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Semaglutide clinical trials.

A UK laboratory reference summarising the published clinical trial evidence for semaglutide (NN9535) — the SUSTAIN Phase 3 programme in type-2 diabetes research and the STEP Phase 3 programme in overweight and obesity research, framed as a scientific literature overview. For in-vitro research context only; no medical guidance.

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BuyRetaUK Semaglutide (NN9535) research peptide vial — clinical evidence reference page

Published: July 2026
Last reviewed: July 2026
Next review: December 2026
Version: v1.1
Reading time: 10 min read
Reviewed by: BuyRetaUK Scientific Review Team
Editorial team: BuyRetaUK Editorial Team
Review status: Scientific review complete

Quick summary

Semaglutide clinical trials are the peer-reviewed Phase 1 – Phase 3 studies of NN9535, the once-weekly selective GLP-1 receptor agonist peptide originated by Novo Nordisk. The evidence base is anchored by the SUSTAIN programme in type-2 diabetes research and the STEP programme in overweight and obesity research, supported by the SELECT cardiovascular outcome trial and earlier pharmacokinetic and receptor-pharmacology literature. This page summarises the published record as an evidence reference; it does not provide medical advice or treatment guidance.

Quick answer

In short.

Key facts

At a glance.

Research compound: Semaglutide (NN9535)
Class: Selective GLP-1 receptor agonist peptide
First discovery disclosure: Lau et al., 2015 (J. Med. Chem.)
Phase 3 in T2D research: SUSTAIN programme (SUSTAIN 1 – SUSTAIN 10)
Phase 3 in obesity research: STEP programme (STEP 1 – STEP 8)
Cardiovascular outcomes: SUSTAIN-6 (Marso 2016) · SELECT (Lincoff 2023)
Oral formulation programme: PIONEER trials (oral semaglutide)
Comparators cited: Placebo · sitagliptin · exenatide · liraglutide · dulaglutide · insulin glargine · canagliflozin
Publication venues: NEJM · The Lancet · JAMA · Lancet Diabetes & Endocrinology
Page scope: Published evidence summary — no medical guidance

Definitions

Key terms.

Clinical trial: A structured research study in human volunteers, conducted under a pre-specified protocol to evaluate the pharmacology, safety or efficacy of an investigational agent.
Phase 1: First-in-human studies focused on safety, tolerability and pharmacokinetics in small volunteer cohorts.
Phase 2: Dose-ranging and early efficacy studies in the target research population.
Phase 3: Large, randomised, controlled studies designed to characterise efficacy and safety versus established comparators.
SUSTAIN: Novo Nordisk's Phase 3 clinical trial programme evaluating once-weekly semaglutide in type-2 diabetes research populations (SUSTAIN 1 through SUSTAIN 10).
STEP: Novo Nordisk's Phase 3 clinical trial programme evaluating once-weekly semaglutide in overweight and obesity research populations (STEP 1 through STEP 8).
SELECT: The dedicated cardiovascular outcome trial of once-weekly semaglutide in overweight or obesity research populations with established cardiovascular disease (Lincoff 2023).
PIONEER: Novo Nordisk's clinical programme evaluating an oral formulation of semaglutide in type-2 diabetes research populations.

Overview

Overview of the published evidence.

The semaglutide evidence base has grown from a single 2015 discovery disclosure into one of the most extensively published incretin literatures in modern metabolic science. Foundational medicinal-chemistry work (Lau 2015) framed the peptide, the SUSTAIN programme generated the pivotal Phase 3 dataset in type-2 diabetes research, the STEP programme extended the dataset into overweight and obesity research at the 2.4 mg dose, and the SELECT outcome trial (Lincoff 2023) added the dedicated cardiovascular endpoint dataset in obesity research populations without diabetes.

This page summarises the published evidence at the programme level. Receptor-level pharmacology lives on the Semaglutide mechanism of action page, and the broader laboratory research context sits on Semaglutide research. This page does not provide medical or treatment guidance.

Development timeline

Publication and development timeline.

