Semaglutide — identity, handling and published literature

Semaglutide is a synthetic 31-residue acylated analogue of human glucagon-like peptide-1, supplied as a lyophilised powder for reconstitution in the laboratory.

Presentation and physical properties

Semaglutide is supplied as a white to off-white lyophilised solid. It is a single-chain peptide of 31 amino acid residues built on the glucagon-like peptide-1 (7–37) backbone, carrying three structural modifications relative to the native sequence: 2-aminoisobutyric acid (Aib) replaces alanine at position 8, arginine replaces lysine at position 34, and the side-chain amine of lysine at position 26 is acylated through a γ-glutamyl and bis-(2-(2-aminoethoxy)ethoxy)acetyl (AEEA) spacer to octadecanedioic acid, an eighteen-carbon α,ω-dicarboxylic acid.

Lau and colleagues, reporting the discovery programme, describe the design logic of each substitution: the Aib residue at position 8 removes the dipeptidyl peptidase-4 cleavage site, and the fatty diacid side chain confers reversible binding to serum albumin [1]. The published human pharmacokinetic literature reports an elimination half-life in the region of one week, which is a property of the circulating molecule and carries no implication for the shelf stability of the dry solid [11, 13].

Aqueous solubility is pH-dependent, as it is for any peptide with multiple ionisable side chains, and the molecule is customarily handled in near-neutral aqueous buffer. Because the acyl chain drives association with protein and with hydrophobic surfaces, apparent losses on transfer between vessels are a recognised handling artefact rather than a degradation event.

Reconstitution arithmetic

Reconstitution is a division. For a vial containing a stated mass m of peptide and a volume V of diluent added, the resulting concentration is c = m / V. Nothing else in this section is anything other than that division carried out at three volumes.

The figures below are for a nominal 20 mg vial. On a U-100 insulin syringe one graduation mark corresponds to 0.01 mL, which is the convention used in the final column.

Three points of arithmetic hygiene apply. First, the nominal vial content is a label figure; the true peptide mass depends on the peptide content of the solid, which for an acylated peptide of this size is not the same as the gross weight, so a concentration derived from the label is nominal unless the material has been assayed. Second, adding diluent to a lyophilised cake produces a final volume slightly greater than the volume of diluent added, because the solid itself occupies volume; at these dilutions the error is small but it is systematically in one direction. Third, the 20 mg/mL row is at the concentrated end of the practical range and reconstitution at that volume is correspondingly slower.

This table converts volume to mass. It states no amount to use, and it is not capable of doing so.

Storage and stability

The dry solid is the stable form. Standard practice for lyophilised peptides is storage at −20 °C or below, desiccated and protected from light, with the vial allowed to reach room temperature before opening so that atmospheric moisture does not condense onto cold, hygroscopic material.

Once reconstituted, the peptide is in solution and the constraints change. Aqueous solutions are held refrigerated at 2–8 °C, and repeated freeze–thaw cycling is avoided; aliquoting at the point of reconstitution removes the need for it. The authorised injectable presentations of semaglutide are refrigerated products, which is consistent with the general position that the solution form is the less stable one.

Two handling-specific points follow from the acylation. The lipid side chain makes the molecule surface-active, so agitation should be by gentle inversion or swirling rather than by vortexing, and foaming indicates interfacial denaturation is being encouraged. Adsorptive loss to container surfaces is a real effect for lipidated peptides, and low-binding polypropylene is preferred to glass for dilute working solutions.

Where a bacteriostatic diluent containing benzyl alcohol is used rather than sterile water, the preservative is a property of the diluent, not of the peptide, and the choice does not alter any of the arithmetic above.

Analytical identity

Identity confirmation for semaglutide rests on orthogonal methods, because no single technique separates it from its closest relatives.

Reversed-phase high-performance liquid chromatography with ultraviolet detection at 214 nm (amide backbone) and 280 nm (tryptophan and tyrosine) gives purity as an area-percentage figure and a retention time. Retention time alone is weak evidence of identity: other long-chain acylated GLP-1 analogues elute in a similar region, and a co-eluting impurity is invisible to ultraviolet detection alone.

