origins of type 2 diabetes medications
Open accessAbstract
The origins of diabetes medications provide an intriguing catalogue of clinical serendipity and scientific design. Use of insulin (beyond 1922) gave recognition to insulin resistance and the categorisation of type 2 diabetes (T2DM). The first sulphonylurea (carbutamide, 1956) emerged from its use as an antibacterial sulphonamide prone to cause hypoglycaemia, and biguanides were first used to treat diabetes in 1957 despite their glucose-lowering properties having been known since the 1920s. Alpha-glucosidase inhibitors arose from a screening programme for amylase inhibitors by Bayer in the 1970s and acarbose was introduced in 1990. The first thiazolidinedione (ciglitazone; not developed) was identified in a screening programme for triglyceride-lowering compounds by Takeda in the late 1970s and gave rise to pioglitazone (approved 1999), although first to market was troglitazone (from Warner Lambert 1997, withdrawn 2000). Exendin, an analogue of the incretin hormone glucagon-like peptide-1 (GLP-1), was identified in 1992 in the saliva of a lizard (Heloderma suspectum), and took until 2005 to be marketed as exenatide. To promote the efficacy of endogenous GLP-1, its rapid inactivation by the enzyme dipeptidylpeptidase-4 (DPP4) was blocked by clever molecular design of the first DPP4 inhibitors (vildagliptin and sitagliptin, approved in 2006). SGLT2 inhibitors are based on phlorizin, identified in apple tree bark (1835) and modified (2000) to avoid intestinal degradation: further modifications to increase selectivity against SGLT2 gave dapagliflozin and canagliflozin - approved 2012 and 2013, respectively, in Europe.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Injected GLP-1 receptor agonists have been used to treat type 2 diabetes since 2005, and the most recent addition to the class, semaglutide, has shown particularly strong glucose-lowering efficacy, with availability as a once daily oral formulation as well as a once weekly subcutaneous injection increasing usage options.
“Although injected GLP-1RAs have been used to treat T2DM since 2005, the most recent addition to the class, semaglutide, has shown particularly strong glucose-lowering efficacy, and its availability as a once daily oral formulation as well as a once weekly subcutaneous injection has increased usage options [11, 49].”
From Recent advances in peptide-based therapies for obesity and type 2 diabetes (2024) · cites this paper as [49]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Drucker, D. J., & Nauck, M. A. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69705-5 · Cited by 3,896 · see citing works
Bailey, C. J., & Turner, R. C. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602293340906 · Cited by 1,726 · see citing works
Self-citationGLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art
Nauck, M. A., Quast, D. R., Wefers, J., & Meier, J. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101102 · Cited by 1,647 · see citing works
Metformin: historical overview
Bailey, C. J. (2017) · Diabetologia · doi:10.1007/s00125-017-4318-z · Cited by 1,079 · see citing works
Self-citationDavies, M. J., Aroda, V. R., Collins, B. S., Gabbay, R. A., Green, J., Maruthur, N. M., Rosas, S. E., Del Prato, S., Mathieu, C., Mingrone, G., et al. (2022) · Diabetologia · doi:10.1007/s00125-022-05787-2 · Cited by 1,048 · see citing works
Eng, J., Kleinman, W. A., Singh, L., Singh, G., & Raufman, J. P. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42531-8 · Cited by 1,000 · see citing works
Deacon, C. F., Nauck, M. A., Toft-Nielsen, M.-B., Pridal, L., Willms, B., & Holst, J. J. (1995) · Diabetes · doi:10.2337/diabetes.44.9.1126 · Cited by 878 · see citing works