2015: Lau et al. disclose the discovery and structure–activity design of the once-weekly GLP-1 analogue semaglutide (J. Med. Chem.).
2016: SUSTAIN-6 cardiovascular outcome trial published in NEJM (Marso et al.).
2017: First SUSTAIN Phase 3 read-outs (SUSTAIN 1, 2 and 4) published in The Lancet Diabetes & Endocrinology.
2018: SUSTAIN 3 (Diabetes Care) and SUSTAIN 7 head-to-head vs dulaglutide (Lancet D&E) round out the initial T2D dataset.
2021: STEP 1 (NEJM), STEP 2 (Lancet) and STEP 4 (JAMA) establish once-weekly semaglutide 2.4 mg as the reference obesity-research dose.
2023: SELECT cardiovascular outcome trial in overweight/obesity without diabetes published in NEJM (Lincoff et al.).

SUSTAIN programme

SUSTAIN programme overview.

SUSTAIN is Novo Nordisk's Phase 3 clinical trial programme evaluating once-weekly semaglutide in type-2 diabetes research populations. It comprises ten pivotal trials that pair semaglutide against a broad set of active and placebo comparators — sitagliptin, exenatide extended-release, insulin glargine, dulaglutide and canagliflozin among them — so the selective GLP-1 receptor agonist mechanism can be positioned against the major reference classes.

SUSTAIN-6 is the dedicated cardiovascular outcome study within the programme and is cited throughout the incretin literature as the primary CV safety trial for the T2D indication (Marso 2016). SUSTAIN 7 provides the direct head-to-head read-out against once-weekly dulaglutide within the GLP-1 receptor agonist class (Pratley 2018).

Trial	Research population	Comparator	Primary endpoint	Reference
SUSTAIN 1	Drug-naïve T2D research	Placebo	HbA1c change from baseline	Sorli 2017 (Lancet D&E)
SUSTAIN 2	T2D on metformin ± TZD	Sitagliptin	HbA1c change from baseline	Ahrén 2017 (Lancet D&E)
SUSTAIN 3	T2D on OADs	Exenatide ER	HbA1c change from baseline	Ahmann 2018 (Diabetes Care)
SUSTAIN 4	Insulin-naïve T2D on metformin ± SU	Insulin glargine	HbA1c change from baseline	Aroda 2017 (Lancet D&E)
SUSTAIN-6	T2D with high CV risk	Placebo (CV outcomes)	MACE (CV outcome trial)	Marso 2016 (NEJM)
SUSTAIN 7	T2D on metformin	Dulaglutide	HbA1c change from baseline	Pratley 2018 (Lancet D&E)

STEP programme

STEP programme overview.

STEP is the parallel Phase 3 clinical trial programme evaluating once-weekly semaglutide 2.4 mg in overweight and obesity research populations. It spans STEP 1 through STEP 8 and characterises the peptide across different body-weight cohorts, coexisting T2D status, background lifestyle interventions and weight-maintenance study designs.

For laboratory-supply purposes STEP is referenced as the pivotal citation set that anchors selective GLP-1 receptor agonist obesity-research reviews. Receptor-level interpretation of the STEP read-outs belongs on the mechanism of action page.

Trial	Research population	Comparator	Primary endpoint	Reference
STEP 1	Adults with overweight/obesity, without T2D	Placebo	% body-weight change	Wilding 2021 (NEJM)
STEP 2	Adults with overweight/obesity and T2D	Placebo & 1.0 mg semaglutide	% body-weight change	Davies 2021 (Lancet)
STEP 4	Weight-maintenance after 20-week lead-in	Placebo (continuation vs switch)	% body-weight change from wk 20	Rubino 2021 (JAMA)

Scientific themes

Key scientific themes across the trial literature.

Selective GLP-1 receptor agonism at scale: the SUSTAIN and STEP programmes together form the largest randomised dataset for a single-incretin GLP-1 analogue in the field.
Cardiovascular endpoint characterisation: SUSTAIN-6 (T2D) and SELECT (obesity without diabetes) provide dedicated CV outcome data for the peptide.
Direct within-class comparison: SUSTAIN 7 head-to-head against dulaglutide anchors the intra-GLP-1RA comparator literature.
Dose-escalation architecture: STEP trials employ a stepwise titration schedule to 2.4 mg, informing how the compound is referenced in laboratory PK and receptor-occupancy modelling.
Oral-formulation extension: the PIONEER programme extended the semaglutide evidence base to an oral formulation, complementing the once-weekly subcutaneous dataset.

