{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:18:57Z","timestamp":1791317937779,"version":"4.3.1"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2024,3,9]],"date-time":"2024-03-09T00:00:00Z","timestamp":1709942400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,3,9]],"date-time":"2024-03-09T00:00:00Z","timestamp":1709942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Drug Investig"],"published-print":{"date-parts":[[2024,4]]},"DOI":"10.1007\/s40261-024-01351-5","type":"journal-article","created":{"date-parts":[[2024,3,9]],"date-time":"2024-03-09T12:02:01Z","timestamp":1709985721000},"page":"223-250","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Should Glucokinase be Given a Chance in Diabetes Therapeutics? A Clinical-Pharmacological Review of Dorzagliatin and Lessons Learned So Far"],"prefix":"10.1007","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8147-4333","authenticated-orcid":false,"given":"Upinder","family":"Kaur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhairav Kumar","family":"Pathak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tharik Jalal","family":"Meerashahib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dondapati Venkata Vamshi","family":"Krishna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sankha Shubhra","family":"Chakrabarti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,9]]},"reference":[{"key":"1351_CR1","unstructured":"Diabetes. World Health Organization. https:\/\/www.who.int\/health-topics\/diabetes. Accessed 21 Feb 2024."},{"key":"1351_CR2","unstructured":"International Diabetes Federation. Facts and figures. https:\/\/idf.org\/about-diabetes\/facts-figures\/. Accessed 21 Feb 2024."},{"key":"1351_CR3","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s12933-022-01516-6","volume":"21","author":"C-X Ma","year":"2022","unstructured":"Ma C-X, Ma X-N, Guan C-H, Li Y-D, Mauricio D, Fu S-B. Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management. Cardiovasc Diabetol. 2022;21:74.","journal-title":"Cardiovasc Diabetol"},{"key":"1351_CR4","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/cen.12119","volume":"80","author":"P de Pablos-Velasco","year":"2014","unstructured":"de Pablos-Velasco P, Parhofer KG, Bradley C, Eschw\u00e8ge E, G\u00f6nder-Frederick L, Maheux P, et al. Current level of glycemic control and its associated factors in patients with type 2 diabetes across Europe: data from the PANORAMA study. Clin Endocrinol (Oxf). 2014;80:47\u201356.","journal-title":"Clin Endocrinol (Oxf)"},{"key":"1351_CR5","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1001\/jamainternmed.2019.2396","volume":"179","author":"P Kazemian","year":"2019","unstructured":"Kazemian P, Shebl FM, McCann N, Walensky RP, Wexler DJ. Evaluation of the cascade of diabetes care in the United States, 2005\u20132016. JAMA Intern Med. 2019;179:1376\u201385.","journal-title":"JAMA Intern Med"},{"key":"1351_CR6","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1007\/s11154-020-09545-w","volume":"21","author":"J Bar-Tana","year":"2020","unstructured":"Bar-Tana J. Type 2 diabetes: unmet need, unresolved pathogenesis, mTORC1-centric paradigm. Rev Endocr Metab Disord. 2020;21:613\u201329.","journal-title":"Rev Endocr Metab Disord"},{"key":"1351_CR7","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/S2213-8587(18)30315-2","volume":"7","author":"International Hypoglycemia Study Group","year":"2019","unstructured":"International Hypoglycemia Study Group. Hypoglycemia, cardiovascular disease, and mortality in diabetes: epidemiology, pathogenesis, and management. Lancet Diabetes Endocrinol. 2019;7:385\u201396.","journal-title":"Lancet Diabetes Endocrinol"},{"key":"1351_CR8","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.pcad.2017.09.001","volume":"60","author":"ME Herman","year":"2017","unstructured":"Herman ME, O\u2019Keefe JH, Bell DSH, Schwartz SS. Insulin therapy increases cardiovascular risk in type 2 diabetes. Prog Cardiovasc Dis. 2017;60:422\u201334.","journal-title":"Prog Cardiovasc Dis"},{"key":"1351_CR9","doi-asserted-by":"publisher","first-page":"663","DOI":"10.2337\/dc16-1972","volume":"40","author":"TL Middleton","year":"2017","unstructured":"Middleton TL, Wong J, Molyneaux L, Brooks BA, Yue DK, Twigg SM, et al. Cardiac effects of sulfonylurea-related hypoglycemia. Diabetes Care. 2017;40:663\u201370.","journal-title":"Diabetes Care"},{"key":"1351_CR10","unstructured":"US FDA. FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-revises-labels-sglt2-inhibitors-diabetes-include-warnings-about-too-much-acid-blood-and-serious. Accessed 21 Feb 2024."},{"key":"1351_CR11","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3390\/jcm12010145","volume":"12","author":"JJ Gorgojo-Mart\u00ednez","year":"2022","unstructured":"Gorgojo-Mart\u00ednez JJ, Mezquita-Raya P, Carretero-G\u00f3mez J, Castro A, Cebri\u00e1n-Cuenca A, de Torres-S\u00e1nchez A, et al. Clinical recommendations to manage gastrointestinal adverse events in patients treated with Glp-1 receptor agonists: a multidisciplinary expert consensus. J Clin Med. 2022;12:145.","journal-title":"J Clin Med"},{"key":"1351_CR12","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1016\/j.cmet.2018.03.001","volume":"27","author":"DJ Drucker","year":"2018","unstructured":"Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27:740\u201356.","journal-title":"Cell Metab"},{"key":"1351_CR13","first-page":"59","volume":"9","author":"S Uitrakul","year":"2022","unstructured":"Uitrakul S, Aksonnam K, Srivichai P, Wicheannarat S, Incomenoy S. The incidence and risk factors of urinary tract infection in patients with type 2 diabetes mellitus using SGLT2 inhibitors: a real-world observational study. Med Basel Switz. 