EASD: Intensified Treatment with Basal Insulin Improves Control and Weight Loss

Additionally, intensifying treatment carried a low risk for hypoglycemia. Researchers conducted a 64-week trial consisting of a 12-week run-in followed by a 26-week randomized trial and a 26-week extension. The study was designed to compare the safety and efficacy of metformin plus Liraglutide 1.8 mg plus insulin detemir vs. metformin and liraglutide 1.8 mg alone.

Researchers enrolled 988 patients, 821 of whom completed the 12-week run-in. Following this, patients with HbA1c <7% were assigned to an observational arm and continued treatment with metformin and liraglutide for 52 weeks. Those with HbA1c ≥7% were randomly assigned to metformin and liraglutide or metformin and liraglutide plus titrated insulin detemir (from 10 U/day) for 52 weeks. Intensification with insulin detemir was available 26 and 38 weeks post-randomization to those patients with HbA1c ≥8% assigned to metformin and liraglutide alone. During this time, 24 such patients intensified with insulin detemir.

Sixty-one percent of patients who completed the run-in reached a target HbA1c <7% and entered the metformin plus liraglutide arm; the remaining patients were randomized, according to the study abstract. The mean HbA1c among patients who were randomized was 8.3%; this decreased to 7.6% after run-in.

At 52 weeks post-randomization, HbA1c decreased by 0.5% in the intensification arm compared with an increase of 0.01% in the metformin plus liraglutide arm (estimated treatment difference: -0.51%; 95% CI, -0.70 to -0.31). At this time 52% patients in the intensification arm reached HbA1c <7% vs. 22% of those in the metformin and liraglutide arm (randomized patients; OR=3.94; 95% CI, 2.37-6.55).

Weight loss occurred among all groups, at a mean -3.5 kg to -4.3 kg during run-in. Weight remained stable with no increases between randomization and week 52 (-0.05 kg with intensification) and decreased further with metformin and liraglutide (randomized patients; -1.02 kg; estimated treatment difference: 0.97; 95% CI, 0.04-1.91).

Minor hypoglycemia occurred at a rate of 0.12 events per subject-year for metformin plus liraglutide (observational), 0.03 events per subject-year (randomized) and 0.23 events per subject-year for intensification. Between randomization and 52 weeks, there were no major hypoglycemic events among groups.

Bain SC. Abstract #73. Presented at: The European Association for the Study of Diabetes 47th Annual Meeting; Sept. 12-16, 2011; Lisbon