Effect of adding liraglutide vs placebo to a high-dose lnsulin regimen in patients with type 2 diabetes a randomized clinical trial

Anna Vanderheiden, Lindsay Harrison, Jeremy Warshauer, Xilong Li, Beverley Adams-Huet, Ildiko Lingvay

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

IMPORTANCE An increasing number of patients with type 2 diabetes are treated with high doses of insulin. Such treatment is associated with weight gain, hypoglycemia, and high treatment burden. OBJECTIVE To assess the effectiveness and safety of adding a glucagon-like peptide 1 receptor agonist to the treatment regimen of patients with type 2 diabetes requiring therapy with high-dose insulin. DESIGN, SETTING, AND PARTICIPANTS This clinical trialwas a double-blind, placebo-controlled, randomized (1:1) study with 6 months of follow-up, conducted from August 13, 2012, to February 9, 2015, at ambulatory clinics at the University of Texas Southwestern Medical Center and Parkland Hospital. Participants were 71 patients with uncontrolled type 2 diabetes (glycated hemoglobin level, 7.5%-11.0%) using more than 1.5 U/kg/d of insulin. INTERVENTIONS Subcutaneous injection of liraglutide (1.8mg/d) or matching placebo for 6 months. MAIN OUTCOMES AND MEASURES The primary outcomewas the change in glycated hemoglobin level. Secondary outcomes were changes in weight, hypoglycemia rate, insulin dosage, and quality-of-life measures. RESULTS Among 71 patients, 45 (63%) were female. The mean (SD) age of patients was 54.2 (7.4) years, with a mean (SD) type 2 diabetes duration of 17.9 (8.4) years and a mean (SD) total daily dose of insulin of 247.0 (95.1) U. Ninety-three percent (66 of 71) of participants completed all scheduled visits. The glycated hemoglobin level improved from a mean (SD) of 9.0% (1.2%) to 7.9% (1.1%) in the liraglutide group (P < .001) and remained unchanged (8.9%) in the placebo group, with an estimated treatment difference of 0.9%(95%CI, -1.5 to -0.4) (P = .002).Weight decreased from a mean (SD) of 114.6 (21.4) kg to 113.6 (20.8) kg in the liraglutide group vs a mean (SD) increase from 116.1 (26.6) kg to 117.2 (27.2) kg in the placebo group, with a treatment difference of -2.3 kg (95%CI, -4.3 to -0.4 kg) (P = .02). The total daily dose of insulin decreased 11.5%(95%CI, -21.8%to -1.1%) in the liraglutide group (P = .20). The hypoglycemia rate was higher in the first month after initiation of liraglutide compared with placebo (2.30 vs 0.91 events per person-month, P = .01), while the overall hypoglycemia rate over the entire follow-up was similar between groups (P = .11). Glycemia control perception, satisfaction with insulin treatment, and willingness to continue insulin use improved more in the liraglutide group. CONCLUSIONS AND RELEVANCE Liraglutide added to high-dose insulin therapy improved glycemic control, decreased body weight, and enhanced treatment satisfaction in this difficult-to-treat patient population with high-dose insulin requirements. Further studies are warranted to confirm these findings and evaluate the long-term risk and benefit of this treatment option.

Original languageEnglish (US)
Pages (from-to)939-947
Number of pages9
JournalJAMA Internal Medicine
Volume176
Issue number7
DOIs
StatePublished - Jul 1 2016

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Type 2 Diabetes Mellitus
Randomized Controlled Trials
Placebos
Insulin
Hypoglycemia
Glycosylated Hemoglobin A
Therapeutics
Liraglutide
Weights and Measures
Subcutaneous Injections
Weight Gain
Body Weight
Quality of Life
Safety

ASJC Scopus subject areas

  • Internal Medicine

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Effect of adding liraglutide vs placebo to a high-dose lnsulin regimen in patients with type 2 diabetes a randomized clinical trial. / Vanderheiden, Anna; Harrison, Lindsay; Warshauer, Jeremy; Li, Xilong; Adams-Huet, Beverley; Lingvay, Ildiko.

In: JAMA Internal Medicine, Vol. 176, No. 7, 01.07.2016, p. 939-947.

