Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5): A Randomized, Controlled Trial

Helena W. Rodbard, Ildiko Lingvay, John Reed, Raymond De La Rosa, Ludger Rose, Danny Sugimoto, Eiichi Araki, Pei Ling Chu, Nelun Wijayasinghe, Paul Norwood

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Context Combination therapy with insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is important for treating type 2 diabetes (T2D). This trial assesses the efficacy and safety of semaglutide, a GLP-1RA, as an add-on to basal insulin. Objective To demonstrate the superiority of semaglutide vs placebo on glycemic control as an add-on to basal insulin in patients with T2D. Design Phase 3a, double-blind, placebo-controlled, 30-week trial. Setting This study included 90 sites in five countries. Patients We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin. Interventions Subcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo. Main Outcome Measures Primary endpoint was change in glycated Hb (HbA 1c) from baseline to week 30. Confirmatory secondary endpoint was change in body weight from baseline to week 30. Results At week 30, mean HbA 1c reductions [mean baseline value, 8.4% (67.9 mmol/mol)] with semaglutide 0.5 and 1.0 mg were 1.4% (15.8 mmol/mol) and 1.8% (20.2 mmol/mol) vs 0.1% (1.0 mmol/mol) with placebo [estimated treatment difference (ETD) vs placebo, -1.35 (14.8 mmol/mol); 95% CI, -1.61 to -1.10 and ETD, -1.75% (19.2 mmol/mol); 95% CI, -2.01 to -1.50; both P < 0.0001]. Severe or blood glucose-confirmed hypoglycemic episodes were reported in 11 patients (17 events) and 14 patients (25 events) with semaglutide 0.5 and 1.0 mg, respectively, vs seven patients (13 events) with placebo (estimated rate ratio vs placebo, 2.08; 95% CI, 0.67 to 6.51 and estimated rate ratio vs placebo, 2.41; 95% CI, 0.84 to 6.96 for 0.5 and 1.0 mg; both P = nonsignificant). Mean body weight decreased with semaglutide 0.5 and 1.0 mg vs placebo from baseline to end of treatment: 3.7, 6.4, and 1.4 kg (ETD, -2.31; 95% CI, -3.33 to -1.29 and ETD, -5.06; 95% CI, -6.08 to -4.04 kg; both P < 0.0001). Premature treatment discontinuation due to adverse events was higher for semaglutide 0.5 and 1.0 mg vs placebo (4.5%, 6.1%, and 0.8%), mainly due to gastrointestinal disorders. Conclusions Semaglutide, added to basal insulin, significantly reduced HbA 1c and body weight in patients with uncontrolled T2D vs placebo.

Original languageEnglish (US)
Pages (from-to)2291-2301
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume103
Issue number6
DOIs
StatePublished - Jun 1 2018

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Medical problems
Type 2 Diabetes Mellitus
Randomized Controlled Trials
Placebos
Insulin
Therapeutics
semaglutide
Metformin
Body Weight
Hypoglycemic Agents
Body Weight Changes
Blood Glucose
Outcome Assessment (Health Care)
Safety

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5) : A Randomized, Controlled Trial. / Rodbard, Helena W.; Lingvay, Ildiko; Reed, John; De La Rosa, Raymond; Rose, Ludger; Sugimoto, Danny; Araki, Eiichi; Chu, Pei Ling; Wijayasinghe, Nelun; Norwood, Paul.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 103, No. 6, 01.06.2018, p. 2291-2301.

