Up to 95 percent of people with diabetes have type 2 diabetes, which includes approximately 37 million Americans. Once diagnosed, these individuals have to keep an eye on their blood sugar (or blood glucose). Treatment usually begins with exercise, diet and metformin, an oral drug that decreases the amount of sugar the body absorbs from food and processes in the liver.

Insulin is a hormone that moves the sugar you need for energy from your blood into your cells. Type 2 diabetes occurs when the pancreas is unable to create enough insulin—or resistance occurs from the body’s cells to use insulin. People with diabetes have too much sugar (glucose) in their blood.

When blood sugar is not controlled well enough with exercise, diet and metformin, most people will need another diabetes drug added to their treatment regimen. However, there isn’t a consensus among doctors concerning which drug is the best. A new study from the National Institute of Diabetes and Digestive and Kidney Disease gives doctors and patients more information to use when making this choice.

Searching for the Best Add-On Diabetes Drug

The study is called the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study. Researchers began the GRADE study in 2013 at 36 U.S. sites. It included over 5,000 patients with type 2 diabetes who were already on metformin. The primary goal of the study was to find out which added medication would be best at keeping glycated hemoglobin—also called A1c—at target range of 7 percent. A1c is a measurement of the average blood sugar level over about three months. An A1c of 7 is considered adequate blood sugar control to reduce complications from the disease, such as kidney, eye or nerve damage or cardiovascular disease. The added drugs tested were…

  • Glargine U-100, a long-acting insulin injection
  • Glimepiride (Amaryl), an oral drug that increases release of insulin by the pancreas
  • Liraglutide (Victoza), an injection drug that decreases appetite and increases insulin release
  • Sitagliptin (Januvia), an oral drug that decreases absorption of insulin from the gut

All the participants had been diagnosed with type 2 diabetes for less than 10 years. They were randomly assigned to one of the four drugs. The results of the study after about four years are reported in The New England Journal of Medicine

  • All four drugs improved A1c.
  • Both Glargine and Victoza lowered A1c modestly but significantly more than the other drugs.
  • Treatment effects did not differ based on age, sex, race, or ethnicity.
  • Patients who had the highest A1c at the start of the study had the most benefit from Glargine, Victoza and Amaryl, and the least benefit from Januvia.
  • The side effect of low blood sugar (hypoglycemia) was most common with Amaryl at about two percent of patients. The drug least likely to cause hypoglycemia was Januvia at less than one percent.
  • Gastrointestinal side effects were more common with Victoza.
  • All four drugs increased weight loss, which helps stabilize blood sugar. Victoza and Januvia caused the most weight loss with averages of four to seven pounds.

Newer Drugs in the Mix

Despite the benefit of adding another drug, only about 25 percent of the patients were able to maintain their A1c in the target range during the length of the study. The research team concludes that their findings can help patients and doctors make the best choice for adding another type 2 diabetes drug, but more work needs to be done to find the best way to maintain target A1c over time.

One shortcoming of the study was that it started before a new class of drugs called SGLT2 inhibitors was approved by the U.S. Food and Drug Administration. These drugs lower blood glucose levels by blocking the absorption of sugar from the blood. Further research that includes new drug options will be needed to recommend the best evidence-based drug choices for the treatment of type 2 diabetes.

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