Rossetti, L., Smith, D. J., Shulman, G. I., Papachristou, D. N., & DeFronzo, R. A. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112981 · Cited by 808 · see citing works
The internal secretion of the pancreas
Banting, F., & BEST, C. H. (1922) · Journal of Laboratory and Clinical Medicine · doi:10.5555/uri:pii:s0022214322903841 · Cited by 785 · see citing works
Intestinal Absorption of Sugars
Crane, R. K. (1960) · Physiological Reviews · doi:10.1152/physrev.1960.40.4.789 · Cited by 668 · see citing works
Meng, W., Ellsworth, B. A., Nirschl, A. A., McCann, P. J., Patel, M., Girotra, R. N., Wu, G., Sher, P. M., Morrison, E. P., Biller, S. A., et al. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm701272q · Cited by 634 · see citing works
Oates, J. A., Wood, A. J. J., & Gerich, J. E. (1989) · New England Journal of Medicine · doi:10.1056/nejm198911023211805 · Cited by 476 · see citing works
Metformin: its botanical background
Bailey, C. J., & Day, C. (2004) · Practical Diabetes · doi:10.1002/pdi.606 · Cited by 353 · see citing works
Self-citationSGLT inhibitors in management of diabetes
Tahrani, A. A., Barnett, A. H., & Bailey, C. J. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70050-0 · Cited by 333 · see citing works
Self-citationSulfonylurea Receptors, Ion Channels, and Fruit Flies
Boyd, A. E. (1988) · Diabetes · doi:10.2337/diab.37.7.847 · Cited by 281 · see citing works
Insulinotropic meglitinide analogues
Dornhorst, A. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06715-0 · Cited by 229 · see citing works
Thornberry, N. A., & Weber, A. E. (2007) · Current Topics in Medicinal Chemistry · doi:10.2174/156802607780091028 · Cited by 202 · see citing works
Sohda, T., MIZUNO, K., Imamiya, E., Sugiyama, Y., Fujita, T., & KAWAMATSU, Y. (1982) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.30.3580 · Cited by 171 · see citing works
THE ACTION OF PHLORIZIN ON THE EXCRETION OF GLUCOSE, XYLOSE, SUCROSE, CREATININE AND UREA BY MAN
Chasis, H., Jolliffe, N., & Smith, H. W. (1933) · Journal of Clinical Investigation · doi:10.1172/jci100559 · Cited by 152 · see citing works
Werner, E. A., & Bell, J. (1922) · Journal of the Chemical Society Transactions · doi:10.1039/ct9222101790 · Cited by 149 · see citing works
From the Incretin Concept and the Discovery of GLP-1 to Today's Diabetes Therapy
Holst, J. J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00260 · Cited by 148 · see citing works
Diabetes Mellitus: Its differentiation into insulin-sensitive and insulin-insensitive types
Himsworth, H. P. (2013) · International Journal of Epidemiology · doi:10.1093/ije/dyt203 · Cited by 112 · see citing works
The Current Drug Treatment Landscape for Diabetes and Perspectives for the Future
Bailey, C. J. (2015) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.144 · Cited by 101 · see citing works
Self-citationUeber Versuche einer specifischen Fermenttherapie des Diabetes
Zuelzer, G. (1908) · Zeitschrift für Experimentelle Pathologie und Therapie · doi:10.1007/bf02661302 · Cited by 69 · see citing works
Lebovitz, H. E. (1992) · Drugs · doi:10.2165/00003495-199200443-00004 · Cited by 66 · see citing works
Die Wirkung des Biguanids und seiner Derivate auf den Zuckerstoffwechsel
Hesse, E., & Taubmann, G. (1929) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf02000097 · Cited by 56 · see citing works
Garrino, M. G., Schmeer, W., Nenquin, M., Meissner, H. P., & Henquin, J. (1985) · Diabetologia · doi:10.1007/bf00291979 · Cited by 54 · see citing works
The Pioglitazone Trek via Human PPAR Gamma: From Discovery to a Medicine at the FDA and Beyond
Devchand, P. R., Liu, T., Altman, R. B., FitzGerald, G. A., & Schadt, E. E. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01093 · Cited by 54 · see citing works
Flumamine, a new synthetic analgesic and anti-flu drug.