Electrospray ionisation mass spectrometry gives the mass and is the primary identity method. At an average mass near 4113.6 Da the molecule presents as a multiply charged envelope; the commonly observed states fall near m/z 1372 for [M+3H]³⁺, 1029 for [M+4H]⁴⁺ and 824 for [M+5H]⁵⁺. Deconvolution to a neutral mass, rather than inspection of a single charge state, is what makes the measurement diagnostic. Enzymatic digestion followed by peptide mapping localises the sequence and confirms the site of acylation, which intact mass alone does not.

Impurity classes that matter analytically for this molecule are deletion and truncated sequences arising from synthesis, des-acyl material in which the fatty-diacid side chain is absent or incomplete, oxidation at the single tryptophan residue, and diastereomeric impurities from epimerisation. Several of these are close in mass to the parent and require chromatographic resolution rather than mass alone.

One distinction is not visible to peptide mass spectrometry at all. The United States Food and Drug Administration has stated that salt forms such as semaglutide sodium and semaglutide acetate are different active ingredients from the base form contained in the approved products, that the agency does not have information on whether those salts share the chemical and pharmacological properties of the approved active ingredient, and that it is not aware of a lawful basis for their use in compounding. The peptide cation is the same in each case, so the counter-ion is determined by elemental or ion chromatographic analysis and by certificate, not by an intact-mass spectrum.

What the published literature investigated

Semaglutide has one of the largest and methodologically strongest randomised human evidence bases of any peptide in this catalogue. That is a statement about the literature. The trials below were conducted with pharmaceutical-grade, authorised-specification material under regulatory supervision, and their findings are attributed to the studies that produced them.

In vitro

Lau and colleagues reported the design and in vitro characterisation of the molecule, including receptor potency, albumin affinity and resistance to dipeptidyl peptidase-4 conferred by the Aib substitution [1]. Semaglutide has since been used as a comparator agonist in receptor pharmacology work examining G-protein versus β-arrestin signalling at the GLP-1 receptor [2] and in the in vitro characterisation of other long-acting agonists [3].

Rodent models

Gabery and colleagues reported that, in rodents, the compound accessed the brain and that its effect on body weight in those animals involved distributed neural pathways rather than a single hypothalamic site [4]. Brierley and colleagues used the compound within a broader dissection of central and peripheral GLP-1 systems in mice and reported that the two suppress eating independently [5].

In diet-induced obese and biopsy-confirmed mouse models of steatohepatitis, Møllerhøj and colleagues [6] and Niu and colleagues [7] reported effects on metabolic and hepatic endpoints, in both cases against dietary and pharmacological comparators. Chuong and colleagues reported reduced alcohol drinking and modulation of central GABA neurotransmission in rodents [8]. Li and colleagues reported attenuation of doxorubicin-induced cardiotoxicity in a rodent model, attributing the effect to BNIP3-mediated mitochondrial mechanisms [9].

Human pharmacokinetics

Marbury and colleagues reported single-dose pharmacokinetics and tolerability in participants with and without renal impairment [10]. Hall and colleagues [11] and Yang and colleagues [13] reviewed the clinical pharmacokinetic dataset; Overgaard and colleagues analysed the pharmacokinetics of the oral formulation across clinical pharmacology trials [12]. The characteristic finding across this literature is a long elimination half-life attributed to albumin binding and protease resistance.

Human trials — cardiovascular and renal endpoints

SUSTAIN-6 randomised 3,297 participants with type 2 diabetes over 104 weeks; the trial reported the composite of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke in 6.6 per cent of the semaglutide group and 8.9 per cent of the placebo group (hazard ratio 0.74, 95 per cent confidence interval 0.58 to 0.95) [14]. PIONEER 6 examined the same composite for the oral formulation [16], and SOUL subsequently randomised 9,650 participants at high cardiovascular risk over a mean of 47.5 months, reporting the composite in 12.0 per cent versus 13.8 per cent (hazard ratio 0.86, 95 per cent confidence interval 0.77 to 0.96) [22].

SELECT is the largest trial in this literature. It randomised 17,604 participants with overweight or obesity and established cardiovascular disease but without diabetes, followed for a mean of 39.8 months, and reported the primary composite in 6.5 per cent of the semaglutide group and 8.0 per cent of the placebo group (hazard ratio 0.80, 95 per cent confidence interval 0.72 to 0.90) [17]. Prespecified and secondary analyses of the same trial addressed long-term weight change [18], kidney endpoints [19] and participants with prevalent heart failure [20].

