Liraglutide Research History: Discovery, Key Trials and Regulatory Timeline

Liraglutide is a prescription medicine: an analogue of the human incretin hormone glucagon-like peptide-1 (GLP-1) that acts at the GLP-1 receptor. This page summarises how the molecule was designed, which published studies and reviews shaped its evidence base, and how the literature describes its regulatory position. It is a history page, not a how-to: questions about whether any medicine is appropriate for a particular person belong with a prescribing clinician. This page is for educational purposes only and is not medical advice; consult a licensed physician for any question about diagnosis, treatment or medication.

Origins: how liraglutide was designed

Native GLP-1 is cleared from the circulation within minutes, which made the unmodified hormone impractical as a medicine. The problem and the chemistry used to solve it were set out in a 2019 review in Frontiers in Endocrinology, which described the discovery and development of both liraglutide and semaglutide and explained that liraglutide was created by attaching a fatty-acid side chain to a GLP-1 backbone so that the resulting peptide binds reversibly to serum albumin and circulates far longer than the native hormone (PMID 31031702). That same 2019 review described the acylation strategy as the central design idea behind the molecule and traced how it was carried forward into later GLP-1 analogue work (PMID 31031702).

Chronologically, the question “who discovered liraglutide” is best answered as a programme rather than a person. The peptide emerged from an industrial GLP-1 analogue research programme whose chemistry and pharmacology the 2019 review documented in detail, including the rationale for albumin-mediated protraction (PMID 31031702). The verified literature cited on this page does not name individual discoverers, and no names are asserted here.

Liraglutide as a chemical template

The clearest marker of liraglutide’s place in peptide chemistry is that it became the starting point for the next generation of GLP-1 analogues. A 2015 paper in the Journal of Medicinal Chemistry on the discovery of the once-weekly GLP-1 analogue semaglutide described how structural modification of the liraglutide scaffold — including changes to the acyl chain and the peptide backbone — was used to extend the half-life further (PMID 26308095). Researchers in that 2015 report framed the work explicitly as building on the earlier once-daily analogue (PMID 26308095), and the 2019 review later presented the two molecules as a single continuous development story (PMID 31031702).

Key published studies in chronological order

2015 — first signals in case-level safety reporting

A 2015 report in Aging Clinical and Experimental Research described liraglutide-related cholelithiasis, placing gallstone disease into the published safety narrative for the medicine (PMID 25725635). The same year, the medicinal-chemistry record of the analogue class was extended by the semaglutide discovery paper described above (PMID 26308095).

2016 — placement within obesity pharmacotherapy reviews

By 2016, a review of pharmacotherapy for obesity in Endocrinology and Metabolism Clinics of North America discussed liraglutide among the pharmacological options available to clinicians treating obesity, alongside other agents in that therapeutic category (PMID 27519128). The inclusion of the medicine in a mainstream review of approved obesity pharmacotherapy by that date is itself a dated marker of its regulatory position (PMID 27519128).

2017 — renal outcomes reported from the cardiovascular outcome trial programme

One of the most frequently cited entries in the liraglutide record is the 2017 New England Journal of Medicine report on liraglutide and renal outcomes in type 2 diabetes (PMID 28854085). In that trial, researchers reported fewer events of the prespecified renal composite outcome in the liraglutide group than in the placebo group, with the difference driven mainly by lower rates of new-onset persistent macroalbuminuria (PMID 28854085). The study was a secondary analysis of a large randomised, placebo-controlled cardiovascular outcomes trial, and its authors reported the renal findings as prespecified secondary endpoints rather than as a primary demonstration of renal benefit (PMID 28854085).

2018 — preclinical mechanism work on vascular disease

A 2018 study in JACC: Basic to Translational Science reported that the GLP-1 analogues liraglutide and semaglutide reduced atherosclerosis in ApoE(−/−) and LDLr(−/−) mice, and the researchers attributed the effect to a mechanism that included inflammatory pathways (PMID 30623143). That work was conducted in genetically modified mouse models, and the authors framed it as mechanistic rather than clinical evidence (PMID 30623143).

2019 — the consolidated discovery narrative

The 2019 Frontiers in Endocrinology review brought the chemistry, pharmacology and development history of liraglutide together in one place, and remains the principal published account of how the molecule came to exist (PMID 31031702).

2024 — cardiac mechanism studies in animals

A 2024 study in Acta Pharmacologica Sinica reported that empagliflozin and liraglutide ameliorated heart failure with preserved ejection fraction (HFpEF) in mice, and the researchers identified augmentation of the Erbb4 signalling pathway as a contributing mechanism (PMID 38589689). As with the 2018 atherosclerosis work, these were animal findings reported at a mechanistic level (PMID 38589689).

