A randomized trial comparing the efficacy and safety of treating patients with type 2 diabetes and highly elevated HbA1c levels with basal‐bolus insulin or a glucagon‐like peptide‐1 receptor agonist plus basal insulin: The SIMPLE study

Abstract

Aim: To compare the efficacy and safety of a glucagon-like peptide-1 receptor agonist (GLP1RA) plus basal insulin versus basal-bolus insulin treatment in patients with very uncontrolled type 2 diabetes. Materials and methods:The SIMPLE study was a 6-month pragmatic, randomized, open-label trial testing the effectiveness of two approaches to treat patients with type 2 diabetes and HbA1c ≥10%. We randomized patients to detemir plus liraglutide or detemir plus aspart (before each meal). The primary endpoint was change in HbA1c; changes in body weight, insulin dose, hypoglycaemia and diabetes-related quality-of-life were secondary outcomes.Results: We randomized 120 participants aged 47.4 ± 9.5 years, Hispanic 40%, African American 42%, diabetes duration 10 [25th-75th percentile (6 to 15)] years, body mass index 37.2 ± 10.3 kg/m 2 . HbA1c decreased more with GLP1RA plus basal insulin [12.2% (95% CI 11.8% to 12.6%) to 8.1% (95% CI 7.4% to 8.7%)] compared with basal-bolus insulin [11.8% (95% CI 11.5% to 12.2%) to 8.8% (95% CI 88.1% to 9.55%)]; estimated treatment difference (ETD) of −1.1% (95% CI −2.0% to −0.1%) (non-inferiority margin 0.4% and P = .0001, superiority P = .026). Compared with basal-bolus insulin, treatment with GLP1RA plus basal insulin led to a body weight ETD of −3.7 kg (95% CI −5.8 to −1.5; P = .001), fewer patients experiencing hypoglycaemia [66.1% vs 35.2% (P = .002)], and greater improvements in general/current health perception, treatment satisfaction, and fear of hypoglycaemia, while taking a lower total daily dose of insulin [estimated treatment ratio 0.68 (95% CI 0.55 to 0.84)].Conclusions: In patients with HbA1c ≥10% treatment with GLP1RA plus basal insulin, compared with basal-bolus insulin, resulted in better glycaemic control and body weight, lower insulin dosage and hypoglycaemia, and improved quality of life. This treatment strategy is an effective and safe alternative to a basal-bolus insulin regimen.

Effect of medication adherence on clinical outcomes in type 2 diabetes: analysis of the SIMPLE study

“…This is an analysis of the SIMPLE study, which was a prospective, randomized, open-label, parallel group trial comparing two treatment strategies (GLP1RA+BI vs BBI), both in addition to metformin in individuals with very uncontrolled (HbA1c≥10%) T2D. The intention-to-treat data set of the SIMPLE trial included n=110 with 54 patients in GLP1RA+BI group and 56 patients in the BBI group 18…”

“…The dose was titrated to maximum tolerated dose or to 1000 mg twice daily. A full description of the study design, interventions, and outcomes can be found in the primary manuscript 18…”

“…A total of 120 participants were randomized with an average age of 47.4±9.5, diabetes duration of 10.5±7.2 years, and HbA1c 12.1%±1.4%. Treatment with GLP1RA+BI improved HgbA1c more than treatment with BBI regimen (estimated treatment difference (ETD) of −1.1%, 95% CI −2.0% to −0.1%, p=0.03), while this group also had better weight outcomes (ETD −3.7 kg, 95% CI −5.8 to −1.5, p=0.001), lower risk of hypoglycemia (35.2% vs 66.1%, respectively) and greater improvement in several quality of life (QoL) domains 18…”

“…GLP1RAs are potent glucose-lowering agents, and when used in conjunction with insulin they can further improve glycemic control, lower the dose of insulin, and minimize hypoglycemia 13. Combination therapy with a GLP1RA plus basal insulin (GLP1RA+BI) is effective and more convenient compared with either a BBI or even less intense insulin-based regimens like basal-plus one or premixed insulins 14–18. The GLP1RA+BI can be administered at the same time of the day, irrespective of meals, can be easily self-titrated by the patients, and therefore a more desirable treatment strategy compared with other more complex insulin-based regimens, which could also translate to increased adherence to therapy 19…”