FLOW randomised 3,533 participants with type 2 diabetes and chronic kidney disease over a median 3.4 years and reported the composite major kidney disease endpoint at a hazard ratio of 0.76 (95 per cent confidence interval 0.66 to 0.88) [21]. Class-level meta-analyses of GLP-1 receptor agonist cardiovascular outcome trials, which include the semaglutide trials among others, have been published by Kristensen and colleagues [38] and by Lee and colleagues [39].

Human trials — body weight

The STEP programme is a series of randomised, placebo-controlled phase 3 trials. STEP 1 randomised 1,961 participants with overweight or obesity over 68 weeks and reported a mean change in body weight of −14.9 per cent in the semaglutide group against −2.4 per cent with placebo [23]. STEP 2 studied participants who also had type 2 diabetes [24]; STEP 3 combined the intervention with intensive behavioural therapy [25]; STEP 4 used a randomised withdrawal design to examine what happened when treatment was and was not continued [26]; STEP 5 extended follow-up to two years [27]; STEP 8 compared semaglutide against liraglutide as an active comparator [28]; and STEP 10 studied participants with obesity and prediabetes [29].

Human trials — liver, heart failure and other endpoints

Newsome and colleagues reported a placebo-controlled phase 2 trial in non-alcoholic steatohepatitis [30]. The phase 3 ESSENCE trial randomised 1,197 participants with metabolic dysfunction-associated steatohepatitis; at a planned interim analysis at week 72 of a 240-week trial, Sanyal and colleagues reported resolution of steatohepatitis without worsening of fibrosis in 62.9 per cent of 534 participants in the semaglutide group and 34.3 per cent of 266 in the placebo group [31].

STEP-HFpEF randomised 529 participants with heart failure with preserved ejection fraction and obesity over 52 weeks, reporting change in the Kansas City Cardiomyopathy Questionnaire clinical summary score and change in body weight as dual primary endpoints [32]; a pooled analysis with the companion diabetes trial followed [33]. STRIDE randomised 792 participants with symptomatic peripheral artery disease and type 2 diabetes, reporting the ratio to baseline of maximum treadmill walking distance at week 52 [34].

Hendershot and colleagues reported a randomised clinical trial in 48 adults with alcohol use disorder over nine weeks, using laboratory alcohol self-administration as the primary outcome [35]. This is a small early-phase trial and is reported here as such.

Observational safety literature

Hathaway and colleagues reported a retrospective matched cohort analysis raising a possible association with non-arteritic anterior ischaemic optic neuropathy [36]. Cai and colleagues subsequently examined the same question in a larger multi-institutional dataset [37]. These are observational analyses and neither establishes causation.

Evidence gaps and limitations

The size of the trial base does not close the gaps that matter to a laboratory receiving this material, and several of those gaps are total.

Nothing in this literature was conducted with research-supplied material. Every trial cited above used manufactured product of authorised specification, with a known impurity profile, a controlled counter-ion, a validated fill and a characterised excipient system. No published study establishes that research-grade or compounded semaglutide is chemically or pharmacologically equivalent to the material studied. The FDA has stated it does not have information on whether the salt forms in circulation share the properties of the approved active ingredient. Applying trial findings to a differently sourced solid is an unsupported inference, not a small one.

No published peer-reviewed stability data exists for reconstituted research-grade material. Storage guidance in circulation for such material is extrapolated from general peptide chemistry and from the authorised formulations, which contain buffers and stabilisers that a plain lyophilised powder does not.

Duration is bounded. The longest follow-up in the cardiovascular literature is a mean of 47.5 months in SOUL [22] and 39.8 months in SELECT [17]. The MASH result is a planned interim analysis at week 72 of a trial designed to run to 240 weeks [31]; the clinical outcome data from that trial are not yet complete.

Several endpoints rest on a single study. The alcohol use disorder trial enrolled 48 participants over nine weeks [35]. STRIDE [34] and STEP-HFpEF [32] are each individual trials in their respective populations. A finding from one trial is a finding from one trial.

The optic neuropathy question is unresolved. Two observational analyses [36, 37] disagree in emphasis, and observational designs of this kind cannot separate the compound from the conditions it is prescribed for.

