There is consensus that metformin is the best drug for treating Type 2 diabetes. As I wrote recently, it does not cause blood sugar to fall below normal, it often produces weight loss, and it’s inexpensive. Debate rages on over the role of other drugs that are typically added once metformin alone is not enough to bring high blood sugar levels back towards normal. All of the available alternatives have some problems, both the older, inexpensive drugs and the newer, very costly medications.
I realize the medication guide below is a lot to digest. But I also know that patients, and their families, are hungry for reliable, accessible information about their alternatives. So please, proceed.
Sulfonylureas are an older group of drugs, with generic glipizide, which was approved by the Food and Drug Administration in 1984, the leading medication. It costs pharmacies only $0.07 per day. These drugs work by increasing the amount of insulin produced by the pancreas. Lowering blood sugar too much can be a side effect, so skipping meals can cause big problems. Of all patients in the U.S. with diabetes, 17 percent take a sulfonylurea.
DPP inhibitors (short for dipeptidyl peptidase) are newer, very expensive medications ($14 per day for sitagliptin, brand name Januvia, approved in 2006). It works by interfering with the body’s hormone glucagon that would normally keep blood sugar levels higher. These drugs can cause low blood sugar (though not as much as glipizide) and may increase the risk of heart problems. Nearly a quarter of all diabetes patients in the U.S. take DPPs.
Glitazones are a middle-aged group of drugs that work by reducing insulin resistance in the body. Past concerns about heart disease and cancer risks have reduced their use from their peak popularity in the 1990s. Only 5 percent of all patients with diabetes take a glitazone. After reviewing the most recent data, I’ve started prescribing these drugs again and believe that they are underused. The leading drug is pioglitazone, which was approved in 1999 and costs pharmacies $0.15 for a single day's dose.
Incretins are injected medications that reduce blood sugar through several mechanisms. They are chemically related to the venom of both the Gila monster and the platypus. Now that they are available for weekly injection (rather than once or more per day), they can be quite effective in diabetes treatment and are used by 6 percent of patients with diabetes. These injections are very expensive, however. Extended release exenatide (brand name Bydureon) was approved in 2012 and costs pharmacies $158 per week ($22 per day).
SGLT inhibitors (short for sodium-glucose co-transporter) are the latest diabetes drug class. These drugs work by making the kidneys dump extra blood sugar into the urine, which then passes out of the body. Of course, microbes can thrive in sugary urine. So far this year, I’ve already seen a patient with a severe vaginal yeast infection and a bacterial bladder infection. About 10 percent of people with diabetes in the U.S. now take an SGLT inhibitor. The leading drug is canagliflozin (brand name Invokana), which was approved in 2013 and costs pharmacies $15 per day of treatment.
There is no obvious diabetes drug to add once metformin alone is insufficient, an eventual necessity in almost all patients. My own practices tend towards the older, inexpensive sulfonylureas and glitazones. I believe that the recognized problems of these tried and true drugs may be slightly better than the newer drugs, where the full range of side effects is not yet known.
Yet, even these medications are often not enough. In the next post, I'll explain the many available forms of injectable insulin.
Randall Stafford, MD, PhD, a professor of medicine and director of the Program on Prevention Outcomes and Practices, practices primary care internal medicine at Stanford. He is developing practical strategies to improve how physicians and consumers approach chronic disease treatment and prevention.
This is the sixth piece in a series, “Breaking Down Diabetes,” created for those with or at risk for diabetes as well as their family and friends. Previous blog posts addressed the pre-diabetes, diabetes complications, and goals for diabetes management beyond blood sugar. Some data for this report come from IQVIA, Inc., previously known as QuintilesIMS. For additional information, please contact firstname.lastname@example.org.