Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial.

Aroda VR, Bain SC, Cariou B, Piletič M, Rose L, Axelsen M, Rowe E, DeVries JH

The lancet. Diabetes & endocrinology23 Mar 2017Cited by 374 (Europe PMC)

PMID28344112DOI10.1016/s2213-8587(17)30085-2PepBankPUB-28344112

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study13

13 results from studies that gave the peptide. 13 results from people.

01HumanRandomized controlled trialEfficacy outcome
In insulin-naive adults with type 2 diabetes on metformin, semaglutide 0·5 mg reduced HbA1c more than insulin glargine at week 30 (difference -0·38%).
In plain wordsIn adults with type 2 diabetes on metformin, weekly semaglutide 0·5 mg lowered HbA1c more than insulin glargine after 30 weeks.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change at week 30
Study
n = 722
Comparator
Insulin glargine
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
0.5 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
0·5 and 1·0 mg semaglutide achieved reductions of 1·21% (95% CI 1·10-1·31) and 1·64% (1·54-1·74), respectively, versus 0·83% (0·73-0·93) with insulin glargine; estimated treatment difference versus insulin glargine -0·38% (95% CI -0·52 to -0·24) with 0·5 mg semaglutide and -0·81% (-0·96 to -0·67) wi…
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea.
Summary · context
We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose…
Report a problemFND-2834411201
02HumanRandomized controlled trialEfficacy outcome
In insulin-naive adults with type 2 diabetes on metformin, semaglutide 1·0 mg reduced HbA1c more than insulin glargine at week 30 (difference -0·81%).
In plain wordsIn adults with type 2 diabetes on metformin, weekly semaglutide 1·0 mg lowered HbA1c more than insulin glargine after 30 weeks.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change at week 30
Study
n = 720
Comparator
Insulin glargine
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.0 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
0·5 and 1·0 mg semaglutide achieved reductions of 1·21% (95% CI 1·10-1·31) and 1·64% (1·54-1·74), respectively, versus 0·83% (0·73-0·93) with insulin glargine; estimated treatment difference versus insulin glargine -0·38% (95% CI -0·52 to -0·24) with 0·5 mg semaglutide and -0·81% (-0·96 to -0·67) wi…
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea.
Summary · context
We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose…
Report a problemFND-2834411202
03HumanRandomized controlled trialEfficacy outcome
In insulin-naive adults with type 2 diabetes on metformin, semaglutide 0·5 mg reduced bodyweight versus a gain with insulin glargine (difference -4·62 kg).
In plain wordsIn adults with type 2 diabetes on metformin, weekly semaglutide 0·5 mg led to weight loss, while insulin glargine led to weight gain.
Peptide
Semaglutide
Outcome
DecreaseBodyweight change at week 30
Study
n = 722
Comparator
Insulin glargine
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
0.5 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
0·5 and 1·0 mg semaglutide achieved weight losses of 3·47 kg (95% CI 3·00-3·93) and 5·17 kg (4·71-5·66), respectively, versus a weight gain of 1·15 kg (0·70-1·61) with insulin glargine; estimated treatment difference versus insulin glargine -4·62 kg (95% CI -5·27 to -3·96) with 0·5 mg semaglutide an…
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea.
Summary · context
We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose…
Report a problemFND-2834411203
04HumanRandomized controlled trialEfficacy outcome
In insulin-naive adults with type 2 diabetes on metformin, semaglutide 1·0 mg reduced bodyweight versus a gain with insulin glargine (difference -6·33 kg).
In plain wordsIn adults with type 2 diabetes on metformin, weekly semaglutide 1·0 mg led to weight loss, while insulin glargine led to weight gain.
Peptide
Semaglutide
Outcome
DecreaseBodyweight change at week 30
Study
n = 720
Comparator
Insulin glargine
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
1.0 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
0·5 and 1·0 mg semaglutide achieved weight losses of 3·47 kg (95% CI 3·00-3·93) and 5·17 kg (4·71-5·66), respectively, versus a weight gain of 1·15 kg (0·70-1·61) with insulin glargine; estimated treatment difference versus insulin glargine -4·62 kg (95% CI -5·27 to -3·96) with 0·5 mg semaglutide an…
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea.
Summary · context
We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose…
Report a problemFND-2834411204
05HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, 14% discontinued semaglutide 0·5 mg prematurely versus 7% with insulin glargine; most discontinuations were due to adverse events.
In plain wordsIn adults with type 2 diabetes, more people stopped semaglutide 0·5 mg early (14%) than insulin glargine (7%), mostly for side effects.
Peptide
Semaglutide
Outcome
IncreasePremature treatment discontinuation
Study
n = 722
Comparator
Insulin glargine
Outcome group
Adverse events · Whole body
Studied dose
0.5 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
49 (14%) participants assigned to 0·5 mg semaglutide discontinued treatment prematurely, compared with 55 (15%) assigned to 1·0 mg semaglutide, and 26 (7%) assigned to insulin glargine.
3 context sentences(design, population, supporting numbers)
Summary · context
Most discontinuations were due to adverse events-mostly gastrointestinal with semaglutide, and others such as skin and subcutaneous tissue disorders (eg, rash, pruritus, and urticaria) with insulin glargine.
Summary · context
Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea.
Summary · context
We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose…
Report a problemFND-2834411205
06HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, severe or confirmed hypoglycaemia was reported by 4% with semaglutide 0·5 mg versus 11% with insulin glargine.
In plain wordsIn adults with type 2 diabetes, low blood sugar events were less common with semaglutide 0·5 mg (4%) than with insulin glargine (11%).
Peptide
Semaglutide
Outcome
DecreaseSevere or blood glucose-confirmed hypoglycaemia
Study
n = 722
Comparator
Insulin glargine
Outcome group
Adverse events · Metabolic and weight
Studied dose
0.5 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
Severe or blood glucose-confirmed hypoglycaemia was reported by 16 (4%) participants with 0·5 mg semaglutide and 20 (6%) with 1·0 mg semaglutide versus 38 (11%) with insulin glargine (p=0·0021 and p=0·0202 for 0·5 mg and 1·0 mg semaglutide vs insulin glargine, respectively).
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea.
Summary · context
We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose…
Report a problemFND-2834411207
07HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, severe hypoglycaemia was reported by two participants (<1%) with semaglutide 0·5 mg and five (1%) with insulin glargine.
In plain wordsIn adults with type 2 diabetes, severe low blood sugar was rare with semaglutide 0·5 mg and with insulin glargine.
Peptide
Semaglutide
Outcome
No significant changeSevere hypoglycaemia
Study
n = 722
Comparator
Insulin glargine
Outcome group
Adverse events · Metabolic and weight
Studied dose
0.5 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
Severe hypoglycaemia was reported by two (<1%) participants with 0·5 mg semaglutide, five (1%) with 1·0 mg semaglutide, and five (1%) with insulin glargine.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea.
Summary · context
We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose…
Report a problemFND-2834411209
08HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, 15% discontinued semaglutide 1·0 mg prematurely versus 7% with insulin glargine; most discontinuations were due to adverse events.
In plain wordsIn adults with type 2 diabetes, more people stopped semaglutide 1·0 mg early (15%) than insulin glargine (7%), mostly for side effects.
Peptide
Semaglutide
Outcome
IncreasePremature treatment discontinuation
Study
n = 720
Comparator
Insulin glargine
Outcome group
Adverse events · Whole body
Studied dose
1.0 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
49 (14%) participants assigned to 0·5 mg semaglutide discontinued treatment prematurely, compared with 55 (15%) assigned to 1·0 mg semaglutide, and 26 (7%) assigned to insulin glargine.
3 context sentences(design, population, supporting numbers)
Summary · context
Most discontinuations were due to adverse events-mostly gastrointestinal with semaglutide, and others such as skin and subcutaneous tissue disorders (eg, rash, pruritus, and urticaria) with insulin glargine.
Summary · context
Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea.
Summary · context
We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose…
Report a problemFND-2834411206
09HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, severe or confirmed hypoglycaemia was reported by 6% with semaglutide 1·0 mg versus 11% with insulin glargine.
In plain wordsIn adults with type 2 diabetes, low blood sugar events were less common with semaglutide 1·0 mg (6%) than with insulin glargine (11%).
Peptide
Semaglutide
Outcome
DecreaseSevere or blood glucose-confirmed hypoglycaemia
