By Anna E. Mazzucco, Ph.D., Miara Jeffress, 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. Diabetes can even increase your risk of developing cancer. These health problems that are caused by diabetes are more dangerous than the diabetes itself.
Diabetes is becoming more and more common, and is estimated to affect more than 9% of the U.S. population in 2014.1 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 – in fact, all the newer drugs 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 their recommendations by relaxing blood sugar level goals for older adults.
New Warnings about Drugs Containing Saxagliptin and Alogliptin
In April 2016, the FDA issued a warning that five Type 2 diabetes drugs may increase the risk of heart failure. They include:
- Onglyza (saxagliptin)
- Kombiglyze (saxagliptin and metformin extended release)
- Nesina (alogliptin)
- Kazano (alogliptin and metformin)
- Oseni (alogliptin and pioglitazone)
Two studies of more than 20,000 patients reported that patients on drugs containing saxagliptin and alogliptin were more likely to be hospitalized for heart failure than patients taking other diabetes drugs. This was especially the case for patients who already have heart or kidney disease. Although both drugs had the same dangers, saxagliptin was the riskier of the two.2
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. While Farxiga 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, it 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. And meanwhile, the TV commercials for Farxiga make it seem like a miracle drug, not like a drug with potentially deadly side effects.
New Warnings about Januvia, Onglyza, Trajenta, Nesina and Similar Diabetes Drugs
In August 2015, the Food and Drug Administration (FDA) issued a warning that 11 relatively new diabetes drugs may cause severe and disabling joint pain.3 They are listed here:
- Januvia (sitagliptin)
- Onglyza (saxagliptin)
- Trajenta (linagliptin)
- Nesina (alogliptin)
- Janumet XR
- Kombiglyze XR
In addition, a study of more than 16,000 patients reported that patients taking Onglyza were 27% more likely to be hospitalized for heart failure than other diabetes patients.4 The FDA is expected to warn patients about this risk in the near future, but has not yet done so.5
Warnings about Older Diabetes Drugs (Avandia, Actos, and Others)
Avandia (also called rosiglitazone), Actos (pioglitazone), and other similar diabetes drugs have a “black box” warning explaining that these drugs can cause or increase the chances of developing heart failure. The similar drugs include Avandaryl, Avandamet, and Duetact, all of which include either Avandia or Actos as key ingredients.
What can a patient with diabetes do to make sure their medication is actually helping rather than hurting them? The remainder of this article has more detailed information that can help you have a good conversation with your doctor about your diabetes medication.
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.6,7
Avandia was approved by the FDA in 1999, despite concerns about the safety of the drug. FDA required Avandia’s maker, GlaxoSmithKline, to continue to conduct clinical trials to assess the heart complications. Those studies resulted in black box warnings since 2007, warning patients and doctors that Avandia increases the risk of fatal heart failures. A block box warning is the strongest warning the FDA requires, similar to the black box warning about health risks on cigarette packages.
In 2007 and 2010, two research studies were published in the New England Journal of Medicine and the Journal of the American Medical Association, and they concluded that patients taking Avandia were more likely to die than patients taking other diabetes medication.6,7 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.
In 2013, GlaxoSmithKline paid a $229 million settlement to patients harmed by Avandia.8 However 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 some of the label warnings and other restrictions. The FDA did not conclude that Avandia is safe, only that it can cause the same health problems, including congestive heart failure, as other diabetes medications. Nevertheless, the FDA told GlaxoSmithKline that they no longer need to conduct a previously required study comparing Avandia to Actos and other diabetes drugs.
This leaves physicians and patients with limited information about which diabetes drugs are safer, and for which patients. The lawsuits against Avandia have continued and the safety questions still concern many physicians and patients.
The FDA recently came out with its “Watch List” – a list of ten drugs that have adverse effects. Among the ten is the popular diabetes medication, Diabeta. If you are currently taking this medication please be aware there have been reports of skin reactions as side effects. In response, the FDA expanded its section on Adverse Reactions on the label to include: bullous reactions, erythema multiforme, and exfoliative dermatitis.
