By Anna E. Mazzucco, Ph.D. and Diana M. Zuckerman, Ph.D.
Nearly 20 million Americans have type 2 diabetes, also known as adult-onset diabetes, a condition where a person’s body does not respond well to sugar or store it properly. Diabetes can cause many very serious health problems, including kidney disease, blindness, amputation and, most notably, heart disease. These complications caused by the disease, not the diabetes itself, are usually what cause serious long-term effects or death.
Diabetes is becoming more and more common, doubling from 1995 to more than 9% in 2012.1,2 This increase, and the fact that people often take diabetes medication for many years, has meant that a diabetes drug can make a lot of money for a pharmaceutical company. As a result, many drugs to treat diabetes have come on the market in the last several years. But unfortunately, it’s not clear if the new drugs are better than the old ones. Several newer diabetes drugs, such as Avandia and Farxiga, both have serious safety concerns (see below for more details).
There is also uncertainty about the best way to treat diabetes, especially among older adults. Recent studies suggest that using drugs to keep blood sugar very tightly controlled in type 2 diabetes patients, especially older adults, may not always be beneficial. If blood sugar gets too low, this can cause serious health problems in older adults. And the benefits of tight blood sugar control are likely to only help younger people. In other words, older adults may be less likely to benefit, and more likely to be harmed, by the traditional guidelines for blood sugar (glucose). Medical experts are now starting to change theirrecommendations by relaxing blood sugar level goals for older adults.
Concerns about Avandia, Actos, Farxiga, and other Diabetes Drugs
Patients taking diabetes drugs should be aware that Avandia (also called rosiglitazone), Actos (pioglitazone), and other similar diabetes drugs have a “black box” warning explaining that these drugs can cause or increase heart failure. Other, similar drugs include Avandaryl (combination of rosiglitazone and glimepiride), Avandamet (rosiglitazone and metformin), and Duetact (pioglitazone and glimepride).
In January 2014, the FDA approved a new diabetes drug, Farxiga. Although this drug is less likely to cause heart disease, it has other serious side effects, which may include bladder cancer and breast cancer.
More information about how a medication intended to improve the health of diabetics could actually increase their risks are described below. If you take any of these medications, or are considering them, we suggest you talk with your doctor about which choice is best for you based on the risks, benefits, and your particular treatment goals.
Diabetes Medication Resulting in ER Visits?
A 2014 report from the Centers for Disease Control and Prevention (CDC) showed that type 2 diabetes patients are having fewer of some types of health problems than they used to.3 They are less likely to have hyperglycemia (too high blood sugar), stroke, or heart attack (they each went down almost 70% between 1995 and 2010). Unfortunately, another report found that more type 2 diabetes patients are going to the ER for hypoglycemia (low blood sugar) than before.4 From 1999 to 2011, the rate of hospital admissions for hypoglycemia went up 12% among U.S. Medicare beneficiaries. In fact, over this time period there were 40% more hospital admissions for hypoglycemia than hyperglycemia.
Experts wondered if these patients were overmedicated, resulting in blood sugar that was lower than was safe for them. For example, a 2014 study showed that diabetes patients hospitalized with low blood sugar had a higher death rate than those hospitalized with high blood sugar (23% versus 18%).4 Therefore, they suggest that the blood sugar goals recommended by the American Diabetes Association may be too low, especially for older adults. Because the American Diabetes Association blood sugar goals have been set to a specific number rather than a range, some experts worry that doctors and patients have focused only on lowering blood sugar, and not on the potential risks of getting it too low. Specifically, the previous recommendations suggested keeping a blood sugar level (i.e. “A1C level” –which measures sugar on red blood cells) to less than 7%. Older adults may have to carefully coordinate insulin, several other medications, and meals to keep their blood sugar “just right”, and may physically be more likely to suffer health problems when blood sugar gets too low.
In fact, two 2014 studies have shown that diabetes patients above the age of 75 or 80 are more likely to have low blood sugar (hypoglycemia) than younger diabetes patients.4,5 These studies also showed that older diabetes patients were more likely than younger patients to be hospitalized and suffer other complications of hypoglycemia such as shock, seizures, falls and loss of consciousness. Another study also found that older diabetes patients with a history of hypoglycemia are more likely to develop dementia than older diabetes patients who haven’t had hypoglycemia, although the reason for that isn’t clear.6 One study which looked at hospitalizations due to hypoglycemia between 2007 and 2011 estimated a cost of more than $600 million dollars.