Study
n = 720
Comparator
Insulin glargine
Outcome group
Adverse events · Metabolic and weight
Studied dose
1.0 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
Severe or blood glucose-confirmed hypoglycaemia was reported by 16 (4%) participants with 0·5 mg semaglutide and 20 (6%) with 1·0 mg semaglutide versus 38 (11%) with insulin glargine (p=0·0021 and p=0·0202 for 0·5 mg and 1·0 mg semaglutide vs insulin glargine, respectively).
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea.
Summary · context
We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose…
Report a problemFND-2834411208
10HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, severe hypoglycaemia was reported by five participants (1%) with semaglutide 1·0 mg and five (1%) with insulin glargine.
In plain wordsIn adults with type 2 diabetes, severe low blood sugar was rare with semaglutide 1·0 mg and with insulin glargine.
Peptide
Semaglutide
Outcome
No significant changeSevere hypoglycaemia
Study
n = 720
Comparator
Insulin glargine
Outcome group
Adverse events · Metabolic and weight
Studied dose
1.0 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
Severe hypoglycaemia was reported by two (<1%) participants with 0·5 mg semaglutide, five (1%) with 1·0 mg semaglutide, and five (1%) with insulin glargine.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea.
Summary · context
We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose…
Report a problemFND-2834411210
11HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, four deaths (1%) occurred in the semaglutide 0·5 mg group: three cardiovascular and one pancreatic carcinoma, assessed as possibly related to study medication.
In plain wordsIn adults with type 2 diabetes, four people on semaglutide 0·5 mg died; one pancreatic cancer death was judged possibly related to the drug.
Peptide
Semaglutide
Outcome
Not applicableDeaths
Study
n = 362
Outcome group
Mortality · Whole body
Studied dose
0.5 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
four (1%) in the 0·5 mg semaglutide group (three cardiovascular deaths, one pancreatic carcinoma, which was assessed as being possibly related to study medication)
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea.
Summary · context
We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose…
Report a problemFND-2834411211
12HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, nausea was the most frequent adverse event with semaglutide 0·5 mg, reported by 21%.
In plain wordsIn adults with type 2 diabetes, nausea was the most common side effect of semaglutide 0·5 mg, reported by about one in five people.
Peptide
Semaglutide
Outcome
Direction not reportedNausea
Study
n = 362
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
0.5 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
The most frequently reported adverse events were nausea with semaglutide, reported in 77 (21%) patients with 0·5 mg and in 80 (22%) with 1·0 mg, and nasopharyngitis reported in 44 (12%) patients with insulin glargine.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea.
Summary · context
We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose…
Report a problemFND-2834411212
13HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, nausea was the most frequent adverse event with semaglutide 1·0 mg, reported by 22%.
In plain wordsIn adults with type 2 diabetes, nausea was the most common side effect of semaglutide 1·0 mg, reported by about one in five people.
Peptide
Semaglutide
Outcome
Direction not reportedNausea
Study
n = 360
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
1.0 mg once weekly · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
The most frequently reported adverse events were nausea with semaglutide, reported in 77 (21%) patients with 0·5 mg and in 80 (22%) with 1·0 mg, and nasopharyngitis reported in 44 (12%) patients with insulin glargine.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea.
Summary · context
We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose…
Report a problemFND-2834411213

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 postedNCT02128932

Efficacy and Safety of Semaglutide Once Weekly Versus Insulin Glargine Once Daily as add-on to Metformin With or Without Sulphonylurea in Insulin-naïve Subjects With Type 2 Diabetes

Novo Nordisk A/Sn = 1,0894 Aug 2014 to 3 Sept 2015

Diabetes · Diabetes Mellitus, Type 2

Trial page ClinicalTrials.govUpdated 13 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

Subjects

Terms as the source lists them.

Publication types

MeSH terms

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