Evidence quality

Evidence quality and interpretation.

From a research-literature perspective, the semaglutide Phase 3 dataset scores highly on core internal-validity markers: pre-registered protocols, randomisation, active comparators, large sample sizes, and publication in top-quartile peer-reviewed journals. The regulatory-grade dataset generated by SUSTAIN, STEP and SELECT is routinely integrated into systematic reviews and meta-analyses of the GLP-1 receptor agonist class.

Interpretation for laboratory purposes should remain focused on what the trials characterise — the pharmacology, PK behaviour and comparator profile of NN9535 — rather than on downstream clinical decisions, which sit outside the scope of this reference.

Limitations

Research limitations of the current evidence base.

The bulk of the Phase 3 dataset is generated by a single sponsor programme.
Background regimens across SUSTAIN arms are heterogeneous, which complicates cross-trial pooling.
Follow-up in several STEP trials is short relative to the lifetime course of metabolic disease research.
Head-to-head data against the dual and triple agonist classes remain limited to SURPASS-2 (indirect at the programme level).
Long-term real-world evidence at the 2.4 mg obesity-research dose is still maturing.

Laboratory relevance

Laboratory relevance of the trial literature.

Within an in-vitro laboratory context, the SUSTAIN and STEP programmes provide the citation framework that justifies semaglutide's role as the reference selective GLP-1 receptor agonist comparator. Typical uses of the trial literature in laboratory workflows include:

Framing NN9535 as the reference peptide in receptor-pharmacology reviews and grant applications.
Sourcing published PK parameters when designing stability, degradation or albumin-binding assays.
Citing SUSTAIN 7 and SURPASS-2 read-outs when semaglutide is used as a comparator alongside dulaglutide or tirzepatide.
Establishing dose-escalation rationale for cross-species preclinical model design against a published titration schedule.

Every research-grade semaglutide batch is released against the peptide-specific quality attributes summarised on laboratory quality and documented by a batch-specific COA — see the Certificate of Analysis guide and the verification library.

Laboratory quality

Quality standards.

HPLC Testing

Reverse-phase HPLC quantifies purity as a percentage of total peak area. Release specification: ≥99%.

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Learn more →Storage Standards

Lyophilised at 2–8°C protected from light. Reconstituted stability ~30 days at 2–8°C.

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Frequently asked questions

FAQs.

What are the semaglutide clinical trials?[+]

The semaglutide clinical trials are the Phase 1 – Phase 3 studies of NN9535 published across the peer-reviewed literature. The Phase 3 programme is organised into two primary pillars: SUSTAIN in type-2 diabetes research populations and STEP in overweight and obesity research populations, complemented by the SELECT cardiovascular outcome trial and the PIONEER programme evaluating an oral formulation.

What is the SUSTAIN programme?[+]

SUSTAIN is Novo Nordisk's Phase 3 clinical trial programme in type-2 diabetes research populations. It spans SUSTAIN 1 through SUSTAIN 10 and evaluates once-weekly semaglutide against a range of comparators including placebo, sitagliptin, exenatide extended-release, insulin glargine, dulaglutide and canagliflozin. SUSTAIN-6 also served as the cardiovascular safety trial for the diabetes indication.

What is the STEP programme?[+]

STEP is Novo Nordisk's Phase 3 clinical trial programme in overweight and obesity research populations. It spans STEP 1 through STEP 8 and characterises once-weekly semaglutide 2.4 mg across different body-weight research cohorts, background lifestyle interventions and comparator arms.

Where are the semaglutide trial results published?[+]

Primary read-outs have been published in high-impact peer-reviewed journals including the New England Journal of Medicine, The Lancet, JAMA and The Lancet Diabetes & Endocrinology, with pharmacokinetic and pharmacology papers in the Journal of Medicinal Chemistry, Molecular Metabolism and Frontiers in Endocrinology.

How does the semaglutide evidence base compare with tirzepatide?[+]

The direct head-to-head data point is SUSTAIN-7 (semaglutide vs dulaglutide) at the GLP-1 class level, and SURPASS-2 (tirzepatide vs semaglutide) at the dual-vs-single-agonist level. Beyond these specific trials, comparisons between the SUSTAIN/STEP and SURPASS/SURMOUNT programmes are drawn indirectly at the literature level rather than as pooled head-to-head analyses.