GARCIA, E. Y. (1950) · PubMed · Cited by 51 · see citing works
Treatment of type 2 diabetes: future approaches
Bailey, C. J., & Day, C. (2018) · British Medical Bulletin · doi:10.1093/brimed/ldy013 · Cited by 48 · see citing works
Self-citationLoubatières, A. (1957) · Diabetes · doi:10.2337/diab.6.5.408 · Cited by 44 · see citing works
Hadden, D. R. (2005) · PubMed · Cited by 38 · see citing works
Safety of antidiabetes medications: An update
Bailey, C. J. (2015) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.125 · Cited by 33 · see citing works
Self-citationInhibition of sucrase by tris in rat and man, demonstrated by oral loading tests with sucrose
Puls, W., & Keup, U. (1975) · Metabolism · doi:10.1016/0026-0495(75)90010-4 · Cited by 29 · see citing works
Jörgens, V. (2018) · Acta Diabetologica · doi:10.1007/s00592-018-1206-z · Cited by 21 · see citing works
Sulfonylureas: Basic Aspects and Clinical Uses
Lebovitz, H. E., & Melander, A. (2004) · Wiley eBooks · doi:10.1002/0470862092.d0608 · Cited by 20 · see citing works
Diem, P., Ducluzeau, P., & Scheen, A. J. (2021) · Diabetes Epidemiology and Management · doi:10.1016/j.deman.2021.100049 · Cited by 14 · see citing works
Foley, J. E., & Åhrén, B. (2017) · touchREVIEWS in Endocrinology · doi:10.17925/ee.2017.13.02.56 · Cited by 13 · see citing works
The hypocaloric diet in type 2 diabetes - déjà vu
Day, C., & Bailey, C. J. (2012) · The British Journal of Diabetes · doi:10.1177/1474651412437503 · Cited by 9 · see citing works
Self-citation[From the discovery of phlorizin (a Belgian story) to SGLT2 inhibitors].
Valdés-Socin, H., Scheen, A. J., Jouret, F., Grosch, S., & Delanaye, P. (2022) · PubMed · Cited by 4 · see citing works
Alberti, K. G. M. M., & Bailey, C. J. (2022) · British Journal of Diabetes · doi:10.15277/bjd.2022.352 · Cited by 1 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 12
- Tattersall R. Pancreatic organotherapy for diabetes, 1889-1921. Med Hist 1995;39:288-316. https://doi.org/10.1017/s002572730060087 · DOI
- Paulescu NC. Recherches sur le rôle du pancréas dans l'assimilation nutritive. Arch Int Physiol 1921;17:85-109.
- Lister J, Nash J, Ledingham U. Constitution and insulin sensitivity in dia- betes mellitus. Br Med J 1951;1[4703]:376-9. https://doi.org/10.1136/ bmj.l.4703.376 · DOI
- Sterne J. Du nouveau dans les antidiabétiques. La NN dimethylamine guanyl guanidine (N.N.D.G.) Maroc Med 1957; 36: 1295-1296 [article in French]
- Janbon M, Chaptal J, Vedel A, Schaap J. Accidents hypoglycémiques graves par un sulfamidothiodiazol (le VK 57 ou 2254 RP). Montpellier Med 1942; 441:21-22.
- Tattersall R. Discovery of the sulphonylureas. Diabetes on the Net 2008;7: 74. https://diabetesonthenet.com/diabetes-digest/discovery-of-the-sulpho- nylureas/ Accessed 21 October 2022.
- Kleinsorge H. Carbutamide -the first oral antidiabetic. A retrospect. Exp Clin Endocrinol Diabetes 1998;106:149-51. https://doi.org/10.1055/s-0029- 12119687 · DOI
- Geisen K, Hübner M, Hitzel V, et al. Acylaminoalkyl substituted benzoic and phenylalkane acids with hypoglycaemic properties. Arzneimittelforschung 1978;28:1081-3.PMID:582693
- Kaul S, Bolger AF, Herrington D, Giugliano RP, Eckel RH. Thiazolidinedione drugs and cardiovascular risks: A Science Advisory from the American Heart Association and American College of Cardiology Foundation. J Am Coll Car- diol 2010;55:1885-94. https://doi.org/10.1016/j/jacc.2020.02.014 · DOI
- De Block C, Bailey C, Wysham C, Hemmingway A, Allen SE, Peleshok J. Tirzepatide for the treatment of adults with type 2 diabetes: An endocrine perspective. Diabetes Obes Metab 2022; https://doi.org/10.1111/ dom.14831. Online ahead of print. · DOI
