Adding insulin detemir to metformin/liraglutide further lowers HbA1c in type 2 diabetes patients not achieving control with oral therapy

A treatment-intensification sequence starting with liraglutide added to metformin followed by adding basal insulin detemir further improves glycemic control with a low risk of hypoglycemia in patients who don’t reach their hemoglobin (Hb) A_1c target on metformin plus liraglutide, reported Julio Rosenstock, MD.
     No general agreement exists on how to advance treatment when metformin (with or without a sulfonylurea) fails to get patients to target HbA_1c levels. Basal insulin and glucagon-like peptide-1 (GLP-1) receptor agonists are options, but more data are needed to define the optimal sequential order for adding them and the response rates when adding a GLP-1 receptor agonist first.
     “There are no data on starting insulin in GLP-1 receptor agonist-treated insulin-naïve patients with type 2 diabetes,” said Rosenstock, Director of the Dallas Diabetes and Endocrine Center.
     In his 38-week study, 987 patients with suboptimal glycemic control on metformin with or without a sulfonylurea had liraglutide, 1.8 mg, added to their regimen (the run-in phase). In 323 patients whose HbA_1c levels remained above 7.0% at week 12, patients were randomized to either metformin/liraglutide (1.8 mg) or metformin/liraglutide (1.8 mg) with basal insulin detemir added (26-week main treatment phase). The 498 patients who achieved an HbA_1c less than 7.0% on metformin/liraglutide remained in an observational arm continuing on metformin/liraglutide.
     During the run-in phase, 61% of patients reached an HbA_1c less than 7.0%, with a decrease in HbA_1c of 1.3% and a decrease in body weight of 4.4 kg. After the 26-week main period, patients randomized to the addition of insulin detemir to metformin/liraglutide had a further 0.5% reduction in HbA_1c, while HbA_1c remained stable in the metformin/liraglutide group.
     Forty-three percent of patients randomized to triple therapy reached target HbA_1c of less than 7% at 26 weeks versus 17% remaining on metformin/liraglutide.
     Body weight decreased in all groups, mainly during the run-in phase; weight loss was maintained in group that had insulin detemir added to their regimen. The rates of minor hypoglycemia were low in each group (0.2 events per patient per year in the triple therapy group and 0.3 events per patient per year in the observational group), with no major hypoglycemic events during the main treatment period.