Research output: Contribution to journalArticle

Vanderheiden, Anna ; Harrison, Lindsay ; Warshauer, Jeremy ; Li, Xilong ; Adams-Huet, Beverley ; Lingvay, Ildiko. / Effect of adding liraglutide vs placebo to a high-dose lnsulin regimen in patients with type 2 diabetes a randomized clinical trial. In: JAMA Internal Medicine. 2016 ; Vol. 176, No. 7. pp. 939-947.
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abstract = "IMPORTANCE An increasing number of patients with type 2 diabetes are treated with high doses of insulin. Such treatment is associated with weight gain, hypoglycemia, and high treatment burden. OBJECTIVE To assess the effectiveness and safety of adding a glucagon-like peptide 1 receptor agonist to the treatment regimen of patients with type 2 diabetes requiring therapy with high-dose insulin. DESIGN, SETTING, AND PARTICIPANTS This clinical trialwas a double-blind, placebo-controlled, randomized (1:1) study with 6 months of follow-up, conducted from August 13, 2012, to February 9, 2015, at ambulatory clinics at the University of Texas Southwestern Medical Center and Parkland Hospital. Participants were 71 patients with uncontrolled type 2 diabetes (glycated hemoglobin level, 7.5{\%}-11.0{\%}) using more than 1.5 U/kg/d of insulin. INTERVENTIONS Subcutaneous injection of liraglutide (1.8mg/d) or matching placebo for 6 months. MAIN OUTCOMES AND MEASURES The primary outcomewas the change in glycated hemoglobin level. Secondary outcomes were changes in weight, hypoglycemia rate, insulin dosage, and quality-of-life measures. RESULTS Among 71 patients, 45 (63{\%}) were female. The mean (SD) age of patients was 54.2 (7.4) years, with a mean (SD) type 2 diabetes duration of 17.9 (8.4) years and a mean (SD) total daily dose of insulin of 247.0 (95.1) U. Ninety-three percent (66 of 71) of participants completed all scheduled visits. The glycated hemoglobin level improved from a mean (SD) of 9.0{\%} (1.2{\%}) to 7.9{\%} (1.1{\%}) in the liraglutide group (P < .001) and remained unchanged (8.9{\%}) in the placebo group, with an estimated treatment difference of 0.9{\%}(95{\%}CI, -1.5 to -0.4) (P = .002).Weight decreased from a mean (SD) of 114.6 (21.4) kg to 113.6 (20.8) kg in the liraglutide group vs a mean (SD) increase from 116.1 (26.6) kg to 117.2 (27.2) kg in the placebo group, with a treatment difference of -2.3 kg (95{\%}CI, -4.3 to -0.4 kg) (P = .02). The total daily dose of insulin decreased 11.5{\%}(95{\%}CI, -21.8{\%}to -1.1{\%}) in the liraglutide group (P = .20). The hypoglycemia rate was higher in the first month after initiation of liraglutide compared with placebo (2.30 vs 0.91 events per person-month, P = .01), while the overall hypoglycemia rate over the entire follow-up was similar between groups (P = .11). Glycemia control perception, satisfaction with insulin treatment, and willingness to continue insulin use improved more in the liraglutide group. CONCLUSIONS AND RELEVANCE Liraglutide added to high-dose insulin therapy improved glycemic control, decreased body weight, and enhanced treatment satisfaction in this difficult-to-treat patient population with high-dose insulin requirements. Further studies are warranted to confirm these findings and evaluate the long-term risk and benefit of this treatment option.",
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T1 - Effect of adding liraglutide vs placebo to a high-dose lnsulin regimen in patients with type 2 diabetes a randomized clinical trial

