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
N1 - Funding Information:
Disclosure Summary: H.W.R. has received grant support andfeesforconsultancyfromAstraZeneca,BoehringerIngelheim, Janssen, Lilly, Novo Nordisk and Sanofi. I.L. has received grant support from GI Dynamics, Merck, Novartis, Novo Nordisk, and Pfizer; travel and editorial support from Novo Nordisk; and editorial support from AstraZeneca, Boehringer Ingelheim, and Sanofi. J.R. has received research support from Novo Nordisk; Eli Lilly; Sanofi; Takeda; Bristol Myers Squibb; Diasome; Gann & Lee; Kowa; Calibra Medical, Inc.; Amylin, Medtronic; EISAI; Biodel; Johnson & Johnson; Amgen; Wyeth; Novartis; Dexcom; and Pfizer. R.d.l.R. has received grant support, speaker fees, and medical writing support from Novo Nordisk; grant support and speaker fees from Sanofi Aventis; speaker fees from Boehringer Ingelheim;andgrantsupportfromAmylin,ElcelyxTherapeutics, GlaxoSmithKline, Intarcia Therapeutics, Merck, and Theracos. D.S. has received grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Elcelyx Therapeutics, Ligand Pharmaceuticals, Merck, Novo Nordisk, Roche, Sanofi, and Takeda and has received medical writing support from Novo Nordisk and Sanofi. L.R. has received grants and personal fees from Astra-Zeneca, Lilly, and Novo Nordisk. E.A. has received research support or grants and/or personal fees for lecturing and consulting on advisory boards and has received editorial support from Arkray, Inc.; Astellas Pharma, Inc.; AstraZeneca KK; Bayer Yakuhin Ltd; Bunkodo Co. Ltd; Daido Gakkan; Daiichi Sankyo; Eli Lilly Japan KK; Kissei Pharmaceutical Co.; Kowa Pharmaceutical Co. Ltd; Kyowa Hakko Kirin Co. Ltd; Kyowa Kikaku Ltd; Medical Review Co. Ltd; Mochida Pharmaceutical Co. Ltd.; Mitsubishi Tanabe Pharma Corporation; MSD; Nankodo Co. Ltd; Nippon Boehringer Ingelheim; Novartis Pharma KK; Novo Nordisk; Ono Pharmaceutical; Sanofi KK; Sanwa Kagaku Kenkyusho Co.; Shionogi & Co. Ltd; Sumitomo Dainippon Pharma Co.; Taisho Toyama Pharmaceutical Co. Ltd.; Takeda Pharmaceutical Company; T-Pec Corporation; and Wiley Publishing Japan Co. Ltd. P.-L.C. reports being an employee of Novo NordiskInc.whilethetrialwasconducted.N.W.reportsbeingan employee of Novo Nordisk A/S. P.N. reports receiving research support from Novo Nordisk.
Funding Information:
Financial Support: This study was funded by Novo Nordisk A/S.
Publisher Copyright:
© 2018 Endocrine Society.
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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U2 - 10.1210/jc.2018-00070
DO - 10.1210/jc.2018-00070
M3 - Article
C2 - 29688502
AN - SCOPUS:85048662846
VL - 103
SP - 2291
EP - 2301
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 6
ER -