Do Patients Taking Diabetes Medication Have More 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.9 They are less likely to have hyperglycemia (blood sugar that is too high), 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.10 In fact, in recent years there were 40% more hospital admissions for hypoglycemia than hyperglycemia.
Are these patients overmedicated, resulting in blood sugar that is dangerously low? A 2014 study showed that 23% of diabetes patients hospitalized with low blood sugar died compared to 18% of diabetes patients hospitalized with high blood sugar.7 This suggests that the blood sugar goals recommended by the American Diabetes Association may be too low, especially for older adults. 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.11,12 These 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 found that older diabetes patients with a history of hypoglycemia are more likely to develop dementia.13
In addition to concern about “overtreatment” of diabetes, we should make sure patients get the safest treatment. Unfortunately, that is hard to predict because there have not been studies comparing patients taking all the different treatments.
The Big Picture in Diabetes Medication: What Level of Blood Sugar is Best?
Are people with diabetes getting medications that do more harm than good? Would they be better off with fewer medications? The American Geriatric Society and other experts agree that most adults over the age of 65 do not need to control their glucose levels as tightly as experts have previously recommended. Experts now agree that higher blood sugar (A1C) ranges between 7.5 and 9.0% should be considered instead of the previous goal of 7%14. Other experts have suggested that insulin should be completely avoided in those over 80 if 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.15 For some older patients who are taking care of themselves without daily nursing help, a complicated treatment plan involving several drugs may be too difficult to follow correctly.
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.14,15
Talk with your doctor about the blood sugar goal range that is best for you, considering your lifestyle, other health considerations, and preferences. Read this article carefully to educate yourself about the risks of different diabetes medications before you 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 can help treat diabetes, there are also other things you can do to stay healthy. Having regular check-ups with your doctor will help: Get your blood sugar and dental health checked twice a year, and get your cholesterol levels, kidney function, eyes, and foot health checked at least once a year.16 For more information about these 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. Beware of drugs that are advertised for weight loss, in addition to the ones mentioned above. Recently, Contrave, a drug which was approved by the FDA for weight loss, was put on the 2017 “Watch List” for risks of losing consciousness. Sustained and healthy weight loss cannot be achieved by a pill! It is important to thoroughly read the active ingredients in any pill you are taking. For more tips on easy steps to improve overall health, read this article.
- Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States. http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf Accessed August 2015.
- FDA Warns of Heart-Failure Risk With Two Diabetes Drugs. Medscape. April 05, 2016.
- FDA Drug Safety Communication: FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain. http://www.fda.gov/Drugs/DrugSafety/ucm459579.htm. Accessed August 2015.
- Scirica BM, et al. Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus. N Engl J Med. 369(14):1317-1326.
- FDA Says Certain Type 2 Diabetes Drugs Can Cause Serious Joint Pain. August 28, 2015. http://www.wsj.com/articles/fda-says-certain-type-2-diabetes-drugs-can-cause-serious-joint-pain-1440789273. Accessed August 2015.
- Nissen SEand 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.
- Graham DJ et al. Risk of myocardial infarction, stroke, heart failure, and death in elderly medicare patients treated with Rosiglitazone or Pioglitazone. JAMA. 304(4):411-418.
- 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.
- Centers for Disease Control and Prevention. Staying Healthy With Diabetes.http://www.cdc.gov/diabetes/consumer/healthy.htm. Accessed June 4, 2014.
- Lee, S.J. So Much Insulin, So Much Hypoglycemia. JAMA Internal Medicine May 2014 Volume 174, Number 5. 686-688.
- Lipska KJ, Ross JS,Wang Y, et al. National trends in US hospital admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries, 1999 to 2011. JAMAIntern 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.
- 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.
- 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.