- Villhauer EB, Brinkman JA, Naderi GB, et al. 1-[[(3-hydroxy-1- adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem 2003;46:2774-89. https://doi.org/10.1021/ jm0300911 · DOI
- McGuire DK, Shih WJ, Cosentino F, et al. Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta- analysis. JAMA Cardiol 2021;6:148-58. https://doi.org/10.1001/ jamacar- dio.2020.4511 · DOI
Cited by
Sorted by citations
Metformin: Therapeutic profile in the treatment of type 2 diabetes
Bailey, C. J. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15663 · Cited by 131 · see citing works
Self-citationRecent advances in peptide-based therapies for obesity and type 2 diabetes
Bailey, C. J., Flatt, P. R., & Conlon, J. M. (2024) · Peptides · doi:10.1016/j.peptides.2024.171149 · Cited by 25 · see citing works
Self-citationRehman, A., Satyam, S. M., El‐Tanani, M., Prabhakar, S., KUMARI, R. R., Shetty, P., Mohammed, S. S. N., Nafees, Z., & Alomar, B. (2025) · Cancers · doi:10.3390/cancers17152466 · Cited by 17 · see citing works
Pharmacological therapies for type 2 diabetes: future approaches
Bailey, C. J. (2025) · Diabetologia · doi:10.1007/s00125-025-06581-6 · Cited by 19 · see citing works
Self-citationGuraka, A., Sreedharan, S., Arasaradnam, R. P., Tripathi, G., & Kermanizadeh, A. (2024) · Nutrition Reviews · doi:10.1093/nutrit/nuae172 · Cited by 5 · see citing works
Subramani, R. M., Jayaseelan, S. P., Shamprasad, B. R., Arumugam, R., Saravanan, A. A., Prashanth, M. S., Munuswamy‐Ramanujam, G., & Sivasubramanian, A. (2025) · ChemistrySelect · doi:10.1002/slct.202500486 · Cited by 4 · see citing works
Ramadori, G. P. (2025) · Livers · doi:10.3390/livers5030035 · Cited by 2 · see citing works
Iacob, A. D., Cioancă, O., Aprodu, I., Tatia, R., Iacob, A.-T., Mircea, C., Tutunaru, D., Pavel, A. B., Lungu, I. I., & Dragostin, O. M. (2026) · Pharmaceuticals · doi:10.3390/ph19040538 · Cited by 1 · see citing works
Teufel, F., Theilmann, M., Marcus, M. E., Sulola, M. A., Guwatudde, D., Quintana, H. K., Banegas, J. R., Soniwala, A., Kim, S., Aryal, K., et al. (2026) · Diabetes Care · doi:10.2337/dc26-0267 · Cited by 1 · see citing works
Perspective Chapter: Metformin Origins, Clinical Trials, and Impact in Pharmacy
Tenpas, A. S., Stout, H. K., & Infante, A. F. (2025) · Pharmaceutical science. · doi:10.5772/intechopen.1012525
Ansari, B., Jan, M. S., Pirzada, A. S., Khan, A., Pervaiz, A., Alsharif, K. F., Daglia, M., Elhenawy, A. A., & Khan, H. (2026) · Scientific Reports · doi:10.1038/s41598-026-62283-y
Mechanisms of Hepatic Insulin Resistance and Its Contribution to the Pathogenesis of Type 2 Diabetes
Onyango, A. N. (2026) · Comprehensive physiology · doi:10.1002/cph4.70285
- Authors
- Bailey, C. J.
- Affiliations
- Aston University (GB)
- Corresponding author
- Bailey, Clifford J
- ORCID
- Bailey, Clifford J
- Venue
- British Journal of Diabetes
- Publisher
- ABCD Diabetes Care, Ltd.
- Published
- 2022-12-21
- Volume
- 22
- Issue
- 2
- Pages
- 112-120
- ISSN
- 2397-6233 (ISSN-L)
- 2397-6241
- OpenAlex
- W4312190013
- Cited by
- 12
- References
- 41
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 3
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- British Journal of Diabetes (publishedVersion)
- British Journal of Diabetes (publishedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Historical Medical Research and Treatments
- Keywords
- type 2 diabetes, antidiabetic drugs, history of drug discovery, insulin, insulin resistance, sulfonylureas, carbutamide, biguanides, alpha-glucosidase inhibitors, acarbose, thiazolidinediones, pioglitazone, exenatide, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors, phloridzin, drug screening
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
