The drug combination for type 2 diabetes remains effective after two...

Patients with type 2 diabetes often take metformin as first-line therapy to stabilize their blood sugar. Eventually, some patients stop responding to metformin and need additional treatment. Several years ago, important short-term studies showed that a combination of two drugs controlled diabetes progression better than either drug alone. New research results now show that this active ingredient combination of dapagliflozin and exenatide remains effective without any loss of effectiveness after two years of continuous use.

Many diabetes management therapies are short-lived, so it is useful to test long-term effects. Our study showed that a combination of dapagliflozin and exenatide controlled patients’ glucose for over two years. That is very encouraging. ”

Serge Jabbour, MD, senior author, director of the Department of Endocrinology and Diabetes Center at Thomas Jefferson University

The results of this multicentre, double-blind, randomized, controlled phase 3 study were published in the journal Diabetes treatment.

A total of 695 adults whose type 2 diabetes was not controlled with metformin were randomly divided into three study groups. One group received weekly exenatide injections in addition to metformin. Another group took dapagliflozin pills daily in addition to metformin, and a third group received both drugs together. The study was an extension of the central DURATION-8 study, which meant that patients were given the option to continue the study for longer.

The two drug classes have an additive effect and improve the effects on a number of diabetes indicators. Dapagliflozin belongs to a class of drugs called sodium-glucose cotransporter-2 (SGLT2) inhibitors, which cause excess glucose to be excreted in the urine. Exenatide belongs to a class of drugs called glucagon-like peptide-1 receptor agonists (GLP-1RAs) that improve glucose-dependent insulin secretion, decrease glucose release by the liver, slow down gastric emptying, and increase satiety. Together, the two drugs promote and maintain better glucose control, additive weight loss, and improve blood pressure.

The results confirmed that the group of patients who received both drugs had better glycemic control than those who received only one of the drugs – and showed, for the first time, that the effects were stable over the extended two-year study period. The study also showed clinically relevant reductions in weight and blood pressure, measures that may contribute to type 2 diabetes and general health. The researchers saw no unexpected safety concerns related to the drug combination in the study participants.

Other studies with both drugs have also shown that metabolic markers such as lipid profile also improve.

“These two classes work synergistically to control glucose levels in a patient with type 2 diabetes and other measures associated with diabetes,” says Dr. Jabbour. “We can now feel more confident about prescribing these drugs over the long term.”

This study was funded by AstraZeneca. AstraZeneca was involved in the study design and protocol development, provided logistical support and received the data that was jointly evaluated by the authors and the sponsor. For a full list of potential competing interests, see the following document.