Glycemic and non-glycemic benefits of initial triple therapy versus sequential add-on therapy in patients with new-onset diabetes: results from the EDICT study.

Introduction: To compare carotid intima-media thickness (cIMT) and liver fat content in subjects who maintained good glycemic control for 6 years on initial triple therapy with metformin/exenatide/pioglitazone versus sequential add-on therapy with metformin followed with glipizide and basal insulin in subjects with new-onset diabetes.

Research design and methods: Liver fat content and cIMT were compared among patients with T2DM who received initial triple therapy with metformin/pioglitazone/exenatide (n=29) versus metformin, followed by stepwise addition of glipizide and then insulin glargine (n=26) and who maintained HbA1c<6.5% for 6 years in Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes.

Results: After 6 years in subjects receiving initial triple therapy with metformin/pioglitazone/exenatide and subjects receiving sequential addition of metformin followed by glipizide and insulin glargine had a mean HbA1c of 5.7% vs 6.0%, respectively, p=NS. Nonetheless, subjects receiving sequential add-on therapy experienced a greater increase in cIMT and manifested greater liver fat content and fibrosis than subjects receiving initial triple therapy.

Conclusions: Including pioglitazone plus exenatide in the glucose-lowering regimen slows the progression of cIMT and was associated with lower hepatic fat content and fibrosis compared with subjects receiving sequential add-on therapy without pioglitazone and exenatide despite comparable optimal glycemic control.

Trial registration number: NCT01107717.