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 A Huet, Xilong Li, Ildiko Lingvay

Research output: Contribution to journalArticle

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/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
DOIs
StatePublished - Jan 1 2019

Fingerprint

Patient Safety
Type 2 Diabetes Mellitus
Insulin
Hypoglycemia
Therapeutics
Glucagon-Like Peptide-1 Receptor
Body Weight
Quality of Life
Body Weight Changes
Hispanic Americans
African Americans
Fear
Meals
Body Mass Index
Safety

Keywords

  • liraglutide
  • type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

@article{193940ca29a243a3afc710e7e3225302,
title = "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",
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/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.",
keywords = "liraglutide, type 2 diabetes",
author = "Marconi Abreu and Anna Tumyan and Ahmed Elhassan and Katherine Peicher and Olivia Papacostea and Perihan Dimachkie and Siddiqui, {Muhammad S.} and Pop, {Laurentiu M} and Uma Gunasekaran and Meneghini, {Luigi F} and Huet, {Beverley A} and Xilong Li and Ildiko Lingvay",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/dom.13794",
language = "English (US)",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - 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

T2 - The SIMPLE study

AU - Abreu, Marconi

AU - Tumyan, Anna

AU - Elhassan, Ahmed

AU - Peicher, Katherine

AU - Papacostea, Olivia

AU - Dimachkie, Perihan

AU - Siddiqui, Muhammad S.

AU - Pop, Laurentiu M

AU - Gunasekaran, Uma

AU - Meneghini, Luigi F

AU - Huet, Beverley A

AU - Li, Xilong

AU - Lingvay, Ildiko

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - liraglutide

KW - type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85068327094&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068327094&partnerID=8YFLogxK

U2 - 10.1111/dom.13794

DO - 10.1111/dom.13794

M3 - Article

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

ER -