Basal insulin plus GLP-1 RA or SGLT2 inhibitor was noninferior to basal-bolus insulin intensification for HbA1c in T2DM

A recent Italian trial showed that regimens with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or a sodium-glucose cotransporter 2 (SGLT2) inhibitor resulted in less hypoglycemia, but the results may not apply to patients with higher HbA1c levels, an ACP Journal Club commentary said.

It was feasible to switch some patients with inadequately controlled type 2 diabetes from basal-bolus insulin (BBI) to a simpler regimen including either a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or a sodium-glucose cotransporter 2 (SGLT2) inhibitor, according to a recent study. The six-month trial found similar improvements in HbA1c among patients randomized to intensified BBI (n=101), a fixed ratio of basal insulin plus a GLP-1 RA (n=102), or a combination of basal insulin plus a SGLT2 inhibitor (n=102), with fewer insulin doses in the GLP-1RA and SGLT2 groups.

The study was published by Diabetes Care on April 21. The following commentary by Miranda K. Boggild, MD, MScCH, and Angela M. Cheung, MD, PhD, was published in the ACP Journal Club section of Annals of Internal Medicine on Sept. 7.

The trial by Giugliano and colleagues showed that in patients with T2DM inadequately controlled by BBI, discontinuing bolus insulin and starting a GLP-1 RA or a SGLT2 inhibitor were both noninferior to BBI intensification. The pragmatic BEYOND trial helps inform the next steps for this common clinical scenario. While switching to fixed combination or gliflozin combination was noninferior to BBI intensification for glycemic control, both groups had less hypoglycemia and greater patient satisfaction than the BBI group, and the fixed-combination group had more weight loss than the BBI group.

Mean baseline HbA1c was 8.5% to 8.7%, so these results may not apply to patients with more severe hyperglycemia. Gradual weaning of bolus insulin instead of discontinuation may be preferable in patients with higher HbA1c or higher insulin needs at baseline. The fixed- and gliflozin-combination groups had more dropouts than the BBI intensification group; most were due to inefficacy in maintaining HbA1c below baseline at 3 months. This suggests that these regimens may not be effective for all patients and reassessment at 3 months is important.

This trial does not address which of the 2 combination regimens is better for a given patient. Treatment decisions depend on patient characteristics and preferences, including comorbidities, contraindications, and drug side effects and costs. Generalizability to non-White populations is limited as the trial was done at a single center in Italy.

Despite these limitations, the BEYOND trial showed that switching from a 4-dose insulin regimen to a more simplified single dose of fixed-ratio basal insulin with GLP-1 RA or basal insulin with an oral SGLT2 inhibitor was as effective as BBI intensification for lowering HbA1c, with less hypoglycemia. Longer follow-up will shed more light on the benefits of these regimens on clinical outcomes.