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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.

ABSTRACT: 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. 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. 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. 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.

SUBMITTER: Giugliano D

PROVIDER: S-EPMC8247516 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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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.

Giugliano Dario D Longo Miriam M Caruso Paola P Di Fraia Rosa R Scappaticcio Lorenzo L Gicchino Maurizio M Petrizzo Michela M Bellastella Giuseppe G Maiorino Maria Ida MI Esposito Katherine K

Diabetes care 20210421 6

<h4>Objective</h4>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.<h4>Research design and methods</h4>Participants were randomized (1:1:1) to: <i>1</i>) intensification of the BBI regimen (<i>n</i> = 101), <i>2</i>) fixed ratio of basal ...[more]

PMID: 33883195

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Project description:Type 2 diabetes (T2D) is a progressive disease affecting glucose regulation and a major cause of morbidity and mortality globally. Many patients are not escalated up the treatment ladder appropriately despite failing to achieve glycemic control, with barriers such as fear of hypoglycemia, weight gain, and treatment burden recognized as factors. Exogenous basal insulin is titrated to address control of fasting plasma glucose and may preserve residual β-cell function, thus promoting a greater endogenous prandial insulin response. Native glucagon-like peptide-1 (GLP-1) is a peptide hormone secreted by the gut in response to nutrient ingestion; it increases insulin secretion, inhibits glucagon secretion, and prolongs gastric emptying, thereby lowering overall food intake. As its glucose-lowering action is glucose dependent, a GLP-1 receptor agonist (GLP-1RA) achieves these benefits with a lower risk of hypoglycemia compared with other diabetes therapies. Two products, an insulin degludec/liraglutide combination (IDegLira) and an insulin glargine/lixisenatide combination (IGlarLixi), were approved for use in adults with T2D by the US Food and Drug Administration in 2016. The efficacy and safety of these two basal insulin/GLP-1RA combination products were studied in the DUAL program (NCTs 01336023, 01392573, 01676116, 01618162, 01952145, and 02298192) and the LixiLan program (NCTs 02058160 and 02058147). Compared with basal insulin, insulin/GLP-1RA fixed-ratio combinations are superior at reducing HbA1c with weight neutrality or weight loss rather than weight gain, as well as reduced hypoglycemia rates, and reduced insulin-dose requirement with IDegLira. A combination of different medications may often be required to achieve glycemic control, and fixed-ratio combination products allow such therapies to be given in simple regimens. Clinical trial data for these products highlight the great potential of these agents, not merely their efficacy and safety but also their ease of use and decreased injection burden for patients.

Project description:IntroductionTo date, there have been few head-to-head comparisons between semaglutide once-weekly (OW) and short-acting meal-time insulin in participants with type 2 diabetes (T2D) treated with basal insulin and requiring treatment intensification. This indirect comparison evaluated the effects of these regimens on glycated haemoglobin (HbA1c), body weight, hypoglycaemia, and other clinically relevant outcomes.MethodsA post-hoc, unanchored, individual participant data meta-analysis was conducted on the basis of data from single treatment arms in the SUSTAIN 5 and DUAL 7 trials. Semaglutide 0.5 mg OW and 1.0 mg OW plus basal insulin were compared with an optimised (treat-to-target) basal-bolus regimen of insulin glargine and insulin aspart over 26 weeks, using regression adjustment to account for baseline differences between the trials.ResultsOver 26 weeks, semaglutide 1.0 mg OW plus basal insulin reduced mean HbA1c by significantly more than the basal-bolus regimen (treatment difference: - 0.36%; p = 0.003), while semaglutide 0.5 mg OW plus basal insulin was comparable with basal-bolus insulin (treatment difference: 0.08%, p = 0.53). Both doses of semaglutide were associated with significant weight loss relative to insulin intensification (treatment differences: 6.8-9.4 kg; p < 0.001). At both doses, semaglutide intensification required less basal insulin per day than bolus intensification, and more participants on semaglutide met HbA1c targets of < 7.0% and ≤ 6.5% without hypoglycaemia or weight gain (odds ratio [OR] for < 7.0%, 21.9; OR for ≤ 6.5%, 16.2; both p < 0.001).ConclusionsIn T2D uncontrolled by basal insulin, intensification with semaglutide 1.0 mg OW was associated with better glycaemic control, weight loss, and reduced hypoglycaemia versus a basal-bolus regimen, while limiting the treatment burden associated with frequent injections. Clinicians could consider treatment intensification with semaglutide when T2D is uncontrolled by basal insulin, especially when weight management is a priority. Effective glycaemic control coupled with weight management can alleviate the burden of diabetes-associated complications.

Dataset Information

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.

Publications

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.

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