Feasibility of simplification from a basal-bolus insulin regimen to a fixed-ratio formulation of basal insulin plus a glp-1ra or to basal insulin plus an SGLT2 inhibitor: BEYOND, a randomized, pragmatic trial

OBJECTIVE BEYOND trial evaluated the feasibility of either basal insulin plus glucagon-like peptide 1 receptor agonist (GLP-1RA) or basal insulin plus sodium–glucose cotransporter 2 inhibitor (SGLT2i) to replace a full basal-bolus insulin (BBI) regimen in participants with type 2 diabetes and inadequate glycemic control. RESEARCH DESIGN AND METHODS Participants were randomized (1:1:1) to 1) intensification of the BBI regimen (n = 101), 2) fixed ratio of basal insulin plus GLP-1RA (fixed-combo group; n = 102), and 3) combination of basal insulin plus SGLT2i (gliflo-combo group; n = 102). The primary efficacy outcome was change from baseline in HbA1c at 6 months. RESULTS Baseline characteristics were similar among the three groups (mean HbA1c was 8.6% [70 mmol/mol]). At 6 months, patients experienced similar reduction in HbA1c level (0.6 ± 0.8%, 0.6 ± 0.8%, and 0.7 ± 0.9%, mean ± SD, respectively; noninferiority P < 0.001 vs. BBI), and the proportion of patients with HbA1c ≤7.5% was also similar (34%, 28%, and 27%, respectively; P = 0.489). Total insulin dose increased in the BBI group (62 units/day) and decreased both in the fixed-combo and gliflo-combo groups (27 units/ day and 21 units/day, respectively; P < 0.01). The proportion of patients with hypoglycemia was 17.8%, 7.8%, and 5.9%, respectively (P = 0.015). There were 12 dropouts in the fixed-combo group, 9 in the gliflo-combo group, and none in the BBI group. CONCLUSIONS BEYOND provides evidence that it is possible and safe to switch from a BBI regimen to either a once-daily fixed-combo injection or once-daily gliflozin added to basal insulin, with similar glucose control, fewer insulin doses, fewer injections daily, and less hypoglycemia.