Does regulatory approval mean the trials support human use in the UK?[+]

Semaglutide has received regulatory authorisations in multiple jurisdictions under its branded forms. BuyRetaUK supplies research-grade semaglutide strictly for in-vitro laboratory investigation. This page summarises the published evidence and does not provide medical, prescribing or treatment guidance.

What are the main limitations of the semaglutide evidence base?[+]

Key limitations include the concentration of trials within a single sponsor's programme, heterogeneity of background regimens across SUSTAIN, the relatively short follow-up of several STEP trials compared with lifetime metabolic disease trajectories, and the still-maturing long-term real-world dataset for the 2.4 mg obesity dose.

Does this page provide medical or treatment advice?[+]

No. This page is an educational summary of published scientific evidence for laboratory-research context. It is not medical guidance and does not discuss patient decision-making.

References

Scientific sources & further reading.

[1]Lau J. et al. (2015) Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide. Journal of Medicinal Chemistry, 58(18): 7370–7380 DOI: 10.1021/acs.jmedchem.5b00726DOI →
[2]Sorli C. et al. (2017) Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. The Lancet Diabetes & Endocrinology, 5(4): 251–260 DOI: 10.1016/S2213-8587(17)30013-XDOI →
[3]Ahrén B. et al. (2017) Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2). The Lancet Diabetes & Endocrinology, 5(5): 341–354 DOI: 10.1016/S2213-8587(17)30092-XDOI →
[4]Ahmann A.J. et al. (2018) Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3). Diabetes Care, 41(2): 258–266 DOI: 10.2337/dc17-0417DOI →
[5]Aroda V.R. et al. (2017) 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). The Lancet Diabetes & Endocrinology, 5(5): 355–366 DOI: 10.1016/S2213-8587(17)30085-2DOI →
[6]Marso S.P. et al. (2016) Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6). New England Journal of Medicine, 375(19): 1834–1844 DOI: 10.1056/NEJMoa1607141DOI →
[7]Pratley R.E. et al. (2018) Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. The Lancet Diabetes & Endocrinology, 6(4): 275–286 DOI: 10.1016/S2213-8587(18)30024-XDOI →
[8]Wilding J.P.H. et al. (2021) Once-weekly semaglutide in adults with overweight or obesity (STEP 1). New England Journal of Medicine, 384(11): 989–1002 DOI: 10.1056/NEJMoa2032183DOI →
[9]Davies M. et al. (2021) Semaglutide 2.4 mg once a week in adults with overweight or obesity and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. The Lancet, 397(10278): 971–984 DOI: 10.1016/S0140-6736(21)00213-0DOI →
[10]Rubino D. et al. (2021) Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity (STEP 4). JAMA, 325(14): 1414–1425 DOI: 10.1001/jama.2021.3224DOI →
[11]Lincoff A.M. et al. (2023) Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). New England Journal of Medicine, 389(24): 2221–2232 DOI: 10.1056/NEJMoa2307563DOI →
[12]Nauck M.A., Quast D.R., Wefers J., Meier J.J. (2021) GLP-1 receptor agonists in the treatment of type 2 diabetes — state-of-the-art. Molecular Metabolism, 46: 101102 DOI: 10.1016/j.molmet.2020.101102DOI →
[13]Drucker D.J. (2018) Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metabolism, 27(4): 740–756 DOI: 10.1016/j.cmet.2018.03.001DOI →

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Semaglutide
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ResearchSemaglutide Research

Laboratory-oriented overview of the research landscape and evidence base.

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Where this sits in the Semaglutide cluster.

Knowledge journey

Semaglutide clinical trials.

Quick summary

In short.

At a glance.

Key terms.

Overview of the published evidence.

Publication and development timeline.

SUSTAIN programme overview.

STEP programme overview.

Key scientific themes across the trial literature.

Evidence quality and interpretation.

Research limitations of the current evidence base.

Laboratory relevance of the trial literature.

Quality standards.

FAQs.

Scientific sources & further reading.

How this content is produced.

Your research-to-checkout journey.

How to research this topic.

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