Insulin/liraglutide combination effective in uncontrolled diabetes, study finds

Combination insulin degludec and liraglutide appears to be as effective as up-titration of glargine at reducing HbA1c in patients with uncontrolled type 2 diabetes, according to a new study.

The DUAL V randomized clinical trial assessed the relative efficacy and safety of unlimited titration of a once-daily injection of glargine versus a once-daily fixed-ratio injection of degludec (dose limit, 50 U)/liraglutide (dose limit, 1.8 mg). Results were published online on March 1 by the Journal of the American Medical Association. The study was a phase III noninferiority trial of a drug combination not yet approved by the FDA and was funded by Novo Nordisk.

The trial enrolled adult patients with type 2 diabetes and an HbA1c level of 7% to 10% who were taking stable doses of glargine and metformin. Of the 557 patients randomized (mean age, 58.8 years; 49.7% women), 92.5% completed the 26-week trial. Researchers included 278 patients taking degludec/liraglutide and 279 patients who stayed on glargine in their primary analysis.

The primary end point was change in HbA1c from baseline to 26 weeks. At 26 weeks, mean HbA1c level decreased by 1.81% for the degludec/liraglutide group (SD, 1.08%) and by 1.13% for the glargine group (SD, 0.98%), an estimated treatment difference (ETD) of −0.59% (95% CI, −0.74% to −0.45%). This result demonstrated noninferiority of degludec/liraglutide compared with glargine (1-sided P<0.001).

Secondary end points were change from baseline in body weight and number of treatment-emergent hypoglycemic episodes during 26 weeks. Degludec/liraglutide was associated with weight loss of −1.4 kg, compared to weight gain of 1.8 kg for glargine, an ETD of −3.2 kg (P<0.001). Degludec/liraglutide was also associated with fewer confirmed hypoglycemic episodes (episodes/patient-year exposure, 2.23 for degludec/liraglutide vs. 5.05 for glargine; P<0.001). Both groups had similar rates of adverse events, although more non-serious gastrointestinal adverse events were reported with degludec/liraglutide (79 vs. 18 for glargine).

“As a once daily, single injection that is effective, associated with weight loss, and a low risk of hypoglycemia, degludec/liraglutide may overcome many of the barriers to treatment intensification in patients treated with basal insulin,” the study authors wrote. They noted limitations to their study, such as how its open-label nature may have biased reporting of adverse events and how its clinical applicability is limited to those who fit the inclusion and exclusion criteria.

A separate study, published online on Feb. 24 by The Journal of Clinical Endocrinology & Metabolism, looked at the mechanisms of action of liraglutide in obese patients with type 2 diabetes being treated with high-dose insulin. In this randomized, double blind, placebo-controlled trial, researchers found that adding liraglutide to high-dose insulin therapy controls glycemia primarily through improving insulin secretion, not through suppression of glucagon secretion. They did not find significant changes in insulin sensitivity. Compared to the placebo group, the liraglutide group had decreases in liver fat and subcutaneous fat decreased but visceral fat did not change.