In addition to concern about “overtreatment” of diabetes, we should make sure patients get the most effective treatment. Safety concerns about several diabetes medications have been in the news and caused controversy over actions by the U.S. Food and Drug Administration (FDA).
Avandia and Actos Concerns
Avandia was a very popular drug for diabetes for many years, but is it safe? There is research evidence that patients taking Avandia are more likely to die compared to diabetic patients taking other drugs. The FDA defends the use of Avandia, but the drug remains controversial.
Avandia was approved by the U.S. Food and Drug Administration (FDA) in 1999 despite concerns from FDA scientists and other experts about the safety of the drug. As a condition of FDA approval, Avandia’s maker, GlaxoSmithKline, was required to continue to conduct clinical trials to assess the seriousness of heart complications related to the drug’s use.
Since 2007, the FDA has required Avandia to include a black box warning for patients and doctors that it increases the risk of heart failure, which can be fatal. A block box around a warning about risks is the strongest warning the FDA requires, similar to the black box warning about health risks on cigarette packages. This black box warning was required after a meta-analysis by Dr. Steven Nissen and Kathy Wolski, MPH, combining data from 42 small studies, indicated that Avandia increases the risk of heart attack by 40%, compared to placebo.7 However, the data from the studies analyzed were short-term (six months or less) and the studies differed widely, so that combining them in a meta-analysis was questionable.
However, in June, 2010, the Journal of the American Medical Association published two research studies that concluded that patients taking Avandia were more likely to die than patients taking other diabetes medication. One, a meta-analysis of 56 studies of more than 35,000 patients, was also written by Nissen and Wolski. The other is a 3-year comparison of Avandia and Actos, based on more than 220,000 patients and analyzed by FDA scientist Dr. David Graham and his colleagues.
After Dr. Nissen presented his findings to an FDA Advisory Committee in July, 2010, the Committee expressed strong concerns about the safety of Avandia. This was followed by media coverage accusing GlaxoSmithKline of covering up their own data showing increased risks of heart disease. In September, 2010, the FDA began requiring special certification for healthcare providers who prescribed Avandia. Only specially certified pharmacies could dispense it, and only patients who were already taking it before the restrictions or new patients who could not use any other glucose-lowering medications were eligible to take it. As a result, Avandia prescriptions plunged.
While law suits continue, in 2013 GlaxoSmithKline paid a $229 million settlement over Avandia.8 However, GlaxoSmithKline continued to argue the merits of Avandia, especially compared to other diabetes drugs. The FDA held an Advisory Committee meeting in June 2013 , and this time, Dr. Nissen was not invited as a speaker, and, persuaded by the presentation from GSK, the Committee recommended lifting many of the restrictions on Avandia.. In November 2013, the FDA announced its conclusion that Avandia does not pose a greater risk of heart disease than the most commonly used Type 2 diabetes drugs and withdrew the stronger label warnings and other restrictions. It is important to emphasize that the FDA did not conclude that Avandia is safe, but only that it can cause the same health problems as other diabetes medications. Rather than continuing to gather data on these widely used drugs, the FDA told GlaxoSmithKline that they no longer need to conduct a previously required study comparing Avandia to Actos and other diabetes drugs.
The FDA’s decision to no longer require a comparison study of popular diabetes drugs leaves physicians and patients with limited information about which diabetes drugs are safer, and for which patients. As a result of media attention and the black box warning, many doctors and patients have decided that the risks are too high. Prescriptions for Avandia remain low, but questions remain about the safety of other diabetes drugs, some of which had not been scrutinized as carefully as Avandia. The law suits against Avandia have continued and the safety questions still concern many physicians and patients.
A New Drug with Concerns: Farxiga
In January 2014, the FDA approved a new diabetes drug, Farxiga, which the FDA hoped would be safer than Avandia, Actos, and other drugs because it works differently. Unfortunately, Farxiga seems to be less effective than Avandia, Actos, and several other diabetes drugs. And, while it may have less risk for heart disease, it increases the risk of genital fungal infections and bladder infections, kidney problems, and may increase the risk of bladder cancer and breast cancer. If you are considering this medication, keep these risks in mind and understand that it often takes a few years after a drug is widely sold for researchers to determine exactly what the risks are.
Meanwhile, if you or anyone in your family has had cancer, especially breast or bladder cancer, be sure to mention this to your doctor before considering Farxiga, because that could make Farxiga more dangerous for you. For more information, see our article on Farxiga. The FDA has asked the maker of Farxiga to do more studies looking at bladder cancer and other risks potentially associated with the drug, but for now these questions remain.
