BEYOND (Durability of Combination of Insulin and GLP-1 Receptor Agonist or SGLT2 Inhibitors Versus Basal–Bolus Insulin Regimen in Type 2 Diabetes) was a pragmatic, single-centre, 6-month, open-label, randomised controlled trial to evaluate the effects of switching from a basal–bolus (BB) insulin regimen to either a fixed-dose combination of basal insulin plus a glucagon-like peptide-1 receptor agonist (GLP-1RA) or to a combination of basal insulin plus a sodium–glucose cotransporter 2 inhibitor (SGLT2i).
A total of 305 people with type 2 diabetes with inadequate glycaemic control (HbA1c >58 mmol/mol [7.5%]) despite being on a BB regimen (four injections per day) were randomised 1:1:1 to either intensification of their BB regimen, the basal/GLP-1RA combination (one daily injection) or to the basal/SGLT2i combination (one bedtime injection plus one pill with the main meal per day).
At 6 months, mean HbA1c had fallen by 6.6, 6.6 and 7.7 mmol/mol in the BB, GLP-1RA and SGLT2i groups, respectively, with no significant difference between the groups. Likewise, the proportions of participants achieving various HbA1c targets and a ≥5.5 mmol/mol HbA1c reduction were all similar between the groups. Fasting plasma glucose levels fell significantly in the BB and GLP-1RA groups, but not in the SGLT2i group. Body weight decreased significantly in the GLP-1RA group only (by 1.9 kg). Diabetes Treatment Satisfaction Questionnaire scores increased significantly by 16.8 and 17.9 points in the GLP-1RA and SGLT2i groups, respectively, but remained unchanged in the BB group.
Level 1 hypoglycaemia occurred in 17.8%, 7.8% and 5.9% of participants in the BB, GLP-1RA and SGLT2i groups, respectively. Less than 5% of participants in each group experienced level 2 or 3 hypoglycaemia. Four participants in the GLP-1RA group discontinued owing to gastrointestinal side effects, and three discontinued from the SGLT2i group owing to genital mycotic infections. A further eight in the GLP-1RA group and six in the SGLT2i group discontinued due to inefficacy at 3 months.
Within the intervention groups, participants were randomised to different drugs within the GLP-1RA and SGLT2i classes. No differences in outcomes were observed between the different drug brands.
The authors conclude that, in people with type 2 diabetes who are not achieving optimal glycaemic control on a BB insulin regimen, simplifying to either a fixed-dose insulin/GLP-1RA combination or to an insulin/SGLT2i combination achieves similar glycaemic control to intensification of the BB regimen, with the added benefit of fewer injections and lower insulin doses, less hypoglycaemia, higher treatment satisfaction and, in the case of the insulin/GLP-1RA combination, weight loss. The BEYOND study has been extended and is scheduled to report outcomes at 2 years.
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