The origins of type 2 diabetes medications
DOI:
https://doi.org/10.15277/bjd.2022.388Keywords:
type 2 diabetes, glucose-lowering agents, history, glycaemic controlAbstract
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and gave rise to pioglitazone (approved 1999), although first to market was troglitazone (from Warner Lambert 1997, withdrawn 2000).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.
References
Bailey CJ, Day C. Treatment of type 2 diabetes: future approaches. Brit Med Bull 2018;126:123-37. https://doi.org/10.1093/brimed/ldy013
Bailey CJ. The current drug treatment landscape for diabetes and perspectives for the future. Clin Pharmacol Ther 2015;98:170-84. https://doi.org/10.1002/cpt.144
Bliss Michael. The discovery of insulin. Toronto: McClelland & Stewart; 1982.
Tattersall R. Pancreatic organotherapy for diabetes, 1889-1921. Med Hist 1995;39:288–316. https://doi.org/10.1017/s002572730060087
Alberti KGMM, Bailey CJ. The discovery of insulin. Brit J Diabetes 2022; 22(Supp1):S3-S5. https://doi.org/10.15277/bjd.2022.352
Diema P, Ducluzeaub PH, Scheen A. The discovery of insulin. Diabetes Epidemiology Management 2022;5:100049. https://doi.org/10.1016/j.deman.2021.100049 Accessed 18 October 2022.
Banting FG, Best CH. The internal secretion of the pancreas. J Lab Clin Med 1922;7:251-66. PMID:17582843
Zuelzer G. Ueber Versuche einer specifischen Fermenttherapie des Diabetes. Zeitschrift für die experimentelle Pathologie und Therapie 1908;5:307–18.
Paulescu NC. Recherches sur le rôle du pancréas dans l'assimilation nutritive. Arch Int Physiol 1921;17:85–109.
Himsworth HP. Diabetes mellitus: its differentiation into insulin-sensitive and insulin-insensitive types. Lancet 1936;227:127-30. https://doi.org/10.1093/ije/dyt203
Lister J, Nash J, Ledingham U. Constitution and insulin sensitivity in diabetes mellitus. Br Med J 1951;1[4703]:376-9. https://doi.org/10.1136/bmj.l.4703.376
Hadden DR. Goat’s rue—French lilac – Italian fitch – Spanish sainfoin: gallega officinalis and metformin: the Edinburgh connection. J R Coll Physicians Edin 2005;35:258–60. PMID:16402501
Bailey CJ, Day C. Metformin: its botanical background. Pract Diabetes Int 2004;21:115–17. https://doi.org/10.1002/pdi.606
Werner EA, Bell J. The preparation of methylguanidine, and of ββ-dimethylguanidine by the interaction of dicyandiamide, and methylammonium and dimethylammonium chlorides respectively. J Chem Soc Trans 1922;121: 1790–1794. https://doi.org/10.1039/CT9222101790
Hesse G, Taubmann G. Die Wirkung des Biguanids und seiner Derivate auf den Zuckerstoffwechsel. Arch Exp Path Pharmacol 1929;142:290–308 [article in German].
Slotta KH, Tschesche R. Uber Biguanide. Die blutzuckersenkende Wirkung der Biguanides. Ber Dtsch Chem Ges 1929;62:1398–405 [article in German]. https://doi.org/10.1002/aber.10=9290620604
Garcia EY. Flumamine, a new synthetic analgesic and anti-flu drug. J Philippine Med Assoc 1950; 26:287–93. PMID: 14779282
Pasik C. Jean Sterne: a passion for research. In: Pasik C (ed) Glucophage: serving diabetology for 40 years. Lyon, Groupe Lipha, 1997; pp 29–31.
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]
Bailey CJ. Metformin: historical overview. Diabetologia 2017;60:1566-76. https://doi.org/10.1007/s00125-017-4318-z
Bailey CJ, Turner RC. Drug therapy: metformin. N Engl J Med 1996;334: 574–79. https://doi.org/10.1056/NEJM199602293340906
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.
