DPP4 dipeptidyl peptidase 4
ENSG00000197635 · protein coding · Open Targets profile
Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T- cell activation (PubMed:10900005, PubMed:10951221, PubMed:11772392, PubMed:17287217). Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC (PubMed:10900005, PubMed:10951221, PubMed:11772392, PubMed:14691230). Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (PubMed:17287217). Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion (PubMed:11772392). In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM (PubMed:10593948, PubMed:16651416). May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation (PubMed:18708048). When overexpressed, enhanced cell proliferation, a process inhibited by GPC3 (PubMed:17549790). Also acts as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones such as brain natriuretic peptide 32 (PubMed:10570924, PubMed:16254193). Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline (PubMed:10593948). {ECO:0000269|PubMed:10570924, ECO:0000269|PubMed:10593948, ECO:0000269|PubMed:10900005, ECO:0000269|PubMed:10951221, ECO:0000269|PubMed:11772392, ECO:0000269|PubMed:14691230, ECO:0000269|PubMed:16254193, ECO:0000269|PubMed:16651416, ECO:0000269|PubMed:17287217, ECO:0000269|PubMed:17549790, ECO:0000269|PubMed:18708048}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- Advanced Clinical, UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.7595599889755249 (upper bound 0.9024500250816345). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 164 registry trials, updated in the last three years, of the most advanced drugs against DPP4 (trelagliptin, gemigliptin, sitagliptin, evogliptin, sitagliptin hydrochloride monohydrate, teneligliptin, saxagliptin, omarigliptin, vildagliptin, alogliptin benzoate, alogliptin, linagliptin), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Kazuoki KondoTanabe Pharma Corporation · 10 of 10 trials Phase 2+
- Takashi KadowakiTokyo University · 10 of 10 trials Phase 2+
- General ManagerTanabe Pharma Corporation · 3 of 3 trials Phase 2+
- Haidy Mahmoud SamiDelta University · 2 of 2 trials Phase 2+
- Abraham S ÁlvarezOncológico Potosino (Red OSMO) · 1 of 1 trials Phase 2+
- ahmed husseinoctober 6 university hospital · 1 of 1 trials Phase 2+
- Alexandre KLEINHospices Civils de Colmar · 1 of 1 trials Phase 2+
- Aliena BadshahKhyber Teaching Hospital · 1 of 1 trials Phase 2+
- Amber L BeitelsheesUniversity of Maryland, Baltimore · 1 of 1 trials Phase 2+
- Ana L Flores BarrancoOaxaca Site Management Organization SC. (Red OSMOS) · 1 of 1 trials Phase 2+
- Anil BhansaliPost Graduate Institute of Medical Education and Research, Chandigarh · 1 of 1 trials Phase 2+
- Antonio LlombartMedSIR · 1 of 1 trials Phase 2+
- Atef A BassyouniMedical consultant . National Institute of Diabetes and Endocrinology · 1 of 1 trials Phase 2+
- Aya Emad FoudaClinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University · 1 of 1 trials Phase 2+
- Brian RobertsMetabolex, Inc. · 1 of 1 trials Phase 2+
Registry trials of trelagliptin, gemigliptin, sitagliptin, evogliptin, sitagliptin hydrochloride monohydrate, teneligliptin, saxagliptin, omarigliptin, vildagliptin, alogliptin benzoate, alogliptin, linagliptin updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 143 of 151 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 13 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
78 trials of drugs against DPP4 were stopped early; 11 give no reason
Terminated, withdrawn and suspended interventional trials of trelagliptin, gemigliptin, sitagliptin, evogliptin, sitagliptin hydrochloride monohydrate, teneligliptin, saxagliptin, omarigliptin, vildagliptin, alogliptin benzoate, alogliptin, linagliptin, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 78.
- withdrawn · 2026-10-16 · Sun Yat-sen University · Linagliptin“The study was withdrawn because the protocol was revised and would be replaced by an updated study design, prior to participant enrollment.”
- terminated · 2026-10-07 · Institut National de la Santé Et de la Recherche Médicale, France · Sitagliptin“New treatments available, which prevents additional recruitment.”
- terminated · 2026-08-18 · REDNVIA Co., Ltd. · Evogliptin“The study is terminated due to sponsor's business decision. There were no safety issues influencing this course of action.”
- terminated · 2026-08-03 · Hoffmann-La Roche · Linagliptin“The study was closed because the sponsor decided not to continue the development of certain treatment combinations.”
- terminated · 2026-05-12 · Hoffmann-La Roche · Linagliptin“Study was closed early as the sponsor decided not to continue development of certain treatment combinations.”
- withdrawn · 2025-12-18 · Eurofarma Laboratorios S.A. · matched by the registry's drug synonyms“Strategic change in development priorities”
- terminated · 2025-08-03 · Vanderbilt University Medical Center · Sitagliptin“An alternative study was developed to replace this study.”
