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

Rodbard HW, Lingvay I, Reed J, de la Rosa R, Rose L, Sugimoto D, Araki E, Chu PL, Wijayasinghe N, Norwood P

The Journal of clinical endocrinology and metabolism1 Jun 2018Cited by 315 (Europe PMC)

PMID29688502PMCIDPMC5991220DOI10.1210/jc.2018-00070PepBankPUB-29688502

Summary

ContextCombination 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.ObjectiveTo demonstrate the superiority of semaglutide vs placebo on glycemic control as an add-on to basal insulin in patients with T2D.DesignPhase 3a, double-blind, placebo-controlled, 30-week trial.SettingThis study included 90 sites in five countries.PatientsWe studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin.InterventionsSubcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo.Main outcome measuresPrimary 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.ResultsAt 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.ConclusionsSemaglutide, added to basal insulin, significantly reduced HbA1c and body weight in patients with uncontrolled T2D vs placebo.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. 8 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with uncontrolled type 2 diabetes on basal insulin, semaglutide 0.5 mg lowered HbA1c more than placebo at week 30.
In plain wordsIn adults with type 2 diabetes on basal insulin, semaglutide 0.5 mg lowered HbA1c more than placebo.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change at week 30
Study
n = 397
Comparator
Placebo
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
0.5 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Measurements
HbA1c change
−1.4%
semaglutide 0.5 mg
HbA1c change
−0.1%
placebo
Estimated treatment difference
−1.35%
vs placebo
Source sentences
Summary
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].
1 context sentence(design, population, supporting numbers)
Summary · context
We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin.InterventionsSubcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo.
Show in the study text Report a problemFND-2968850201
02HumanRandomized controlled trialEfficacy outcome
In adults with uncontrolled type 2 diabetes on basal insulin, semaglutide 1.0 mg lowered HbA1c more than placebo at week 30.
In plain wordsIn adults with type 2 diabetes on basal insulin, semaglutide 1.0 mg lowered HbA1c more than placebo.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change at week 30
Study
n = 397
Comparator
Placebo
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.0 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Measurements
HbA1c change
−1.8%
semaglutide 1.0 mg
HbA1c change
−0.1%
placebo
Estimated treatment difference
−1.75%
vs placebo
Source sentences
Summary
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].
1 context sentence(design, population, supporting numbers)
Summary · context
We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin.InterventionsSubcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo.
Show in the study text Report a problemFND-2968850202
03HumanRandomized controlled trialEfficacy outcome
In adults with uncontrolled type 2 diabetes on basal insulin, semaglutide 0.5 mg reduced body weight more than placebo.
In plain wordsIn adults with type 2 diabetes on basal insulin, semaglutide 0.5 mg led to more weight loss than placebo.
Peptide
Semaglutide
Outcome
DecreaseBody weight change at week 30
Study
n = 397
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
0.5 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Measurements
Body weight change
−3.7 kg
semaglutide 0.5 mg
Body weight change
−1.4 kg
placebo
Estimated treatment difference
−2.31 kg
vs placebo
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin.InterventionsSubcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo.
Show in the study text Report a problemFND-2968850205
04HumanRandomized controlled trialEfficacy outcome
In adults with uncontrolled type 2 diabetes on basal insulin, semaglutide 1.0 mg reduced body weight more than placebo.
In plain wordsIn adults with type 2 diabetes on basal insulin, semaglutide 1.0 mg led to more weight loss than placebo.
Peptide
Semaglutide
Outcome
DecreaseBody weight change at week 30
Study
n = 397
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
1.0 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Measurements
Body weight change
−6.4 kg
semaglutide 1.0 mg
Body weight change
−1.4 kg
placebo
Estimated treatment difference
−5.06 kg
vs placebo
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin.InterventionsSubcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo.
Show in the study text Report a problemFND-2968850206
05HumanRandomized controlled trialSafety outcome
Severe or blood glucose-confirmed hypoglycaemia with semaglutide 0.5 mg did not differ significantly from placebo.
In plain wordsLow blood sugar episodes with semaglutide 0.5 mg were not significantly different from placebo.
Peptide
Semaglutide
Outcome
No significant changeSevere or blood glucose-confirmed hypoglycaemia
Study
n = 397
Comparator
Placebo
Outcome group
Adverse events · Metabolic and weight
Studied dose
0.5 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Measurements
Rate ratio vs placebo
2.08 ratio
semaglutide 0.5 mg
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin.InterventionsSubcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo.
Show in the study text Report a problemFND-2968850203
06HumanRandomized controlled trialSafety outcome
Severe or blood glucose-confirmed hypoglycaemia with semaglutide 1.0 mg did not differ significantly from placebo.
In plain wordsLow blood sugar episodes with semaglutide 1.0 mg were not significantly different from placebo.
Peptide
Semaglutide
Outcome
No significant changeSevere or blood glucose-confirmed hypoglycaemia
Study
n = 397
Comparator
Placebo
Outcome group
Adverse events · Metabolic and weight
Studied dose
1.0 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Measurements
Rate ratio vs placebo
2.41 ratio
semaglutide 1.0 mg
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin.InterventionsSubcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo.
Show in the study text Report a problemFND-2968850204
07HumanRandomized controlled trialSafety outcome
Premature treatment discontinuation due to adverse events was higher with semaglutide 0.5 mg than with placebo, mainly due to gastrointestinal disorders.
In plain wordsMore people stopped treatment early because of side effects with semaglutide 0.5 mg than with placebo, mostly stomach and gut problems.
Peptide
Semaglutide
Outcome
IncreasePremature discontinuation due to adverse events
Study
n = 397
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
0.5 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Measurements
Discontinuation due to adverse events
4.5%
semaglutide 0.5 mg
Discontinuation due to adverse events
0.8%
placebo
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin.InterventionsSubcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo.
Show in the study text Report a problemFND-2968850207
08HumanRandomized controlled trialSafety outcome
Premature treatment discontinuation due to adverse events was higher with semaglutide 1.0 mg than with placebo, mainly due to gastrointestinal disorders.
In plain wordsMore people stopped treatment early because of side effects with semaglutide 1.0 mg than with placebo, mostly stomach and gut problems.
Peptide
Semaglutide
Outcome
IncreasePremature discontinuation due to adverse events
Study
n = 397
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
1.0 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Measurements
Discontinuation due to adverse events
6.1%
semaglutide 1.0 mg
Discontinuation due to adverse events
0.8%
placebo
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin.InterventionsSubcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo.
Show in the study text Report a problemFND-2968850208

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT02305381

Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to Basal Insulin Alone or Basal Insulin in Combination With Metformin in Subjects With Type 2 Diabetes

Novo Nordisk A/Sn = 3971 Dec 2014 to 21 Nov 2015

Diabetes · Diabetes Mellitus, Type 2

Trial page ClinicalTrials.govUpdated 11 Jun 2019

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:50 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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