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-bolus insulin: The SIMPLE study

Marconi Abreu, Anna Tumyan, Ahmed Elhassan, Katherine Peicher, Olivia Papacostea, Perihan Dimachkie, Muhammad S. Siddiqui, Laurentiu M. Pop, Uma Gunasekaran, Luigi F. Meneghini, Beverley Adams-Huet, Xilong Li, Ildiko Lingvay

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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/m2. 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.

Original languageEnglish (US)
JournalDiabetes, Obesity and Metabolism
StatePublished - Jan 1 2019



  • liraglutide
  • type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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