and she said, “He is correct and you have blown it.” She even added, “How gullible do you think we are?” I added that if she had used stevianna and inulin and not plant-based sweeteners, we would not have had this discussion, but you had to use the term plant-based sweeteners, which we cannot accept.

She referred us to the Medical News Today article and my classmate pulled up Gretchen's blog and linked to the EurekAlert site and asked if this was where she had been suckered in to the plant-based term.

The class went from bad to worse when she talked about the goals we needed to set for ourselves as she was talking about the ADA guidelines and we asked her why we would want to promote the diabetes complications when even the American Association of Clinical Endocrinologists used more reasonable goals and even those were somewhat high when compared to what Dr. Bernstein recommends. When she put Dr. Bernstein down, both of us decided it was time to leave and did so without hesitation.

Once we were outside, she showed me what she had in her folder - “Diabetes Solutions” by Dr. Bernstein. I said you came prepared and she commented we both did ourselves good. I added that she apparently has not been out of school that long and may have just passed the CDE test.

At that point, we were at our cars, said goodbye, and left.

FDA Strengthens Warnings for Two SGLT2 Drugs

The US Food and Drug Administration (FDA) has strengthened its drug label warnings about the risk for acute kidney injury that can result from the use of the type 2 diabetes prescription medications canagliflozin (Invokana, Invokamet, Janssen) and dapagliflozin (Farxiga, Xigduo XR, AstraZeneca), according to an agency news release. The revised warnings include information about acute kidney injury and recommendations for minimizing this risk.

These medications are sodium-glucose cotransporter-2 (SGLT2) inhibitors and are used with diet and exercise to lower blood sugar in adults with type 2 diabetes. The dangers are beginning to show now that these drugs have been in use for over two years. I can just about bet there will be other problems come to the fore over the next five years.

The FDA approved canagliflozin in March 2013 and dapagliflozin was approved in January 2014. In these cases, approximately half of the patients experienced acute renal injury within one month of beginning the medication, and some were younger than 65 years. Most improved after discontinuing the drug. Some of the affected patients were dehydrated, had low blood pressure, or were taking other drugs that can affect the kidneys. Some of these patients required hospitalization and dialysis. The FDA believes there are additional cases that have not been reported.

There is no mention of any warning with another SGLT2 inhibitor, empagliflozin (Jardiance, Boehringer Ingelheim) in this FDA communication, but it has not been on the market long enough.

The FDA does advise healthcare professionals to consider factors that may predispose patients to acute kidney injury before starting them on either of the medications. These factors include decreased blood volume; chronic renal insufficiency; congestive heart failure; and taking medications such as diuretics, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and nonsteroidal anti-inflammatory drugs.

Clinicians should assess the patient's kidney function before beginning canagliflozin or dapagliflozin and monitor it periodically after the patient begins either medication. Clinicians should discontinue the medication promptly and treat the renal impairment if acute kidney injury occurs.

SGLT2 inhibitors have also been associated rarely with fractures and diabetic ketoacidosis, and the FDA strengthened the warning with regard to fracture and canagliflozin specifically last September.

Patients who experience signs and symptoms of acute kidney injury should seek immediate medical attention, says the FDA. These can include decreased urination or swelling in the legs or feet. The FDA warns patients that acute renal injury is a serious condition in which the kidneys abruptly stop working and dangerous levels of waste can accumulate in the body.

The warnings do instruct patients not to discontinue their medication without first talking to their healthcare providers because uncontrolled blood glucose levels can develop. Patients are instructed to read the medication guide that comes with their canagliflozin or dapagliflozin prescriptions.

Healthcare professionals and patients should report adverse events or side effects related to the use of these medications to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.fda.gov/MedWatch/report
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the preaddressed form, or submit by fax to 1-800-FDA-0178

We Will Have a New CDE in a Few Months

Last weekend, Tom, Beverly's husband, came to see me, as he wanted to talk about some of the things she had taught him. He was concerned about her being taught so much about the ADA guidelines and not being concerned about lower blood glucose levels that our support group followed.

