Type 2 diabetes: For 2 years, the drug duo may remain effective

Type 2 diabetes: For 2 years, the drug duo may remain effective

A research shows that taking a combination of two newer medicines is safe in patients who are no longer reacting to metformin and yields clinical benefits for at least 2 years.

level of glucose

Insulin helps control the blood circulating level of glucose. The body does not produce enough insulin for type 2 diabetes, its cells no longer respond effectively to the hormone, or both.

In the long term, a large variety of serious and potentially life-threatening complications may be caused by elevated blood glucose levels. These involve high blood pressure, harm to organs like the heart and kidneys, damage to the nerves, and blindness.

Type 2 diabetes affects more than 30 million people in the United States, according to the Centers for Disease Control and Prevention ( CDC), and accounts for 90–95 percent of all cases of diabetes.

Type 2 diabetes used to be referred to as adult-onset diabetes because it often affects people over 45 years of age. But in recent decades, rates of type 2 diabetes have risen in the U.S. in adolescents, teens , and young adults.

Changes in the lifestyle can regulate or even reverse the disease. In order to regulate the blood glucose levels of patients, physicians often prescribe medications.

Metformin is the first-line treatment, but in some patients, the drug ‘s effectiveness may decrease over time, requiring alternative treatments.

Drug combination

In patients whose blood glucose levels did not react to metformin, a clinical trial called DURATION-8 studied a combination of two newer drugs, exenatide and dapagliflozin.

The trial lasted 28 weeks initially, but it was later extended to 52 weeks. The findings show that the blend was safe and proved to be more successful than either drug alone.

The drug combination was related to lower blood pressure and body weight, in addition to stabilizing blood glucose levels.

The researchers report in the journal Diabetes Care that after a second extension of the trial, the drug duo remained safe and successful 2 years (104 weeks) after treatment began.

“Most diabetes treatment treatments are short-lived, which is why long-term impact testing is helpful,” says first author Dr. Serge Jabbour, Director of the Endocrinology and Diabetes Center Division at Thomas Jefferson University in Philadelphia , PA.

Exenatide belongs to a class of drugs called glucagon-like peptide-1 receptor agonists, which function by stimulating the secretion of insulin, reducing the liver’s release of glucose, and increasing the sense of fullness after a meal.

Dapagliflozin belongs to a class called cotransporter-2 sodium-glucose inhibitors, which increase the amount of glucose excreted in the urine.

“These two groups function synergistically to help regulate the glucose levels of a type 2 diabetes patient and other diabetes-associated interventions,” Dr. Jabbour says. “We can now be more secure about the long-term prescription of these medicines.”

The research was funded by AstraZeneca, which manufactures branded versions of both drugs. The organization also played a role in planning the analysis, collecting the data , and analyzing it.

Study design

The researchers randomly allocated three treatment groups to 695 adults with type 2 diabetes whose blood glucose was not adequately regulated by metformin:

  • A frequent exenatide injection and a normal dose of dapagliflozin by mouth
  • Exenatide and occasional oral placebo on a weekly basis
  • Weekly placebo injection and daily dapagliflozin oral injection

After 2 years, 431 patients remained in the trial. Much of the respondents who dropped out did so because they didn’t want to sign up for a trial extension.

Those who obtained both drugs saw the greatest average reduction in their glycated hemoglobin (HbA1c) levels, an indicator of the stability of blood glucose levels, after adjustments for other potential contributing factors, relative to the beginning of the trial.

There have also been increases in blood glucose levels after fasting and 2 hours after eating in patients who have taken both medications, and decreases in body weight and systolic blood pressure.

The researchers report that the combination of exenatide and dapagliflozin has been tolerated well by patients.

Although patients did not experience any episodes of severe hypoglycemia (dangerously low blood glucose levels), there were more episodes of mild hypoglycemia relative to the other two experimental groups of patients taking both medications.


The authors conclude that for 2 years, with “no unexpected safety results,” the clinical benefits of taking both drugs were sustained. They continue:

“Further studies are needed to investigate whether the combination treatment effects observed in DURATION-8 could potentially extend to a reduced incidence of [cardiovascular] and renal events in patients with type 2 diabetes.”

The authors agree that the relatively high percentage of patients who withdrew from the study after 1 year limits the “robustness” after 2 years of their results.

They remember, finally, that their results do not apply to all patients. Care should be personalized to patients and altered according to how well they are doing.