Sema research.

Sema is a 31-residue analogue of the endogenous incretin GLP-1(7–37) engineered by Novo Nordisk under the development code NN9535. Since the initial discovery disclosure by Lau and colleagues in 2015, the peptide has become the most extensively published selective GLP-1 receptor agonist in the modern incretin literature (Knudsen & Lau, 2019).

The research landscape around Sema sits across four strata: (i) discovery and medicinal-chemistry disclosures characterising the peptide backbone, (ii) preclinical pharmacokinetic and metabolic studies, (iii) the Phase 3 SUSTAIN programme in type-2 diabetes research populations, and (iv) the Phase 3 STEP programme in overweight and obesity research populations. This page is the laboratory research reference — receptor-level pharmacology lives on the Sema mechanism of action page, and a dedicated clinical-trial deep-dive will follow in a later campaign.

Novo Nordisk's medicinal-chemistry programme built Sema from the human GLP-1(7–37) backbone by introducing an α-aminoisobutyric acid at position 8 to resist DPP-4 cleavage and attaching a C18 fatty-diacid to Lys26 via a γ-glutamate–2×OEG spacer to enable reversible albumin binding (Lau et al., 2015). The combined design pushed the circulating half-life into the range required for once-weekly dosing.

Knudsen & Lau (2019) reviewed the parallel discovery lineage of liraglutide and Sema, framing the peptide as a rational successor within Novo Nordisk's long-running GLP-1 receptor agonist portfolio. For a compound-level narrative, see the cornerstone What is Sema? guide.

NN9535 is the Novo Nordisk development code for Sema and remains the primary identifier used across the peptide's early Phase 1 pharmacokinetic reports and internal discovery documentation. Preclinical characterisation under this code established the sub-nanomolar potency at GLP-1R, the extended albumin-bound half-life and the absence of meaningful GIP or glucagon receptor engagement (Lau et al., 2015; Knudsen & Lau, 2019).

When cross-referencing older pharmacology literature, laboratories should treat “NN9535” and “Sema” as synonymous — both refer to the same 31-residue AIB-8 lipidated peptide backbone.

In in-vitro research, Sema is the reference selective GLP-1 receptor agonist and is widely used as the comparator anchor peptide across the incretin class. Common experimental applications include:

• Reference-agonist role in functional cAMP accumulation assays on GLP-1R-expressing HEK293 or CHO reporter lines.
• β-arrestin recruitment and receptor-trafficking studies alongside native GLP-1(7–37).
• Comparator peptide in GIP + GLP-1 dual-agonist (Tirz) and GLP-1 + GIP + glucagon triple-agonist (RT3) receptor panels.
• Structure–activity relationship studies of lipidated GLP-1 analogues and albumin-binding tail chemistry.
• Peptide-stability, freeze–thaw and formulation reference studies for long-acting incretin backbones.

Every one of these applications depends on a well-characterised research-grade peptide with a traceable batch-specific COA — the requirement documented in the BuyRetaUK laboratory quality framework.

The Sema literature has expanded rapidly since the 2015 discovery disclosure and now spans several hundred peer-reviewed publications across discovery pharmacology, preclinical models, and the SUSTAIN and STEP Phase 3 programmes. The most widely cited foundational references include:

• Lau et al., 2015 (J. Med. Chem.): discovery and design rationale for the once-weekly GLP-1 analogue.
• Knudsen & Lau, 2019 (Frontiers in Endocrinology): discovery-lineage review of liraglutide and Sema.
• Sorli et al., 2017 (Lancet Diabetes & Endocrinology): SUSTAIN 1 read-out.
• Marso et al., 2016 (NEJM): SUSTAIN-6 cardiovascular-outcomes trial.
• Wilding et al., 2021 (NEJM): STEP 1 body-weight trial.
• Rubino et al., 2021 (JAMA): STEP 4 weight-loss maintenance trial.
• Nauck et al., 2021 (Molecular Metabolism): state-of-the-art review of the GLP-1 receptor agonist class.

STEP (Sema Treatment Effect in People with obesity) is Novo Nordisk's Phase 3 clinical trial programme evaluating once-weekly Sema in overweight and obesity research populations. STEP 1 (Wilding et al., 2021) is the flagship read-out and is the most-cited body-weight trial in the modern GLP-1 receptor agonist literature; STEP 4 (Rubino et al., 2021) characterises maintenance after initial run-in.

For laboratory supply, STEP is relevant only as the citation framework for selective GLP-1R obesity-research literature; a dedicated STEP / SUSTAIN clinical-trial deep-dive is planned as its own page and is not duplicated here.

SUSTAIN is the parallel Novo Nordisk Phase 3 programme in type-2 diabetes research populations, running from SUSTAIN 1 monotherapy (Sorli et al., 2017) through the cardiovascular-outcomes trial SUSTAIN-6 (Marso et al., 2016) and across multiple active-comparator studies. Together the SUSTAIN read-outs form the primary published evidence base for selective GLP-1 receptor agonism in T2D research.

As with STEP, SUSTAIN is cited here purely as the reference framework for the class; the receptor-level mechanism sits on the Sema mechanism of action page.

Sema sits at the reference position within incretin pharmacology because it is the most extensively published selective GLP-1 receptor agonist in the field. That role makes it the natural comparator anchor for every dual (Tirz) and triple (RT3) agonist assay panel and the default reference peptide in signalling-bias and receptor-trafficking studies.

• Reference selective GLP-1R agonist for receptor pharmacology and assay development.
• Comparator anchor across single, dual and triple incretin agonist studies.
• Model long-acting lipidated GLP-1 analogue for pharmacokinetic and formulation work.
• Reproducibility benchmark for cAMP potency and β-arrestin recruitment protocols on GLP-1R.

BuyRetaUK releases Sema against the peptide-specific quality attributes described in USP General Chapter <1503>. No vial enters inventory without a formal release specification and a batch-specific Certificate of Analysis. Full detail on supplier qualification, retained-sample and stability policies lives on the laboratory quality page — this section summarises the essentials relevant to research use.

• Purity: ≥99% by HPLC-UV area-percent.
• Identity: Mass spectrometry confirmation against the theoretical monoisotopic mass of the 31-residue AIB-8 lipidated backbone.
• Appearance: White to off-white lyophilised cake or powder.
• Traceability: Vial batch number matches the published COA record exactly.

Every research-grade Sema batch passes independent HPLC-UV purity confirmation, mass-spectrometry identity verification and visual appearance inspection before release. Batch documentation is published in the public verification library so any laboratory can cross-reference the vial in front of them. For commercial framing, see the Sema UK hub.

A Certificate of Analysis (COA) is the primary quality record for a peptide lot. For Sema it captures compound identity, batch number, manufacture date, purity method and result, mass-spectrometry identity confirmation, appearance and — where determined — endotoxin and moisture data.

See the full Certificate of Analysis guide for a section-by-section walkthrough, or open the verification library to cross-reference a specific batch.

Lyophilised Sema vials are stored at 2–8 °C, protected from light. Working stocks reconstituted with bacteriostatic water are held refrigerated and used within 30 days, avoiding repeated freeze-thaw cycles. Full handling detail lives in the shared storage & reconstitution guide — kept concise here to avoid duplication.

Use the reconstitution calculator to convert vial strength and target concentration into a diluent volume.