- withdrawn · 2025-07-14 · Sadat City University · Vildagliptin 50 MG“Institutional and funding constrains”
- withdrawn · 2025-07-14 · Sadat City University · Vildagliptin 50 MG“Institutional and funding constrains”
- withdrawn · 2024-09-19 · George Medicines PTY Limited · GMRx-4 IR polypill - sitagliptin, dapagliflozin, metformin“The sponsor has determined that this study will be postponed due to changing business priorities.”
- withdrawn · 2024-04-29 · Indiana University · Sitagliptin“PI has left IU with no plan to initiate study at IU”
- terminated · 2023-11-28 · RenJi Hospital · Linagliptin“Difficult in enrolling suitable participants”
- terminated · 2023-09-13 · University of Nebraska · Sitagliptin“lack of funding”
- terminated · 2023-06-05 · Sabyasachi Sen · Saxagliptin 5mg“Sponsor did not want to continue funding the study”
- suspended · 2023-04-07 · Oregon Health and Science University · Saxagliptin“Funding”
- terminated · 2023-02-16 · Erasme University Hospital · matched by the registry's drug synonyms“Recruitment too slow”
- withdrawn · 2022-11-15 · Icahn School of Medicine at Mount Sinai · Exendin 9-39 and SitagliptinNo reason given
- withdrawn · 2022-07-27 · EMS · matched by the registry's drug synonyms“Sponsor decision”
- terminated · 2022-05-31 · AstraZeneca · Saxagliptin 5 mg“Sponsor decided to stop commercialization of QTERNMet/Qtrilmet and to stop all related ongoing activities/studies for business reasons.”
- withdrawn · 2022-03-24 · University at Buffalo · sitagliptin“Study funding was for 1 year to a fellow who graduated in early stages of enrollment. While 6 patients were enrolled, many patients didn't finish the study and therefore little data was collected and no results will be entered.”
- withdrawn · 2021-10-11 · Rush University Medical Center · metformin and sitagliptin“No subjects enrolled.”
- withdrawn · 2021-06-10 · University of Miami · Linagliptin“Logistical challenges amid COVID-19 pandemic and lack of financial support”
- terminated · 2021-06-02 · Rabin Medical Center · Linagliptin 5 MG“End of COVID-19 outbreak in Israel”
- terminated · 2020-12-17 · Novartis · Vildagliptin“After analysis of the existing data, it was determined that additional skin biopsy samples would not be required to determine study outcome.”
- withdrawn · 2020-09-02 · Johann Wolfgang Goethe University Hospital · Vildagliptin“insufficient recruitment”
Paediatric incentives and obligations for DPP4's drugs
For trelagliptin, gemigliptin, sitagliptin, evogliptin, sitagliptin hydrochloride monohydrate, teneligliptin, saxagliptin, omarigliptin, vildagliptin, alogliptin benzoate, alogliptin, linagliptin: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · DPP4 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000230006 (empagliflozin / sitagliptin, Treatment of type 2 diabetes mellitus): W: decision granting a waiver in all age groups for all conditions or indications, 21 Mar 2025; EMEA-003572-PIP01-23 (sitagliptin;dapagliflozin, Treatment of type II diabetes mellitus): W: decision granting a waiver in all age groups for all conditions or indications, 21 Jun 2024; EMEA-003534-PIP01-23 (sitagliptin;dapagliflozin, Treatment of type II diabetes mellitus): W: decision granting a waiver in all age groups for all conditions or indications, 12 Apr 2024; EMEA-003486-PIP01-23 (sitagliptin;dapagliflozin, Treatment of type 2 diabetes mellitus): W: decision granting a waiver in all age groups for all conditions or indications, 29 Dec 2023; +15 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names trelagliptin, gemigliptin, sitagliptin, evogliptin, sitagliptin hydrochloride monohydrate, teneligliptin, saxagliptin, omarigliptin, vildagliptin, alogliptin benzoate, alogliptin, linagliptinRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Sitagliptin SUN: authorised since 9 Dec 2021; Trajenta: authorised since 23 Aug 2011; Sitagliptin / Metformin hydrochloride Mylan: authorised since 16 Feb 2022; Qtern: authorised since 15 Jul 2016; +27 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of trelagliptin, gemigliptin, sitagliptin, evogliptin, sitagliptin hydrochloride monohydrate, teneligliptin, saxagliptin, omarigliptin, vildagliptin, alogliptin benzoate, alogliptin, linagliptinRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 37 interventional studies of trelagliptin, gemigliptin, sitagliptin, evogliptin, sitagliptin hydrochloride monohydrate, teneligliptin, saxagliptin, omarigliptin, vildagliptin, alogliptin benzoate, alogliptin, linagliptin include patients under 18; 3 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 21 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.