I told him that she needed to go along with the current teachings as she needed to pass the test and our goals would not help her pass the test. I asked if she was just explaining what she was learning, or actually telling him to follow what she was saying. Tom admitted that he had not thought about that and that she was probably explaining what she was learning to reinforce this and know it for the test.

I told him not to be concerned until she had her certificate and then what she said. He said he would be more careful and try to let her use him for discussing what she was learning. He said at the same time he would remember what the support group had taught him as it had really helped him manage his diabetes. He asked how Allen was doing and what he latest A1c had been. When I said his latest A1c was 4.6, Tom looked at me in disbelief and asked how this was possible.

I asked him if he had heard of Dr. Bernstein and he said no, he hadn't. I said I don't have the book, but if he remembered some of my blogs, I have written about him and his “law of small numbers.” Then Tom said he remembered this now, but where was this from. We went to my computer and I showed Tom his book “Diabetes Solutions” on Amazon. He asked me to put the URL to his book in an email to him, as he wanted to order the book. He then spent some time looking at the pages and reviews and said he would be ordering the book.

Then Tom asked me if I could call Allen over and I said yes and made the call. In a few minutes, Allen was here. Tom asked how he was doing with that low an A1c. Allen said he felt great and was even surprised that it was that low, as he had not had any readings below 65 mg/dl. Yes, he had many readings in the 70's to low 90's and about the same in less than 105 as in the upper 60's. Allen admitted he would prefer an A1c in the range of 4.9 to 5.5%. He said this caused him to need to find another doctor, as his current doctor would not believe him even though he had the meter readings to prove it. Allen said the doctor told him that he was no longer a patient and was concerned about unreported hypoglycemia. Allen said this is now the second doctor that does not believe he only has one meter and has unreported hypoglycemia on a second meter.

Tom said he would be ordering Dr. Bernstein's book Diabetes Solutions and Allen asked if he wanted to own it or borrow it. Tom said he wanted to own it and have it available for Beverly if she needed to use it. Allen said that sounds like the right idea.

At that point, Tom asked me to loan him a few books. When we were finished, he had four of my books that he wanted to read. In addition, he had three others set aside for later.

Heart Disease Not Caused by High Cholesterol

Every time research discovers something that finds statins are a useless treatment, out come the people being paid by Big Pharma to put down the research and researchers.

Co-author of the study Dr Malcolm Kendrick, a Scottish intermediate care GP, acknowledged the findings would cause controversy but defended them as “robust” and “thoroughly reviewed”.

“What we found in our detailed systematic review was that older people with high LDL (low-density lipoprotein) levels, the so-called “bad” cholesterol, lived longer and had less heart disease.”

Vascular and endovascular surgery expert Professor Sherif Sultan from the University of Ireland, who also worked on the study, said cholesterol is one of the “most vital” molecules in the body and prevents infection, cancer, muscle pain and other conditions in elderly people.

“Lowering cholesterol with medications for primary cardiovascular prevention in those aged over 60 is a total waste of time and resources, whereas altering your lifestyle is the single most important way to achieve a good quality of life,” he said.

Lead author Dr Uffe Ravnskov, a former associate professor of renal medicine at Lund University in Sweden, said there was “no reason” to lower high-LDL-cholesterol.

But Professor Colin Baigent, an epidemiologist at Oxford University, said the new study had “serious weaknesses and, as a consequence, has reached completely the wrong conclusion”.

Another skeptic, consultant cardiologist Dr Tim Chico, said he would be more convinced by randomized study where some patients have their cholesterol lowered using a drug, such as a stain, while others receive a placebo.

He said: “There have been several studies that tested whether higher cholesterol increases the risk of heart disease by lowering cholesterol in elderly patients and observing whether this reduces their risk of heart disease.”

“These have shown that lowering cholesterol using a drug does reduce the risk of heart disease in the elderly, and I find this more compelling than the data in the current study.”

The British Heart Foundation also questioned the new research, pointing out that the link between high LDL cholesterol levels and death in the elderly is harder to detect because, as people get older, more factors determine overall health.

“There is nothing in the current paper to support the author’s suggestions that the studies they reviewed cast doubt on the idea that LDL Cholesterol is a major cause of heart disease or that guidelines on LDL reduction in the elderly need re-valuating,” a spokesman said.