Safety, Efficacy of Degludec/Liraglutide Fixed-Ratio Combination in Uncontrolled T2D
Only trial thus far that compared a fixed-ratio combination of basal insulin and glucagon-like peptide-1 receptor agonist with basal-bolus.
In patients with uncontrolled type 2 diabetes receiving basal insulin and metformin, treatment with insulin degludec/liraglutide fixed-ratio combination (IDegLira) may reduce glycated hemoglobin (HbA1c) levels comparable to those of basal-bolus insulin with lower hypoglycemia rates and weight loss vs weight gain, according to a phase 3b, multinational, open-label study published in Diabetes Care.
In the first trial to compare the efficacy and safety of a fixed-ratio combination of basal insulin and a glucagon-like peptide-1 receptor agonist (GLP-1RA) with basal-bolus insulin, researchers randomly assigned 506 patients with uncontrolled type 2 diabetes receiving insulin glargine 20 to 50 units/day and metformin to receive either IDegLira or insulin glargine and insulin aspart 4 or fewer times a day.
After 26 weeks of treatment, HbA1c decreased from 8.2% (66 mmol/mol) to 6.7% (50 mmol/mol) in patients taking IDegLira and from 8.2% (67 mmol/mol) to 6.7% (50 mmol/mol) in patients taking basal-bolus insulin, confirming IDegLira noninferiority vs basal-bolus insulin (P <.0001). In addition, 66% of patients taking IDegLira compared with 67% of patients taking basal-bolus insulin achieved an HbA1c <7.0% (53 mmol/mol).
Fasting plasma glucose reductions were similar between the groups, but lunch, dinner, and bedtime self-monitored plasma glucose measurements were significantly lower for patients taking basal-bolus insulin.
The total daily insulin dose was found to be lower in the IDegLira group (40 units) than in the basal-bolus insulin group (84 units total; 52 units basal), as well as the incidence of severe or blood glucose-confirmed symptomatic hypoglycemia events. In addition, body weight decreased for patients in the IDegLira group and increased for patients in the basal-bolus insulin group.
The authors concluded that "compared with basal-bolus, IDegLira offers an alternative well-tolerated treatment with fewer injections, doses taken independently of meals, lower total daily insulin dose, reduced monitoring, weight loss, and reduced rate of hypoglycemic episodes."
Billings LK, Doshi A, Gouet D, et al. Efficacy and safety of IDegLira versus basal-bolus insulin therapy in patients with type 2 diabetes uncontrolled on metformin and basal insulin; DUAL VII randomized clinical trial [published online February 26, 2018]. Diabetes Care. doi: 10.2337/dc17-1114