Evidence map›Paper›PMID 29748996›Full record

ArticleDiabetes, obesity & metabolism2018

Exposure-response analysis for evaluation of semaglutide dose levels in type 2 diabetes.

Kristin C C Petri, Steen H Ingwersen, Anne Flint, Jeppe Zacho, Rune V Overgaard

4 registry-linked trialsAbstract readEvaluation Study
In one paragraph

Article in Diabetes, obesity & metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01885208. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · 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.

NCT01885208 phase3completed

Efficacy and Safety of Semaglutide Once-weekly Versus Exenatide ER 2.0 mg Once-weekly as add-on to 1-2 Oral Antidiabetic Drugs (OADs) in Subjects With Type 2 Diabetes (SUSTAIN™ 3 - vs. QW GLP-1)

Ran2013Enrolled813Registered outcomes6Posted comparisons2ConditionsDiabetes, Diabetes Mellitus, Type 2Armsexenatide, semaglutide
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NCT01930188 phase3completed

Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin and/or TZD in Subjects With Type 2 Diabetes (SUSTAIN™ 2 - vs. DPP-4 Inhibitor)

Ran2013Enrolled1,231Registered outcomes6Posted comparisons2ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsPlacebo, semaglutide, Sitagliptin
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NCT02054897 phase3completed

Efficacy and Safety of Semaglutide Once-weekly Versus Placebo in Drug-naïve Subjects With Type 2 Diabetes

Ran2014Enrolled388Registered outcomes6Posted comparisons2ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsPlacebo, semaglutide
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NCT02207374 phase3completed

Safety and Efficacy of Semaglutide Once Weekly in Monotherapy or in Combination With One OAD in Japanese Subjects With Type 2 Diabetes Who Are Insufficiently Controlled on Diet/Exercise Therapy or OAD Monotherapy

Ran2014Enrolled601Registered outcomes3Posted comparisons0ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsDPP-4 inhibitor, semaglutide
PMID 29322610PMID 29907893other papers from this trial
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3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  11. Dose-Response and Clinical Equivalence of Semaglutide and Tirzepatide for Weight Loss in Type 2 Diabetes: A Model-Based Analysis.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026
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4 · The record

Corrections and comments

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

5 · Who and what money

Authors and funding

5 authors.

Kristin C C PetriDepartment of Quantitative Clinical Pharmacology, Novo Nordisk A/S, Søborg, Denmark.ORCID http://orcid.org/0000-0001-8417-8575
Steen H IngwersenDepartment of Quantitative Clinical Pharmacology, Novo Nordisk A/S, Søborg, Denmark.
Anne FlintDepartment of Clinical Pharmacology, Novo Nordisk A/S, Søborg, Denmark.
Jeppe ZachoDepartment of Semaglutide Medical and Science, Global Development, Novo Nordisk A/S, Søborg, Denmark.
Rune V OvergaardDepartment of Quantitative Clinical Pharmacology, Novo Nordisk A/S, Søborg, Denmark.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsTo evaluate dose levels for semaglutide, a glucagon-like peptide-1 analogue approved for the treatment of type 2 diabetes, by examining the effects of demographic factors on efficacy and safety in an exposure-response analysis.

methodsWe analysed data from 1552 adults from four randomized phase III trials of 30 to 56 weeks' duration, investigating once-weekly semaglutide doses 0.5 and 1.0 mg. Exposure-response relationships were investigated using graphical and model-based techniques to assess the two dose levels and subgroups with the highest and lowest exposure and response.

resultsThe population had the following demographic characteristics: baseline mean age between 53.2 and 58.4 years, glycated haemoglobin (HbA1c) between 64 and 67 mmol/mol (8.0% and 8.3%), body weight between 71.3 and 96.2 kg, and diabetes duration between 4.2 and 8.9 years. Exposure-response analysis showed a clear HbA1c and weight reduction across exposures after 30 weeks, irrespective of baseline values. The exposure-response for HbA1c was influenced by baseline HbA1c, and body weight exposure-response was influenced by sex, with limited impact of other factors. Analyses for relevant subgroups of baseline body weight, baseline HbA1c and sex indicated clinically relevant additional benefits with regard to HbA1c and weight with 1.0 vs 0.5 mg semaglutide. The proportion of participants reporting gastrointestinal (GI) side effects increased with increasing exposure, but was counteracted by tolerance development.

conclusionsThe analysis showed that all subgroups obtained a clinically relevant benefit with semaglutide 0.5 mg and an additional benefit with semaglutide 1.0 mg. The increase in GI side effects with higher exposure was mitigated by gradually increasing the dose.

Indexed as

Blood GlucoseClinical Trials, Phase III as TopicDiabetes Mellitus, Type 2Dose-Response Relationship, DrugFemaleGlucagon-Like PeptidesGlycated HemoglobinHumansHypoglycemic AgentsMaleMiddle AgedRandomized Controlled Trials as TopicSemaglutideTreatment OutcomeWeight LossBlood GlucoseGlucagon-Like PeptidesGlycated Hemoglobinhemoglobin A1c protein, humanHypoglycemic AgentsSemaglutideGLP-1GLP-1 analoguetype 2 diabetes

Identifiers

PMID29748996
PMCPMC6099226

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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 OpenQuestion graph.