Evidence map›GLP-1 receptor agonists × glycemic control›PMID 29688502›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2018

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

Registry-linked trialOpen access · hybridFull text readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2018. The graph read 6 numbers from its abstract, feeding 3 cells of the map: it supports the treatment in 2, finds no clear difference in 1. It reports registered trial NCT02305381. Cited by 182 papers, 24 of them syntheses that pooled it.

6numbers the graph read from it
3cells of the map it votes in
182citing papers in PubMed, 24 pooled it
20.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

Ratios

← favours the treatmentfavours the comparator →
241 · no effect
Severe or blood glucose-confirmed hypoglycemic episodessemaglutide 1.0 mg vs placebono clear difference · t2dfeeds one cell of the map
IRR 2.410.84 to 6.96nonsignificant
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).

The authors add: both P = nonsignificant

FeedsGLP-1 receptor agonists×hypoglycaemia
Severe or blood glucose-confirmed hypoglycemic episodessemaglutide 0.5 mg vs placebono clear difference · t2dfeeds one cell of the map
IRR 2.080.67 to 6.51nonsignificant
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).

The authors add: both P = nonsignificant

FeedsGLP-1 receptor agonists×hypoglycaemia

Differences

← favours the treatmentfavours the comparator →
-6.080 · no effect
HbA1c reduction from baseline to week 30semaglutide 0.5 mg vs placebofavours the treatment · t2dfeeds one cell of the map
Δ -1.35-1.61 to -1.10< 0.0001
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].
FeedsGLP-1 receptor agonists×glycemic control
Mean body weight decrease from baseline to end of treatmentsemaglutide 1.0 mg vs placebofavours the treatment · t2dfeeds one cell of the map
Δ -5.06-6.08 to -4.04< 0.0001
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).
FeedsGLP-1 receptor agonists×body weight & composition
Mean body weight decrease from baseline to end of treatmentsemaglutide 0.5 mg vs placebofavours the treatment · t2dfeeds one cell of the map
Δ -2.31-3.33 to -1.29< 0.0001
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).
FeedsGLP-1 receptor agonists×body weight & composition
HbA1c reduction from baseline to week 30semaglutide 1.0 mg vs placebofavours the treatment · t2dfeeds one cell of the map
Δ -1.75-2.01 to -1.50< 0.0001
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].
FeedsGLP-1 receptor agonists×glycemic control

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

GLP-1 receptor agonists×glycemic control

SupportsOpen on the map →What to test next →

40 readable studies in this cell: 96 favour the treatment, 17 find no difference, 10 favour the comparator.

Belief with this paper
0.91replicated · 68 families support, 7 contradict · against placebo
Without it
0.91This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper’s trial, registry resultNCT02305381 · 397 enrolled · 2014
Δ -1.75-2.01 to -1.50
This paper · 2018
Δ -1.35-1.61 to -1.10
NCT017204463,297 enrolled · 2013
Δ -0.66-0.80 to -0.52
NCT036893742,274 enrolled · 2018
Δ -0.29-0.38 to -0.20
NCT039879191,879 enrolled · 2019
Δ -0.51-0.64 to -0.38
NCT026078651,864 enrolled · 2016
Δ -0.50-0.60 to -0.40
NCT013360231,663 enrolled · 2011
Treatment contrast -0.64-0.75 to -0.53
NCT040178321,441 enrolled · 2019
Δ -0.20-0.30 to -0.10
NCT018365231,398 enrolled · 2013
Δ -0.20-0.32 to -0.07
NCT019301881,231 enrolled · 2013
Δ -1.06-1.21 to -0.91
NCT007344741,202 enrolled · 2008
Δ -0.71-0.87 to -0.55
NCT020581471,170 enrolled · 2014
Δ -0.29-0.38 to -0.19
NCT003184611,091 enrolled · 2006
Δ -1.09-1.30 to -0.88
NCT021289321,089 enrolled · 2014
Δ -0.81-0.96 to -0.67

GLP-1 receptor agonists×body weight & composition

SupportsOpen on the map →What to test next →

40 readable studies in this cell: 83 favour the treatment, 15 find no difference, 11 favour the comparator.