AU - Vanderheiden, Anna

AU - Harrison, Lindsay

AU - Warshauer, Jeremy

AU - Li, Xilong

AU - Adams-Huet, Beverley

AU - Lingvay, Ildiko

PY - 2016/7/1

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N2 - IMPORTANCE An increasing number of patients with type 2 diabetes are treated with high doses of insulin. Such treatment is associated with weight gain, hypoglycemia, and high treatment burden. OBJECTIVE To assess the effectiveness and safety of adding a glucagon-like peptide 1 receptor agonist to the treatment regimen of patients with type 2 diabetes requiring therapy with high-dose insulin. DESIGN, SETTING, AND PARTICIPANTS This clinical trialwas a double-blind, placebo-controlled, randomized (1:1) study with 6 months of follow-up, conducted from August 13, 2012, to February 9, 2015, at ambulatory clinics at the University of Texas Southwestern Medical Center and Parkland Hospital. Participants were 71 patients with uncontrolled type 2 diabetes (glycated hemoglobin level, 7.5%-11.0%) using more than 1.5 U/kg/d of insulin. INTERVENTIONS Subcutaneous injection of liraglutide (1.8mg/d) or matching placebo for 6 months. MAIN OUTCOMES AND MEASURES The primary outcomewas the change in glycated hemoglobin level. Secondary outcomes were changes in weight, hypoglycemia rate, insulin dosage, and quality-of-life measures. RESULTS Among 71 patients, 45 (63%) were female. The mean (SD) age of patients was 54.2 (7.4) years, with a mean (SD) type 2 diabetes duration of 17.9 (8.4) years and a mean (SD) total daily dose of insulin of 247.0 (95.1) U. Ninety-three percent (66 of 71) of participants completed all scheduled visits. The glycated hemoglobin level improved from a mean (SD) of 9.0% (1.2%) to 7.9% (1.1%) in the liraglutide group (P < .001) and remained unchanged (8.9%) in the placebo group, with an estimated treatment difference of 0.9%(95%CI, -1.5 to -0.4) (P = .002).Weight decreased from a mean (SD) of 114.6 (21.4) kg to 113.6 (20.8) kg in the liraglutide group vs a mean (SD) increase from 116.1 (26.6) kg to 117.2 (27.2) kg in the placebo group, with a treatment difference of -2.3 kg (95%CI, -4.3 to -0.4 kg) (P = .02). The total daily dose of insulin decreased 11.5%(95%CI, -21.8%to -1.1%) in the liraglutide group (P = .20). The hypoglycemia rate was higher in the first month after initiation of liraglutide compared with placebo (2.30 vs 0.91 events per person-month, P = .01), while the overall hypoglycemia rate over the entire follow-up was similar between groups (P = .11). Glycemia control perception, satisfaction with insulin treatment, and willingness to continue insulin use improved more in the liraglutide group. CONCLUSIONS AND RELEVANCE Liraglutide added to high-dose insulin therapy improved glycemic control, decreased body weight, and enhanced treatment satisfaction in this difficult-to-treat patient population with high-dose insulin requirements. Further studies are warranted to confirm these findings and evaluate the long-term risk and benefit of this treatment option.

AB - IMPORTANCE An increasing number of patients with type 2 diabetes are treated with high doses of insulin. Such treatment is associated with weight gain, hypoglycemia, and high treatment burden. OBJECTIVE To assess the effectiveness and safety of adding a glucagon-like peptide 1 receptor agonist to the treatment regimen of patients with type 2 diabetes requiring therapy with high-dose insulin. DESIGN, SETTING, AND PARTICIPANTS This clinical trialwas a double-blind, placebo-controlled, randomized (1:1) study with 6 months of follow-up, conducted from August 13, 2012, to February 9, 2015, at ambulatory clinics at the University of Texas Southwestern Medical Center and Parkland Hospital. Participants were 71 patients with uncontrolled type 2 diabetes (glycated hemoglobin level, 7.5%-11.0%) using more than 1.5 U/kg/d of insulin. INTERVENTIONS Subcutaneous injection of liraglutide (1.8mg/d) or matching placebo for 6 months. MAIN OUTCOMES AND MEASURES The primary outcomewas the change in glycated hemoglobin level. Secondary outcomes were changes in weight, hypoglycemia rate, insulin dosage, and quality-of-life measures. RESULTS Among 71 patients, 45 (63%) were female. The mean (SD) age of patients was 54.2 (7.4) years, with a mean (SD) type 2 diabetes duration of 17.9 (8.4) years and a mean (SD) total daily dose of insulin of 247.0 (95.1) U. Ninety-three percent (66 of 71) of participants completed all scheduled visits. The glycated hemoglobin level improved from a mean (SD) of 9.0% (1.2%) to 7.9% (1.1%) in the liraglutide group (P < .001) and remained unchanged (8.9%) in the placebo group, with an estimated treatment difference of 0.9%(95%CI, -1.5 to -0.4) (P = .002).Weight decreased from a mean (SD) of 114.6 (21.4) kg to 113.6 (20.8) kg in the liraglutide group vs a mean (SD) increase from 116.1 (26.6) kg to 117.2 (27.2) kg in the placebo group, with a treatment difference of -2.3 kg (95%CI, -4.3 to -0.4 kg) (P = .02). The total daily dose of insulin decreased 11.5%(95%CI, -21.8%to -1.1%) in the liraglutide group (P = .20). The hypoglycemia rate was higher in the first month after initiation of liraglutide compared with placebo (2.30 vs 0.91 events per person-month, P = .01), while the overall hypoglycemia rate over the entire follow-up was similar between groups (P = .11). Glycemia control perception, satisfaction with insulin treatment, and willingness to continue insulin use improved more in the liraglutide group. CONCLUSIONS AND RELEVANCE Liraglutide added to high-dose insulin therapy improved glycemic control, decreased body weight, and enhanced treatment satisfaction in this difficult-to-treat patient population with high-dose insulin requirements. Further studies are warranted to confirm these findings and evaluate the long-term risk and benefit of this treatment option.

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