iGlarLixi combination injection reduces HbA1c, body weight

NEW ORLEANS — Adults with poorly controlled type 2 diabetes assigned a combination insulin glargine and lixisenatide injection saw greater glycemic control, modest weight loss and no additional hypoglycemia risk vs. patients assigned insulin glargine alone, according to data presented at the American Diabetes Association Scientific Sessions.

In a randomized, open-label, parallel-group trial, researchers comparing the efficacy and safety of iGlarLixi (Sanofi Aventis), a titratable fixed-ratio combination of Lantus (basal insulin glargine 100 U/mL) and Lyxumia (lixisenatide), a glucagon-like peptide-1 receptor agonist, vs. insulin glargine alone found the drug was well tolerated over 30 weeks, with a low rate of nausea and vomiting reported in patients.

“There’s high interest in looking at the combination of basal insulin with GLP-1 receptor agonists for their complementary effects on fasting glucose and postprandial glucose,” Vanita R. Aroda, MD, director of the MedStar Community Clinical Research Center at the MedStar Health Research Institute, said while presenting her findings, “as well as for the potential mitigating factors to their individual use.”

Vanita R. Aroda

Aroda and colleagues analyzed data from 736 patients with poorly controlled type 2 diabetes on either basal insulin alone or with up to two oral antidiabetic drugs (mean age, 60 years; 53% women; 92% white; mean diabetes duration, 12 years; average basal insulin therapy use, 3 years; mean BMI, 31 kg/m²). Within the cohort, the mean insulin dose prior to randomization was 35 units; 52% were taking metformin; 32% were taking metformin and sulfonylureas. Included patients remained in poor control (HbA1c greater than 7% despite a morning fasting plasma glucose of 140 mg/dL or less) following a 6-week run-in phase where insulin glargine was either introduced or optimized; any oral antidiabetic agents with the exception of metformin were discontinued prior to the start of the trial.

Researchers randomly assigned patients to iGlarLixi (self-injected once daily in the hour before breakfast) or insulin glargine alone for 30 weeks. Researchers assigned patients taking an insulin dose of less than 30 units daily prior to randomization to “pen A,” delivering insulin glargine and lixisenatide at a 2:1 ratio (20 units; 10 mg lixisenatide). Patients on a daily insulin dose of at least 30 units daily prior to randomization were assigned “pen B,” with a 3:1 ratio of insulin glargine and lixisenatide (30 units; 10 mg lixisenatide), Aroda said.

Primary outcome was change in HbA1c from baseline to week 30.

From screening to baseline (after run-in), mean HbA1c for the cohort fell from 8.5% to 8.1% in both groups. Over the treatment period, patients assigned iGlarLixi saw a further decrease in HbA1c to 6.9% vs. 7.5% for those assigned insulin glargine alone (mean treatment difference, .52%; P < .0001); 55% of iGlarLixi patients achieved an HbA1c of 7% or less vs. 30% of insulin glargine patients.

Patients in the iGlarLixi group also experienced a decrease in body weight (–0.7 kg), whereas the insulin glargine group saw a mean increase of 0.7 kg. (mean difference, 1.4 kg; P < .0001). Both groups experienced similar rates of documented hypoglycemia (40% vs. 42%). Treatment was well tolerated; however, patients in the iGlarLixi group reported more adverse gastrointestinal events (10%) vs. those assigned insulin glargine alone (0.5%).

“This improvement in glycemic control likely reflected the combined effect of insulin glargine on fasting glucose and lixisenatide on postprandial glucose control,” Aroda said during her presentation. “This paradigm of basal insulin with GLP-1 receptor agonist therapy appears to be efficacious, well tolerated with complementary physiologic effects.”

An FDA advisory panel voted 12-2 in favor of recommending approval of iGlarLixi in May. – by Regina Schaffer

Reference:

Aroda VR. 238-OR. Presented at: American Diabetes Association Scientific Sessions; June 10-14, 2016; New Orleans.

Disclosure: Aroda reports receiving research support from Amylin, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eisai, GI Dynamics, GlaxoSmithKline, Halozyme, Hanmi, Intarcia, Janssen, Novo Nordisk, Sanofi and Takeda, and receiving consulting

honoraria from Janssen, Novo Nordisk, and Sanofi.