2025–2026 — review-level synthesis across populations and indications

Recent reviews have examined where GLP-1 receptor agonists including liraglutide sit across different patient groups and conditions. A 2025 review in Medicina Clinica examined GLP-1 receptor agonists and GIP/GLP-1 co-agonists in the treatment of obesity in adolescents and the elderly (PMID 40716192). A 2025 critical review in Sleep Medicine Reviews assessed randomised placebo-controlled trials of pharmacotherapy for obstructive sleep apnoea, a field in which GLP-1-based agents have been studied (PMID 40974973). A 2026 FP Essentials review addressed obesity management pharmacotherapy for primary-care audiences (PMID 42101582), and a 2026 review in JBRA Assisted Reproduction summarised what is currently known about GLP-1 receptor agonists and fertility (PMID 42441883).

Publication timeline at a glance

Regulatory status as the literature describes it

Liraglutide is a prescription medicine, supplied and used under the supervision of a licensed prescriber. The published record places it inside standard therapeutic reviews rather than outside them: a 2016 review of obesity pharmacotherapy treated it as one of the available pharmacological options for weight management (PMID 27519128), and subsequent reviews have continued to discuss it alongside other GLP-1-based agents in obesity care for adolescents and older adults (PMID 40716192) and in primary-care obesity management (PMID 42101582). Its use in type 2 diabetes is reflected in the large randomised cardiovascular outcomes trial programme from which the 2017 renal analysis was drawn (PMID 28854085).

Exact marketing-authorisation dates vary by country and by indication, and the papers cited on this page do not list them. Readers who need the authoritative approval date for a particular jurisdiction or product should consult the relevant national regulator’s public records or the approved product labelling; questions about whether the medicine is suitable for an individual are for a prescribing clinician. Nothing on this page is legal or medical advice.

Adverse Events in the Liraglutide Literature: What Studies Report

Safety reporting runs alongside the efficacy literature throughout the timeline. A 2015 case report described liraglutide-related cholelithiasis, bringing gallbladder events into the published record for the medicine (PMID 25725635). A 2025 review in The Laryngoscope catalogued otolaryngologic side effects reported in association with GLP-1 receptor agonists as a class (PMID 39936458). Reviews of obesity pharmacotherapy have likewise discussed tolerability as part of agent selection (PMID 27519128, PMID 42101582). Reported adverse events in published studies describe what was observed in those study populations; they are not a prediction for any individual, and adverse-event questions should be taken to a clinician.

What the history shows — and what remains open

• A chemistry-led origin. The molecule exists because acylation extended the half-life of a rapidly degraded native hormone, as the 2019 review described (PMID 31031702).
• A template effect. Later analogue development used the same strategy, documented in the 2015 semaglutide discovery paper (PMID 26308095).
• Outcome-trial data beyond glycaemia. The 2017 renal analysis reported secondary endpoint differences in a placebo-controlled trial population (PMID 28854085).
• Mechanistic work continuing in animals. Atherosclerosis in mice in 2018 (PMID 30623143) and HFpEF in mice in 2024 (PMID 38589689).
• Open questions. Reviews published in 2025 and 2026 noted areas where evidence is still developing, including obstructive sleep apnoea pharmacotherapy (PMID 40974973) and fertility (PMID 42441883).

Related reading

For a plain-language overview of the molecule itself, see the liraglutide learn page.

References

• The Discovery and Development of Liraglutide and Semaglutide (Frontiers in Endocrinology, 2019)
• Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide (Journal of Medicinal Chemistry, 2015)
• Liraglutide-related cholelithiasis (Aging Clinical and Experimental Research, 2015)
• Pharmacotherapy for Obesity (Endocrinology and Metabolism Clinics of North America, 2016)
• Liraglutide and Renal Outcomes in Type 2 Diabetes (The New England Journal of Medicine, 2017)
• The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE(-/-) and LDLr(-/-) Mice by a Mechanism That Includes Inflammatory Pathways (JACC: Basic to Translational Science, 2018)
• Empagliflozin and liraglutide ameliorate HFpEF in mice via augmenting the Erbb4 signaling pathway (Acta Pharmacologica Sinica, 2024)
• Otolaryngologic Side Effects of GLP-1 Receptor Agonists (The Laryngoscope, 2025)
• GLP-1 receptor agonists and GIP/GLP-1 co-agonists in the treatment of obesity in adolescents and the elderly (Medicina Clinica, 2025)
• Pharmacotherapy for obstructive sleep apnea: a critical review of randomized placebo-controlled trials (Sleep Medicine Reviews, 2025)
• Obesity Management: Pharmacotherapy (FP Essentials, 2026)
• GLP-1 Receptor Agonists and Fertility: What Is Known So Far? (JBRA Assisted Reproduction, 2026)