Loubatières A. The mechanism of action of the hypoglycemic sulphonylureas: a concept based on investigations in animals and man. Diabetes 1957;6:408–17. https://doi.org/10.2337/diab.6.5.408
Tattersall R. Discovery of the sulphonylureas. Diabetes on the Net 2008;7:74. https://diabetesonthenet.com/diabetes-digest/discovery-of-the-sulphonylureas/ 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
Gerich JE. Oral hypoglycemic agents. N Engl J Med 1989;321:1231-45. https://doi.org/10.1056/NEJM198911023211805
Lebovitz HE, Melander A. Sulfonylureas: basic aspects and clinical uses. In International Textbook of Diabetes Mellitus, 3rd edition, DeFronzo RA, Ferrannini E, Keen H, Zimmet P (eds). Wiley, Cichester, 2004, 801-31. https://onlinelibrary.wiley.com/doi/abs/10.1002/0470862092.d0608
Boyd AE. Sulfonylurea receptors, ion channels, and fruit flies. Diabetes 1988;37:847-50. https://doi.org/10.2337/diab.37.7.847
Geisen K, Hübner M, Hitzel V, et al. Acylaminoalkyl substituted benzoic and phenylalkane acids with hypoglycaemic properties. Arzneimittelforschung 1978;28:1081-3.PMID:582693
Garrino G, Schmeer W, Nenquin M, Meissner HP, Henquin JC. Mechanism of the stimulation of insulin release in vitro by HB 699, a benzoic acid derivative similar to the non-sulphonylurea moiety of glibenclamide. Diabetologia 1985;28:697–703. https://doi.org/10.1007/BF00291979
Dornhorst A. Insulinotropic meglitinide analogues. Lancet 2001;358:1709-16. https://doi.org/10.1016/S0140-6736(01)06715-0
Puls W, Keup U. Inhibition of sucrase by tris in rat and man, demonstrated by oral loading tests with sucrose. Metabolism 1975;24:93-8. https://doi.org/10.1016/0026-0495(75)90010-4
Lebovitz HE. Oral antidiabetic agents. the emergence of alpha-glucosidase inhibitors. Drugs 1992;44(Suppl3):21-8. https://doi.org/10.2165/00003495-199200443-00004
Sohda T, Mizuno K, Imamiya E, et al. Studies on antidiabetic agents. II. Synthesis of 5-[4-(1-methylcyclohexylmethoxy)-benzyl]thiazolidine-2,4-dione (ADD-3878) and its derivatives. Chem Pharm Bull (Tokyo) 1982;30:3580- 600. https://doi.org/10.1248/cpb.30.3580
Devchand PR, Liu T, Altman RB, FitzGerald GA, Schadt EE. The pioglitazone trek via human PPAR gamma: from discovery to a medicine at the FDA and beyond. Front Pharmacol 2018;01093. https://doi.org/10.3389/fphar.2018.01093 Accessed 22 October 2022
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 Cardiol 2010;55:1885–94. https://doi.org/10.1016/j/jacc.2020.02.014
Bailey CJ. Safety of antidiabetes medications: an update. Clin Pharmacol Ther 2015;98:185-95. https://doi.org/10.1002/cpt.125
Holst JJ. From the incretin concept and the discovery of GLP-1 to today's diabetes therapy. Front Endocrinol 2019;00260. https://doi.org/10.3389/fendo.2019.00260 Accessed 22 October 2022
Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006;368:1696-705. https://doi.org/10.1016/S0140-6736(06)69705-5
Deacon CF, Nauck MA, Toft-Nielsen M, Pridal L, Willms B, Holst JJ. Both subcutaneously and intravenously administered glucagon-like peptide 1 are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes 1995;44:1126–31. https://doi.org/10.2337/diab.44.9.1126
Eng J, Kleinman WA, Singh L, Singh G, Raufman JP. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem 1992;267:7402-05. https://doi.org/10.1016/S0021-9258(18)42531-8
Interview with John Eng. Dr John Eng’s research found that the saliva of the Gila Monster contains a hormone that treats diabetes better than any other medicine. Diabetes in Control, 2007. https://www.diabetesincontrol.com/dr-john-engs-research-found-that-the-saliva-of-the-gila-monster-contains-a-hormone-that-treats-diabetes-better-than-any-other-medicine/ Accessed 23 October 2022
Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes – state-of-the-art. Mol Metab 2021;46: 101102. https://doi.org/10.1016/j.molmet.2020.101102
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.
Foley JE, Ahrén B. The Vildagliptin Experience — 25 years since the initiation of the Novartis glucagon-like peptide-1 based therapy programme and 10 years since the first vildagliptin registration. Eur Endocrinol 2017;13:56–61. https://doi.org/10.17925/EE.2017.13.02.56
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
Thornberry NA, Weber AE. Discovery of JANUVIA (Sitagliptin), a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Curr Top Med Chem 2007;7:557-68. https://doi.org/10.2174/156802607780091028
Jörgens V. The roots of SGLT inhibition: Laurent-Guillaume de Koninck, Jean Servais Stas and Freiherr Josef von Mering. Acta Diabetol 2019;56:29-31. https://doi.org/10.1007/s00592-018-1206-z
Valdes-Socin H, Scheen AJ, Jouret F, Grosch S, Delanaye P. From the discovery of phlorizin (a Belgian story) to SGLT2 inhibitors. Rev Med Liege 2022;77: 175-80. [article in French]. PMID:35258866
Chasis H, Jolliffe N, Smith HW. The action of phlorizin on the excretion of glucose, xylose, sucrose, creatinine and urea by man. J Clin Invest 1933;12:1083–90.
Crane RK. Intestinal absorption of sugars. Physiol Revs 1960;40:789–825. https://doi.org/10.1152/physrev.1960.40.4.789
Rossetti L, Smith D, Shulman GI, Papachristou D, DeFronzo RA. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest 1987;79:1510–15. https://doi.org/10.1172/JCI112981
Meng W, Ellsworth BA, Nirschl AA, et al. Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem 2008;51:1145–9. https://doi.org/10.1021/jm701272q
Tahrani AA, Barnett AH, Bailey CJ. SGLT inhibitors in management of diabetes. Lancet Diabetes Endocrinol 2013;1:140–51. https://doi.org/10.1016/S2213-8587(13)70050-0
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/jamacardio.2020.4511
Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2022;65:1925–66. https://doi.org/10.1007/s00125-022-05787-2
Day C, Bailey CJ. The hypocaloric diet in type 2 diabetes - déjà vu. Br J Diab Vasc Dis 2012;12:48-52. https://doi.org/10.1177/1474651412437503
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