Discontinuation. STEP 4 used a randomised withdrawal design specifically to examine the divergence between continued and discontinued groups [26], which is the reason that trial exists and a reason the single-arm trial results should not be read as describing a permanent state.

Regulatory and standards position

United Kingdom. Semaglutide is the active ingredient of medicines authorised by the Medicines and Healthcare products Regulatory Agency. Ozempic (subcutaneous) and Rybelsus (oral tablets) hold authorisations for type 2 diabetes, and Wegovy holds an authorisation for weight management. All are prescription-only medicines. Under the Human Medicines Regulations 2012 it is an offence to sell or supply a prescription-only medicine other than in accordance with a prescription, and to place an unauthorised medicinal product on the market. Medicinal products authorised centrally by the European Medicines Agency apply in Northern Ireland under the Windsor Framework.

Advertising. Advertising a prescription-only medicine to the general public is prohibited in the United Kingdom. The Committee of Advertising Practice issued an Enforcement Notice jointly with the MHRA in January 2021 naming semaglutide and liraglutide, stating that advertisers must not directly or indirectly promote prescription-only medicines to the public, including online, on social media and through influencers.

Controlled-drug status. Semaglutide is not a controlled drug. It is not scheduled under the Misuse of Drugs Act 1971 or the Misuse of Drugs Regulations 2001. Its restriction in the United Kingdom is entirely a medicines-law restriction, not a drugs-law one.

European Union. Ozempic, Rybelsus and Wegovy hold centralised marketing authorisations granted by the European Commission on the recommendation of the European Medicines Agency.

United States. The Food and Drug Administration approved Ozempic in December 2017, Rybelsus in September 2019 and Wegovy in June 2021. All are prescription products.

World Anti-Doping Agency. Semaglutide is not on the WADA Prohibited List. It is not prohibited in competition or out of competition, and no therapeutic use exemption is required for it on prohibited-list grounds. It is, however, on the WADA Monitoring Program: semaglutide was added to the Monitoring Program in 2024, and from 1 January 2026 markers of semaglutide and of tirzepatide are monitored both in competition and out of competition, to observe possible patterns of misuse. Monitoring is not prohibition, but it does mean the substance is being watched and its status can change at a future list revision. Anyone competing under an anti-doping code should verify the current list directly rather than relying on any secondary source, including this one.

Enforcement history. This compound has a documented enforcement record on both sides of the Atlantic. The FDA has issued warning letters to sellers of unapproved semaglutide products, including products labelled “for research purposes” or “not for human consumption”, where the agency took the position that the products were nonetheless sold directly to consumers for human use with accompanying dosing information. The agency’s stated position is that such labelling does not determine intended use, and that the products are unapproved new drugs and misbranded under the Federal Food, Drug, and Cosmetic Act. The FDA has separately warned about compounded products prepared from semaglutide sodium and semaglutide acetate salts. In the United Kingdom, the MHRA has reported seizing hundreds of potentially falsified semaglutide pens since January 2023, following reports of hospitalisation associated with counterfeit pens, and UK arrests have been made for suspected supply of unlicensed medicines containing semaglutide.

Laboratory handling and safety

Semaglutide should be handled as a potent pharmacologically active substance. No compound-specific workplace exposure limit is available for it, so containment practice is determined by the class of material rather than by a published threshold.

• Dust control. The lyophilised solid is fine and static-prone. Weighing and transfer of the dry powder should take place in a balance enclosure or comparable local exhaust, not on an open bench.
• Personal protective equipment. Nitrile gloves, a fastened laboratory coat and eye protection are the minimum. Gloves should be changed rather than washed after contact with the solid.
• Route of concern. The pharmacology is systemic and the material is intended for parenteral formulation in the studies that used it, so needlestick and other parenteral exposure is the material occupational risk, ahead of dermal contact. Where needles are used for reconstitution or transfer, standard sharps handling and a sharps container apply.
• Spills. Dry spills should be dampened before collection rather than swept, to avoid raising an aerosol. Solutions should be absorbed and the surface cleaned with a detergent solution.
• Waste. Residual solid, solutions, contaminated consumables and empty vials should be disposed of as pharmaceutically active laboratory waste through the institution’s route, not to drain or general waste.
• Documentation. Where a supplier certificate of analysis exists it should be retained with the material, since the counter-ion, peptide content and impurity profile all bear on any calculation made from the label mass.

