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

Helena W Rodbard
Helena W Rodbard
University of Texas Southwestern Medical School
United States
Ildiko Lingvay
Ildiko Lingvay
University of Texas Southwestern Medical Center
John Reed
John Reed
Sanford-Burnham Medical Research Institute
United States
Danny Sugimoto
Danny Sugimoto
Cedar-Crosse Research Center
Eiichi Araki
Eiichi Araki
Kumamoto University

J Clin Endocrinol Metab 2018 06;103(6):2291-2301

University of California at San Francisco, Fresno, California.

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 (HbA1c) from baseline to week 30. Confirmatory secondary endpoint was change in body weight from baseline to week 30.

Results: At week 30, mean HbA1c 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 HbA1c and body weight in patients with uncontrolled T2D vs placebo.

Download full-text PDF

Source Listing
June 2018
31 Reads
3 Citations
6.210 Impact Factor

Publication Analysis

Top Keywords

basal insulin
body weight
semaglutide placebo
patients events
uncontrolled t2d
mmol/mol 95%
estimated rate
add-on basal
rate ratio
ratio placebo
patients uncontrolled
baseline week
type diabetes
endpoint change
semaglutide basal

Altmetric Statistics


(Supplied by CrossRef)
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)
UK Prospective Diabetes Study (UKPDS) Group et al.
Lancet 1998
Patient adherence to medication requirements for therapy of type 2 diabetes
Bailey et al.
Int J Clin Pract 2011
10-year follow-up of intensive glucose control in type 2 diabetes
Holman et al.
N Engl J Med 2008
Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study
Ohkubo et al.
Diabetes Res Clin Pract 1995
Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study
Stratton et al.
BMJ 2000
Insulin therapy for type 2 diabetes
Swinnen et al.
Diabetes Care 2009
GLP-1 receptor activated insulin secretion from pancreatic β-cells: mechanism and glucose dependence
Meloni et al.
Diabetes Obes Metab 2013
The effect of glucagon-like peptide 1 receptor agonists on weight loss in type 2 diabetes: a systematic review and mixed treatment comparison meta-analysis
Potts et al.
PLoS One 2015
Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans
Flint et al.
J Clin Invest 1998
Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial
Buse et al.
Ann Intern Med 2011
Randomized, double-blind, placebo-controlled trial of the once-daily GLP-1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea (GetGoal-L-Asia)
Seino et al.
Diabetes Obes Metab 2012

Similar Publications