SAN DIEGO – When basal insulin alone does not achieve glucose targets in type 2 diabetes, a single fixed-dose injection of insulin degludec and liraglutide (IDegLira) is as effective as multiple insulin injections and has a significantly lower risk of hypoglycemia, according to a randomized, multicenter, open-label, industry-sponsored trial.
After 26 weeks of treatment, average hemoglobin A1c levels dropped similarly with once-daily IDegLira (1.48%) as with basal insulin glargine U100 plus mealtime injections of short-acting insulin aspart (1.46%; P less than .0001 for noninferiority), reported Liana K. Billings, MD, at the annual scientific sessions of the American Diabetes Association.
Dr. Liana K. Billings
Patients also needed significantly less insulin and lost significantly more weight on IDegLira, compared with the basal-bolus regimen. “This is some of the most robust, most impressive data I’ve seen in years,” Julio Rosenstock, MD, director of the Dallas Diabetes and Endocrine Center in Texas, commented from the audience. Dr. Rosenstock was not involved in the trial and has studied other combination regimens for type 2 diabetes.
The advent of new insulins and adjunct therapies gives clinicians many potential algorithms for treating type 2 diabetes patients. The ADA recommends that health care professionals consider dual or triple therapy if patients do not meet glycemic targets with lifestyle changes and metformin alone. However, weight gain, hypoglycemia, and complex treatment regimens can make it difficult to intensify treatment in the real world, Dr. Billings said.
Insulin degludec is an ultra–long-acting basal insulin analogue, while liraglutide is a GLP-1 receptor agonist. The open-label, phase III DUAL VII study compared once-daily IDegLira injection (Xultophy, Novo Nordisk) with once-daily basal insulin glargine (Lantus, Sanofi) U100 plus bolus insulin aspart (NovoLog, Novo Nordisk) at mealtimes in 506 adults with type 2 diabetes. All patients were on metformin and glargine (typically 34 U) at baseline. Most were in their late 50s and obese, with an average 13-year duration of type 2 diabetes and HbA1c levels of 8.2% despite treatment. The IDegLira group started at 16 U and titrated by 2 U twice weekly to reach a fasting glucose target of 72-90 mg/dL. Basal-bolus patients maintained their baseline glargine dose and added 4 U mealtime bolus insulin aspart, titrating to target by 1 U twice weekly. The primary endpoint was change in HbA1c levels after 26 weeks. More than 98% of patients completed the trial. Approximately two-thirds of patients in both arms achieved an HbA1c level below 7%, but IDegLira recipients were significantly more likely to do so without gaining weight or experiencing hypoglycemia during the last 12 weeks of treatment (odds ratio, 10.39; 95% CI, 5.76-18.75). The IDegLira arm received significantly less daily insulin than the basal-bolus arm (40 U versus 84 U; P less than .0001), and IDegLira patients lost an average of 0.93 kg, while the comparison group gained 2.64 kg. Rates of serious adverse events were low and similar between arms. The cumulative rate of nausea was higher with IDegLira (11.1%) than with basal-bolus therapy (1.6%), Dr. Billings said. There were no deaths or unexpected adverse events.
Novo Nordisk makes Xultophy and funded the trial. Dr. Billings reported having served on advisory panels and speaker bureaus for Novo Nordisk.