Nothing in this section should be read as a safety assessment of human exposure. It is guidance for keeping a laboratory chemical contained.

References

1. Lau J, Bloch P, Schäffer L, et al. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015;58(18):7370–7380. In vitro and preclinical characterisation. PMID 26308095
2. Hinds CE, Owen BM, Hope DCD, et al. Abolishing β-arrestin recruitment is necessary for the full metabolic benefits of G protein-biased glucagon-like peptide-1 receptor agonists. Diabetes Obes Metab. 2024;26(1):65–77. In vitro receptor pharmacology with rodent work. PMID 37795639
3. Jones B, Manchanda Y, Bitsi S, et al. In vivo and in vitro characterization of GL0034, a novel long-acting glucagon-like peptide-1 receptor agonist. Diabetes Obes Metab. 2022;24(11):2090–2101. In vitro and rodent, semaglutide as comparator. PMID 35676825
4. Gabery S, Salinas CG, Paulsen SJ, et al. Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight. 2020;5(6). Rodent. PMID 32213703
5. Brierley DI, Holt MK, Singh A, et al. Central and peripheral GLP-1 systems independently suppress eating. Nat Metab. 2021;3(2):258–273. Rodent. PMID 33589843
6. Møllerhøj MB, Veidal SS, Thrane KT, et al. Hepatoprotective effects of semaglutide, lanifibranor and dietary intervention in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH. Clin Transl Sci. 2022;15(5):1167–1186. Rodent. PMID 35143711
7. Niu S, Chen S, Chen X, et al. Semaglutide ameliorates metabolism and hepatic outcomes in an NAFLD mouse model. Front Endocrinol (Lausanne). 2022;13:1046130. Rodent. PMID 36568109
8. Chuong V, Farokhnia M, Khom S, et al. The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. JCI Insight. 2023;8(12). Rodent. PMID 37192005
9. Li X, Luo H, Zhang Y, et al. Semaglutide attenuates doxorubicin-induced cardiotoxicity by ameliorating BNIP3-Mediated mitochondrial dysfunction. Redox Biol. 2024;72:103129. Rodent. PMID 38574433
10. Marbury TC, Flint A, Jacobsen JB, Derving Karsbøl J, Lasseter K. Pharmacokinetics and Tolerability of a Single Dose of Semaglutide, a Human Glucagon-Like Peptide-1 Analog, in Subjects With and Without Renal Impairment. Clin Pharmacokinet. 2017;56(11):1381–1390. Human pharmacokinetic trial. PMID 28349386
11. Hall S, Isaacs D, Clements JN. Pharmacokinetics and Clinical Implications of Semaglutide: A New Glucagon-Like Peptide (GLP)-1 Receptor Agonist. Clin Pharmacokinet. 2018;57(12):1529–1538. Review. PMID 29915923
12. Overgaard RV, Navarria A, Ingwersen SH, Bækdal TA, Kildemoes RJ. Clinical Pharmacokinetics of Oral Semaglutide: Analyses of Data from Clinical Pharmacology Trials. Clin Pharmacokinet. 2021;60(10):1335–1348. Pooled clinical pharmacology analysis. PMID 33969456
13. Yang XD, Yang YY. Clinical Pharmacokinetics of Semaglutide: A Systematic Review. Drug Des Devel Ther. 2024;18:2555–2570. Systematic review. PMID 38952487
14. Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016;375(19):1834–1844. Randomised human trial (SUSTAIN-6), n=3,297. PMID 27633186
15. Pratley RE, Aroda VR, Lingvay I, et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018;6(4):275–286. Randomised human trial. PMID 29397376
16. Husain M, Birkenfeld AL, Donsmark M, et al. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2019;381(9):841–851. Randomised human trial (PIONEER 6). PMID 31185157
17. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221–2232. Randomised human trial (SELECT), n=17,604. PMID 37952131
18. Ryan DH, Lingvay I, Deanfield J, et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med. 2024;30(7):2049–2057. Analysis of a randomised human trial. PMID 38740993
19. Colhoun HM, Lingvay I, Brown PM, et al. Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial. Nat Med. 2024;30(7):2058–2066. Analysis of a randomised human trial. PMID 38796653
20. Deanfield J, Verma S, Scirica BM, et al. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial. Lancet. 2024;404(10454):773–786. Prespecified analysis of a randomised human trial. PMID 39181597
21. Perkovic V, Tuttle KR, Rossing P, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024;391(2):109–121. Randomised human trial (FLOW), n=3,533. PMID 38785209
22. McGuire DK, Marx N, Mulvagh SL, et al. Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes. N Engl J Med. 2025;392(20):2001–2012. Randomised human trial (SOUL), n=9,650. PMID 40162642
23. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989–1002. Randomised human trial (STEP 1), n=1,961. PMID 33567185
24. Davies M, Færch L, Jeppesen OK, et al. 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. Lancet. 2021;397(10278):971–984. Randomised human trial. PMID 33667417
25. Wadden TA, Bailey TS, Billings LK, et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021;325(14):1403–1413. Randomised human trial. PMID 33625476
26. Rubino D, Abrahamsson N, Davies M, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021;325(14):1414–1425. Randomised withdrawal human trial. PMID 33755728
27. Garvey WT, Batterham RL, Bhatta M, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022;28(10):2083–2091. Randomised human trial. PMID 36216945
28. Rubino DM, Greenway FL, Khalid U, et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022;327(2):138–150. Randomised active-comparator human trial. PMID 35015037
29. McGowan BM, Bruun JM, Capehorn M, et al. Efficacy and safety of once-weekly semaglutide 2·4 mg versus placebo in people with obesity and prediabetes (STEP 10): a randomised, double-blind, placebo-controlled, multicentre phase 3 trial. Lancet Diabetes Endocrinol. 2024;12(9):631–642. Randomised human trial. PMID 39089293
30. Newsome PN, Buchholtz K, Cusi K, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med. 2021;384(12):1113–1124. Randomised human trial (phase 2). PMID 33185364
31. Sanyal AJ, Newsome PN, Kliers I, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025;392(21):2089–2099. Randomised human trial (ESSENCE), n=1,197. PMID 40305708
32. Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2023;389(12):1069–1084. Randomised human trial (STEP-HFpEF), n=529. PMID 37622681
33. Butler J, Shah SJ, Petrie MC, et al. Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials. Lancet. 2024;403(10437):1635–1648. Pooled analysis of randomised human trials. PMID 38599221
34. Bonaca MP, Catarig AM, Houlind K, et al. Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial. Lancet. 2025;405(10489):1580–1593. Randomised human trial, n=792. PMID 40169145
35. Hendershot CS, Bremmer MP, Paladino MB, et al. Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025;82(4):395–405. Randomised human trial, n=48. PMID 39937469
36. Hathaway JT, Shah MP, Hathaway DB, et al. Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmol. 2024;142(8):732–739. Retrospective matched cohort study in humans. PMID 38958939
37. Cai CX, Hribar M, Baxter S, et al. Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy. JAMA Ophthalmol. 2025;143(4):304–314. Observational cohort study in humans. PMID 39976940
38. Kristensen SL, Rørth R, Jhund PS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019;7(10):776–785. Systematic review and meta-analysis. PMID 31422062
39. Lee MMY, Sattar N, Pop-Busui R, et al. Cardiovascular and Kidney Outcomes and Mortality With Long-Acting Injectable and Oral Glucagon-Like Peptide 1 Receptor Agonists in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Trials. Diabetes Care. 2025;48(5):846–859. Systematic review and meta-analysis. PMID 40156846

Research use only

This entry is a technical reference about a laboratory chemical and a summary of published literature. It is not a recommendation, a protocol or a statement that this compound does anything.

Semaglutide supplied as a research chemical is intended for laboratory research use only. It is not a medicinal product, it is not authorised for human or veterinary use, and it is not for use in food. It must not be administered to humans or to animals other than under an appropriate regulatory and ethical authorisation. Nothing in this entry describes an amount to use, a route, a schedule or a population, and no statement here should be read as indicating that this compound treats, prevents or improves any condition.

Semaglutide is the active ingredient of medicines authorised in the United Kingdom and elsewhere. Those authorised products are prescription-only medicines, and the trials summarised above were conducted with pharmaceutical-grade material under regulatory supervision. Material supplied for research use is a different thing, and the literature above does not describe it.