Changing Blood Sugar Recommendations
A major question is whether people with diabetes are getting medications that do more harm than good, and whether they would be better off with fewer medications. The Choosing Wisely Campaign (a joint effort of Consumer Reports and medical experts) and the American Geriatric Society agree that most adults over the age of 65 do not need to control their glucose levels as tightly as experts have previously recommended. The risks of a target blood sugar level (A1C) of less than 7% (such as low blood sugar and resulting complications) may be greater than the likely benefits for older patients, and therefore experts agree that higher blood sugar (A1C) ranges between 7.5 and 9.0% should be considered instead, depending on patient factors and preferences.9 Other experts have suggested that insulin use should be completely avoided in those over 80 as much as possible.10
For example, a recent study found that use of the wrong insulin product (e.g. long-acting versus rapid-acting) and reduced food intake were two of the reasons that patients ended up going to the hospital with low blood sugar.5 For some older patients who are taking care of themselves without daily nursing help, a complicated treatment plan involving multiple drugs may not be the best choice.
As a result of these new findings regarding low blood sugar, in 2013, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes released updated recommendations calling for a more individualized approach to treatment, considering each patient’s health, preferences, support system (including meal planning abilities), risk of low blood sugar, cost, and other factors.11,12
Talk with your doctor about the blood sugar goal range that is best for you, considering your lifestyle, other health considerations, and preferences. When choosing diabetes medication, talk with your doctor about the risks and benefits of each choice and how they might affect you. Consider the medical histories of your parents and siblings, since that can influence your health risks as well. Ask questions until you feel confident that you understand all the possible options.
While medication is often an important part of treating diabetes, there are also other things you can do to stay healthy. Having regular check-ups with your doctor are important for making sure that your treatment plan is working for you. The Centers for Disease Control and Prevention (CDC) recommends that people with diabetes get their blood sugar and dental health checked twice a year, and also get their cholesterol levels, kidney function, eyes and foot health checked at least once a year.13 For more information about their recommendations, see this article. And for recommendations about the risks and benefits of common medical procedures for adults over 65, click here.
Most important, all patients benefit from a balanced diet, regular exercise and healthy weight. For more tips on easy steps to improve overall health, read this article.
- Centers for Disease Control and Prevention. Increasing Prevalence of Diagnosed Diabetes — United States and Puerto Rico, 1995–2010. 2012. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6145a4.htm. Accessed June 2014. ▲
- Centers for Disease Control and Prevention. National Diabetes Statistics Report. 2014. http://www.cdc.gov/diabetes/pubs/statsreport14.htm?loc=americandiabetesassociation. Accessed June 2014. ▲
- Gregg EW, Li Y,Wang J, et al. Changes in diabetes-related complications in the United States, 1990-2010. N Engl J Med. 2014;370(16):1514-1523. ▲
- Lipska KJ, Ross JS,Wang Y, et al. National trends in US hospital admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries, 1999 to 2011. JAMA Intern Med. 2014 ▲
- Geller, A.I. et al. National Estimates of Insulin-Related Hypoglycemia and Errors Leading to Emergency Department Visits and Hospitalizations. JAMA Intern Med. 2014;174(5):678-686. ▲
- Whitmer, R.A. et al. Hypoglycemic Episodes and Risk of Dementia in Older Patients with Type 2 Diabetes Mellitus. JAMA. 2009 April 15; 301(15): 1565–1572. ▲
- Nissen SE and Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007 Jun 14;356(24):2457-71. ▲
- Reuters. Glaxo to pay $229 million to settle Avandia suits with 8 states. July 2013. http://www.reuters.com/article/2013/07/24/glaxosmithkline-avandia-idUSL1N0FU2G220130724. Accessed June 2014. ▲
- American Geriatrics Society. 5 Things Physicians and Patients Should Question. http://www.americangeriatrics.org/files/documents/Five_Things_Physicians_and_Patients_Should_Question.pdf. Accessed June 4, 2014. ▲
- Lee, S.J. So Much Insulin, So Much Hypoglycemia. JAMA Internal Medicine May 2014 Volume 174, Number 5. 686-688. ▲
- American Diabetes Association. Standards of Medical Care in Diabetes- 2013. Diabetes Care, 36 (1), S11- S66. 2013. ▲
- Inzucchi, S.E. et al. Management of Hyperglycemia in Type2 Diabetes: A Patient-Centered Approach. Diabetes Care, 35, 1364- 1379. 2012. ▲
- Centers for Disease Control and Prevention. Staying Healthy With Diabetes. http://www.cdc.gov/diabetes/consumer/healthy.htm. Accessed June 4, 2014. ▲