Belief with this paper
0.90replicated · 64 families support, 7 contradict · against placebo
Without it
0.90This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2018
Δ -5.06-6.08 to -4.04
NCT012722193,731 enrolled · 2011
Δ -5.39-5.82 to -4.95
Coadministered Cagrilintide and Semaglutide in Adults with Overweight …PMID 40544433 · 3,400 enrolled · 2022
Δ -17.3-18.1 to -16.6
NCT017204463,297 enrolled · 2013
Δ -2.95-3.47 to -2.44
NCT035489351,961 enrolled · 2018
Δ -12.4-13.4 to -11.5
NCT039879191,879 enrolled · 2019
Δ -1.70-2.60 to -0.70
NCT026078651,864 enrolled · 2016
Δ -2.50-3.00 to -2.00
NCT056467061,407 enrolled · 2023
Δ -14.8-16.2 to -13.4
NCT018365231,398 enrolled · 2013
Δ -4.90-5.65 to -4.16
NCT035527571,210 enrolled · 2018
Δ -6.21-7.28 to -5.15
NCT007344741,202 enrolled · 2008
Δ -1.50-2.08 to -0.92
Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type…PMID 40544432 · 1,200 enrolled · 2023
Δ -10.4-11.2 to -9.50
NCT020581471,170 enrolled · 2014
Δ 14.38.37 to 20.3

GLP-1 receptor agonists×hypoglycaemia

InconclusiveOpen on the map →What to test next →

11 readable studies in this cell: 2 favour the treatment, 3 find no difference, 6 favour the comparator.

Belief with this paper
0.50contested · 3 families support, 1 contradict · against placebo
Without it
0.50This paper does not move the number.
← favours the treatmentfavours the comparator →
1 · no effect
This paper · 2018
IRR 2.410.84 to 6.96
NCT018365231,398 enrolled · 2013
IRR 1.311.07 to 1.59
NCT02607306819 enrolled · 2015
Treatment contrast 0.480.35 to 0.68
NCT00393718400 enrolled · 2006
IRR 0.200.12 to 0.35
NCT02152371300 enrolled · 2014
OR 4.172.32 to 7.47
NCT04591626291 enrolled · 2020
OR 4.582.64 to 7.95
NCT05564039282 enrolled · 2022
OR 20.48.40 to 49.8
NCT01620489279 enrolled · 2012
OR 3.942.12 to 7.30
4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02305381 phase3completed

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

Ran2014Enrolled397Registered outcomes8Posted comparisons2ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsPlacebo, semaglutide
PMID 29862621PMID 30615985PMID 30865526PMID 29687620PMID 29766634other papers from this trial
Open the trial in the graph
5 · Its place in the literature

Who cites it

182 citing papers in PubMed, 24 syntheses or guidelines pooled it, 374 citations in OpenAlex.

  1. Pooled it
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  4. Meta-analysis of the Effect of Semaglutide on Blood Pressure in Obese Populations.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2025 · on this map
    Pooled it
  5. Pooled it
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  8. Pooled it
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  13. Guideline
  14. Pooled it
  15. Clinical Pharmacokinetics of Semaglutide: A Systematic Review.Drug design, development and therapy · 2024
    Pooled it
  16. Pooled it
  17. Guideline
  18. Pooled it
  19. Pooled it
  20. Pooled it

122 more citing papers are in PubMed but not listed here.

6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

10 authors at 6 institutions in 4 countries.

Helena W RodbardEndocrine and Metabolic Consultants, Rockville, Maryland.
Ildiko LingvayDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
John ReedEndocrine Research Solutions, Inc., Roswell, Georgia.
Raymond de la RosaFour Rivers Clinical Research, Paducah, Kentucky.
Ludger RoseInstitute of Diabetes Research, Münster, Germany.
Danny SugimotoCedar-Crosse Research Center, Chicago, Illinois.
Eiichi ArakiDepartment of Metabolic Medicine, Kumamoto University, Kumamoto, Japan.
Pei-Ling ChuNovo Nordisk Inc., Plainsboro, New Jersey.
Nelun WijayasingheNovo Nordisk A/S, Søborg, Denmark.
Paul NorwoodUniversity of California at San Francisco, Fresno, California.
California State University, Fresno · USInstitute of Diabetes ResearchKumamoto University · JPNovo Nordisk (Denmark) · DKNovo Nordisk (United States) · USThe University of Texas Southwestern Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

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.

Indexed as

AdultAgedAged, 80 and overBlood GlucoseDiabetes Mellitus, Type 2Double-Blind MethodDrug Therapy, CombinationFemaleGlucagon-Like PeptidesGlycated HemoglobinHumansHypoglycemic AgentsInsulinMaleMiddle AgedSemaglutideBlood GlucoseGlucagon-Like PeptidesGlycated Hemoglobinhemoglobin A1c protein, humanHypoglycemic AgentsInsulinSemaglutide

Identifiers

PMID29688502
PMCPMC5991220
OpenAlexW2801715295

What Socratic holds

Textfull text, public
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.