Research output: Contribution to journalArticle

Rodbard, HW, Lingvay, I, Reed, J, De La Rosa, R, Rose, L, Sugimoto, D, Araki, E, Chu, PL, Wijayasinghe, N & Norwood, P 2018, 'Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5): A Randomized, Controlled Trial', Journal of Clinical Endocrinology and Metabolism, vol. 103, no. 6, pp. 2291-2301. https://doi.org/10.1210/jc.2018-00070
Rodbard, Helena W. ; Lingvay, Ildiko ; Reed, John ; De La Rosa, Raymond ; Rose, Ludger ; Sugimoto, Danny ; Araki, Eiichi ; Chu, Pei Ling ; Wijayasinghe, Nelun ; Norwood, Paul. / Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5) : A Randomized, Controlled Trial. In: Journal of Clinical Endocrinology and Metabolism. 2018 ; Vol. 103, No. 6. pp. 2291-2301.
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abstract = "Context Combination therapy with insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is important for treating type 2 diabetes (T2D). This trial assesses the efficacy and safety of semaglutide, a GLP-1RA, as an add-on to basal insulin. Objective To demonstrate the superiority of semaglutide vs placebo on glycemic control as an add-on to basal insulin in patients with T2D. Design Phase 3a, double-blind, placebo-controlled, 30-week trial. Setting This study included 90 sites in five countries. Patients We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin. Interventions Subcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo. Main Outcome Measures Primary endpoint was change in glycated Hb (HbA 1c) from baseline to week 30. Confirmatory secondary endpoint was change in body weight from baseline to week 30. Results At week 30, mean HbA 1c reductions [mean baseline value, 8.4{\%} (67.9 mmol/mol)] with semaglutide 0.5 and 1.0 mg were 1.4{\%} (15.8 mmol/mol) and 1.8{\%} (20.2 mmol/mol) vs 0.1{\%} (1.0 mmol/mol) with placebo [estimated treatment difference (ETD) vs placebo, -1.35 (14.8 mmol/mol); 95{\%} CI, -1.61 to -1.10 and ETD, -1.75{\%} (19.2 mmol/mol); 95{\%} CI, -2.01 to -1.50; both P < 0.0001]. Severe or blood glucose-confirmed hypoglycemic episodes were reported in 11 patients (17 events) and 14 patients (25 events) with semaglutide 0.5 and 1.0 mg, respectively, vs seven patients (13 events) with placebo (estimated rate ratio vs placebo, 2.08; 95{\%} CI, 0.67 to 6.51 and estimated rate ratio vs placebo, 2.41; 95{\%} CI, 0.84 to 6.96 for 0.5 and 1.0 mg; both P = nonsignificant). Mean body weight decreased with semaglutide 0.5 and 1.0 mg vs placebo from baseline to end of treatment: 3.7, 6.4, and 1.4 kg (ETD, -2.31; 95{\%} CI, -3.33 to -1.29 and ETD, -5.06; 95{\%} CI, -6.08 to -4.04 kg; both P < 0.0001). Premature treatment discontinuation due to adverse events was higher for semaglutide 0.5 and 1.0 mg vs placebo (4.5{\%}, 6.1{\%}, and 0.8{\%}), mainly due to gastrointestinal disorders. Conclusions Semaglutide, added to basal insulin, significantly reduced HbA 1c and body weight in patients with uncontrolled T2D vs placebo.",
author = "Rodbard, {Helena W.} and Ildiko Lingvay and John Reed and {De La Rosa}, Raymond and Ludger Rose and Danny Sugimoto and Eiichi Araki and Chu, {Pei Ling} and Nelun Wijayasinghe and Paul Norwood",
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TY - JOUR

T1 - Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5)

T2 - A Randomized, Controlled Trial

AU - Rodbard, Helena W.

