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

Dario Giugliano, Miriam Longo, Paola Caruso, Rosa Di Fraia, Lorenzo Scappaticcio, Maurizio Gicchino, Michela Petrizzo, Giuseppe Bellastella, Maria Ida Maiorino, Katherine Esposito, Dario Giugliano, Miriam Longo, Paola Caruso, Rosa Di Fraia, Lorenzo Scappaticcio, Maurizio Gicchino, Michela Petrizzo, Giuseppe Bellastella, Maria Ida Maiorino, Katherine Esposito

Abstract

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.

Trial registration: ClinicalTrials.gov NCT04196231.

© 2021 by the American Diabetes Association.

Figures

Figure 1
Figure 1
Proportion of patients achieving HbA1c ≤7.0% (top), ≤7.5% (middle), or ≤8% (bottom) after 6 months of treatment in the BBI group (Basal-Bolus), the fixed-combo group (basal insulin [BI] + GLP-1RA) and the gliflo-combo group (BI + Gliflozin).
Figure 2
Figure 2
Insulin daily doses (top) and number of injections daily (bottom) after 6 months of treatment in the BBI group (Basal-Bolus), the fixed-combo group (basal insulin [BI] + GLP-1RA) and the gliflo-combo group (BI + Gliflozin).

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