The most cited peptide studies include papers that discovered peptide hormones, invented ways to make peptides, and proved peptide drugs work. Among the landmark papers we checked in Crossref in October 2026, the 1988 discovery of endothelin led with 8,569 citations. Next came Merrifield’s 1963 solid-phase peptide synthesis paper (7,002), the LEADER liraglutide trial (6,867) and the 1999 discovery of ghrelin (6,778).[18]
There is no official top-10 list of peptide papers, and counts differ between databases. So this guide reports only counts we could verify, gives the source and date, and explains why each paper matters. New to peptides? Start at the peptide basics hub.
Landmark papers and their citation counts
Counts are from the Crossref API, retrieved October 18, 2026.[18] Crossref counts only citations from works registered with it, so the numbers run lower than Google Scholar, especially for older papers.
| Year | Paper | Why it matters | Crossref citations |
|---|---|---|---|
| 1988 | Endothelin discovered[9] | A 21-amino-acid peptide that strongly constricts blood vessels | 8,569 |
| 1963 | Solid-phase peptide synthesis[1] | Made lab peptide synthesis fast and practical | 7,002 |
| 2016 | LEADER trial[14] | First big GLP-1 heart-protection result | 6,867 |
| 1999 | Ghrelin discovered[13] | The stomach’s hunger and growth hormone-releasing peptide | 6,778 |
| 2021 | STEP 1 trial[15] | Semaglutide 2.4 mg for obesity | 5,065 |
| 1998 | Orexins discovered[12] | Brain peptides first tied to feeding behavior | 4,708 |
| 2022 | SURMOUNT-1 trial[16] | Tirzepatide for obesity | 3,758 |
| 2023 | SELECT trial[17] | Semaglutide lowered heart events without diabetes | 3,223 |
| 1973 | Somatostatin discovered[4] | Hypothalamic peptide that blocks growth hormone release | 2,799 |
| 1988 | HIV Tat protein uptake[10] | Founded the field of cell-penetrating peptides | 2,407 |
| 1981 | Atrial natriuretic factor[5] | Showed the heart makes a hormone | 2,406 |
| 1987 | Magainins discovered[8] | Frog-skin antimicrobial peptides | 1,949 |
| 1971 | GnRH sequence[3] | Structure of the hormone controlling reproduction | 1,061 |
| 1992 | Exendin-4 isolated[11] | Gila monster peptide that became exenatide | 849 |
| 1987 | GLP-1 (7-37) insulin effect[6] | Identified active GLP-1 | 741 |
| 1987 | Truncated GLP-1 from the gut[7] | Independent GLP-1 discovery | 532 |
| 1953 | Oxytocin synthesis[2] | First synthesis of a peptide hormone | 516 |
For scale, the 2021 AlphaFold protein-structure paper had 46,507 Crossref citations. It is about proteins generally rather than peptides.[21] See AlphaFold and peptide structure.
The discovery papers
Making peptides (1953 and 1963). Vincent du Vigneaud’s team synthesized oxytocin, the first peptide hormone made in a lab.[2] Bruce Merrifield then anchored the growing chain to a solid resin so reagents could be washed away between steps.[1] That method still underpins how research and drug peptides are made. Merrifield won the 1984 Nobel Prize in Chemistry.[19] See our oxytocin profile and natural vs synthetic peptides.
Brain hormones (1971 and 1973). Andrew Schally’s group sequenced the hormone now called GnRH,[3] and Roger Guillemin’s group found somatostatin.[4] The two shared the 1977 Nobel Prize in Physiology or Medicine with Rosalyn Yalow.[20] GnRH led to drugs like leuprolide and gonadorelin. Somatostatin led to octreotide.
The heart as a gland (1981). Atrial extract injected into rats caused a rapid, strong increase in sodium excretion. This was the first evidence of what became atrial natriuretic peptide.[5] Its relatives are now routine blood tests; see natriuretic peptides.
GLP-1 and exendin-4 (1987 and 1992). Two groups independently showed that a shortened form of glucagon-like peptide 1 strongly stimulates insulin release.[6][7] In 1992, exendin-4 was isolated from Gila monster venom.[11] A synthetic version became exenatide, the first GLP-1 drug, leading to liraglutide, semaglutide and tirzepatide.
Hunger and wakefulness (1998 and 1999). Orexins were reported as feeding regulators,[12] and ghrelin as a stomach peptide that releases growth hormone.[13] Ghrelin’s receptor is the target of growth hormone secretagogues such as ipamorelin and MK-677.
Antimicrobial and cell-penetrating peptides (1987 and 1988). Magainins from frog skin showed that animals make their own peptide antibiotics.[8] See our LL-37 profile. Separately, the HIV Tat protein was shown to enter cells from outside,[10] founding the field of cell-penetrating peptides.
The trials
Four randomized trials turned GLP-1-based peptides into mainstream medicines, and each is already among the most cited papers in its field.
- LEADER (2016). In 9,340 people with type 2 diabetes, liraglutide lowered major cardiovascular events to 13.0% from 14.9% on placebo.[14]
- STEP 1 (2021). Semaglutide 2.4 mg produced 14.9% average weight loss at 68 weeks, versus 2.4% on placebo.[15]
- SURMOUNT-1 (2022). Tirzepatide 15 mg produced 20.9% average weight loss at 72 weeks, versus 3.1% on placebo.[16]
- SELECT (2023). In 17,604 people with heart disease and overweight but no diabetes, semaglutide cut major heart events by 20% (6.5% vs 8.0%).[17]
These trials are cited so often partly because they are recent and large, and partly because each changed prescribing guidelines. Our GLP-1 heart outcomes guide covers the cardiovascular trials in depth.
How we chose these papers
We started from discoveries and trials that led directly to peptide medicines or whole research fields, then looked up each paper’s citation count by its DOI in Crossref on the same day.[18] We report only counts we retrieved ourselves. We did not rank papers we could not look up, and we left out large proteins such as leptin and antibodies, which are not usually called peptides. A different starting list, or a different database, would produce a different order.
Limitations of citation counts
- Database differences. Crossref undercounts older literature, which is why the 1953 oxytocin paper shows only 516.[2]
- Age bias. Older papers have had longer to collect citations, while recent trials collect them faster.
- Attention isn’t accuracy. Citations can come from critics. For how to judge a study itself, see how to read peptide research.
- What’s missing. Insulin’s discovery in the 1920s predates modern DOI-based counting, so we did not include a count for it.
What’s next
Recent highly cited work is shifting toward AI design, oral delivery and new combination hormones. The 2023 SELECT trial has already passed 3,200 Crossref citations, more than the 1973 somatostatin paper has collected in over 50 years. See peptide research highlights 2026. Why many early lab findings never reach patients is covered in animal vs human peptide studies.
Questions to discuss with a clinician
- Is the study behind a treatment I’m considering a lab discovery or a human trial?
- Has the finding been confirmed by newer, larger studies?
- How does a famous trial’s population compare with me?