AU - Lingvay, Ildiko

AU - Reed, John

AU - De La Rosa, Raymond

AU - Rose, Ludger

AU - Sugimoto, Danny

AU - Araki, Eiichi

AU - Chu, Pei Ling

AU - Wijayasinghe, Nelun

AU - Norwood, Paul

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Context Combination therapy with insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is important for treating type 2 diabetes (T2D). This trial assesses the efficacy and safety of semaglutide, a GLP-1RA, as an add-on to basal insulin. Objective To demonstrate the superiority of semaglutide vs placebo on glycemic control as an add-on to basal insulin in patients with T2D. Design Phase 3a, double-blind, placebo-controlled, 30-week trial. Setting This study included 90 sites in five countries. Patients We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin. Interventions Subcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo. Main Outcome Measures Primary endpoint was change in glycated Hb (HbA 1c) from baseline to week 30. Confirmatory secondary endpoint was change in body weight from baseline to week 30. Results At week 30, mean HbA 1c reductions [mean baseline value, 8.4% (67.9 mmol/mol)] with semaglutide 0.5 and 1.0 mg were 1.4% (15.8 mmol/mol) and 1.8% (20.2 mmol/mol) vs 0.1% (1.0 mmol/mol) with placebo [estimated treatment difference (ETD) vs placebo, -1.35 (14.8 mmol/mol); 95% CI, -1.61 to -1.10 and ETD, -1.75% (19.2 mmol/mol); 95% CI, -2.01 to -1.50; both P < 0.0001]. Severe or blood glucose-confirmed hypoglycemic episodes were reported in 11 patients (17 events) and 14 patients (25 events) with semaglutide 0.5 and 1.0 mg, respectively, vs seven patients (13 events) with placebo (estimated rate ratio vs placebo, 2.08; 95% CI, 0.67 to 6.51 and estimated rate ratio vs placebo, 2.41; 95% CI, 0.84 to 6.96 for 0.5 and 1.0 mg; both P = nonsignificant). Mean body weight decreased with semaglutide 0.5 and 1.0 mg vs placebo from baseline to end of treatment: 3.7, 6.4, and 1.4 kg (ETD, -2.31; 95% CI, -3.33 to -1.29 and ETD, -5.06; 95% CI, -6.08 to -4.04 kg; both P < 0.0001). Premature treatment discontinuation due to adverse events was higher for semaglutide 0.5 and 1.0 mg vs placebo (4.5%, 6.1%, and 0.8%), mainly due to gastrointestinal disorders. Conclusions Semaglutide, added to basal insulin, significantly reduced HbA 1c and body weight in patients with uncontrolled T2D vs placebo.

AB - Context Combination therapy with insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is important for treating type 2 diabetes (T2D). This trial assesses the efficacy and safety of semaglutide, a GLP-1RA, as an add-on to basal insulin. Objective To demonstrate the superiority of semaglutide vs placebo on glycemic control as an add-on to basal insulin in patients with T2D. Design Phase 3a, double-blind, placebo-controlled, 30-week trial. Setting This study included 90 sites in five countries. Patients We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin. Interventions Subcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo. Main Outcome Measures Primary endpoint was change in glycated Hb (HbA 1c) from baseline to week 30. Confirmatory secondary endpoint was change in body weight from baseline to week 30. Results At week 30, mean HbA 1c reductions [mean baseline value, 8.4% (67.9 mmol/mol)] with semaglutide 0.5 and 1.0 mg were 1.4% (15.8 mmol/mol) and 1.8% (20.2 mmol/mol) vs 0.1% (1.0 mmol/mol) with placebo [estimated treatment difference (ETD) vs placebo, -1.35 (14.8 mmol/mol); 95% CI, -1.61 to -1.10 and ETD, -1.75% (19.2 mmol/mol); 95% CI, -2.01 to -1.50; both P < 0.0001]. Severe or blood glucose-confirmed hypoglycemic episodes were reported in 11 patients (17 events) and 14 patients (25 events) with semaglutide 0.5 and 1.0 mg, respectively, vs seven patients (13 events) with placebo (estimated rate ratio vs placebo, 2.08; 95% CI, 0.67 to 6.51 and estimated rate ratio vs placebo, 2.41; 95% CI, 0.84 to 6.96 for 0.5 and 1.0 mg; both P = nonsignificant). Mean body weight decreased with semaglutide 0.5 and 1.0 mg vs placebo from baseline to end of treatment: 3.7, 6.4, and 1.4 kg (ETD, -2.31; 95% CI, -3.33 to -1.29 and ETD, -5.06; 95% CI, -6.08 to -4.04 kg; both P < 0.0001). Premature treatment discontinuation due to adverse events was higher for semaglutide 0.5 and 1.0 mg vs placebo (4.5%, 6.1%, and 0.8%), mainly due to gastrointestinal disorders. Conclusions Semaglutide, added to basal insulin, significantly reduced HbA 1c and body weight in patients with uncontrolled T2D vs placebo.

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