2022;9:59.","journal-title":"Med Basel Switz"},{"key":"1351_CR14","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.910","volume":"10","author":"H Yang","year":"2022","unstructured":"Yang H, Choi E, Park E, Na E, Chung SY, Kim B, et al. Risk of genital and urinary tract infections associated with SGLT-2 inhibitors as an add-on therapy to metformin in patients with type 2 diabetes mellitus: a retrospective cohort study in Korea. Pharmacol Res Perspect. 2022;10: e00910.","journal-title":"Pharmacol Res Perspect"},{"key":"1351_CR15","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/s40265-020-01278-z","volume":"80","author":"KA Toulis","year":"2020","unstructured":"Toulis KA, Nirantharakumar K, Pourzitaki C, Barnett AH, Tahrani AA. Glucokinase activators for type 2 diabetes: challenges and future developments. Drugs. 2020;80:467\u201375.","journal-title":"Drugs"},{"key":"1351_CR16","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1111\/jdi.12294","volume":"6","author":"A Nakamura","year":"2015","unstructured":"Nakamura A, Terauchi Y. Present status of clinical deployment of glucokinase activators. J Diabetes Investig. 2015;6:124\u201332.","journal-title":"J Diabetes Investig"},{"key":"1351_CR17","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1080\/14756366.2021.2025362","volume":"37","author":"Y Ren","year":"2022","unstructured":"Ren Y, Li L, Wan L, Huang Y, Cao S. Glucokinase as an emerging anti-diabetes target and recent progress in the development of its agonists. J Enzym Inhib Med Chem. 2022;37:606\u201315.","journal-title":"J Enzym Inhib Med Chem"},{"key":"1351_CR18","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3389\/fphys.2019.00148","volume":"10","author":"FM Matschinsky","year":"2019","unstructured":"Matschinsky FM, Wilson DF. The central role of glucokinase in glucose homeostasis: a perspective 50\u00a0years after demonstrating the presence of the enzyme in islets of Langerhans. Front Physiol. 2019;10:148.","journal-title":"Front Physiol"},{"key":"1351_CR19","doi-asserted-by":"publisher","first-page":"G645","DOI":"10.1152\/ajpgi.00015.2016","volume":"310","author":"A Fournel","year":"2016","unstructured":"Fournel A, Marlin A, Abot A, Pasquio C, Cirillo C, Cani PD, et al. Glucosensing in the gastrointestinal tract: impact on glucose metabolism. Am J Physiol Gastrointest Liver Physiol. 2016;310:G645\u201358.","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"1351_CR20","doi-asserted-by":"publisher","first-page":"9002","DOI":"10.3390\/s101009002","volume":"10","author":"VH Routh","year":"2010","unstructured":"Routh VH. Glucose sensing neurons in the ventromedial hypothalamus. Sensors. 2010;10:9002\u201325.","journal-title":"Sensors"},{"key":"1351_CR21","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.cmet.2014.02.003","volume":"19","author":"CM Lamy","year":"2014","unstructured":"Lamy CM, Sanno H, Labou\u00e8be G, Picard A, Magnan C, Chatton J-Y, et al. Hypoglycemia-activated GLUT2 neurons of the nucleus tractus solitarius stimulate vagal activity and glucagon secretion. Cell Metab. 2014;19:527\u201338.","journal-title":"Cell Metab"},{"key":"1351_CR22","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.2337\/diabetes.51.9.2757","volume":"51","author":"F Reimann","year":"2002","unstructured":"Reimann F, Gribble FM. Glucose-sensing in glucagon-like peptide-1-secreting cells. Diabetes. 2002;51:2757\u201363.","journal-title":"Diabetes"},{"key":"1351_CR23","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1007\/s00125-008-1183-9","volume":"52","author":"R Murphy","year":"2009","unstructured":"Murphy R, Tura A, Clark PM, Holst JJ, Mari A, Hattersley AT. Glucokinase, the pancreatic glucose sensor, is not the gut glucose sensor. Diabetologia. 2009;52:154\u20139.","journal-title":"Diabetologia"},{"key":"1351_CR24","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1007\/s00125-012-2521-5","volume":"55","author":"A Nakamura","year":"2012","unstructured":"Nakamura A, Togashi Y, Orime K, Sato K, Shirakawa J, Ohsugi M, et al. Control of beta cell function and proliferation in mice stimulated by small-molecule glucokinase activator under various conditions. Diabetologia. 2012;55:1745\u201354.","journal-title":"Diabetologia"},{"key":"1351_CR25","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1172\/JCI17645","volume":"117","author":"Y Terauchi","year":"2007","unstructured":"Terauchi Y, Takamoto I, Kubota N, Matsui J, Suzuki R, Komeda K, et al. Glucokinase and IRS-2 are required for compensatory \u03b2 cell hyperplasia in response to high-fat diet-induced insulin resistance. J Clin Investig. 2007;117:246\u201357.","journal-title":"J Clin Investig"},{"key":"1351_CR26","doi-asserted-by":"publisher","first-page":"995","DOI":"10.33549\/physiolres.934487","volume":"69","author":"J Hul\u00edn","year":"2020","unstructured":"Hul\u00edn J, \u0160kopkov\u00e1 M, Valkovi\u010dov\u00e1 T, Mikulajov\u00e1 S, Roso\u013eankov\u00e1 M, Papcun P, et al. Clinical implications of the glucokinase impaired function: GCK MODY today. Physiol Res. 2020;69:995\u20131011.","journal-title":"Physiol Res"},{"key":"1351_CR27","first-page":"21","volume":"2021","author":"WJ Loh","year":"2021","unstructured":"Loh WJ, Dacay LM, Tan CSH, Ang SF, Yap F, Lim SC, et al. Glucokinase activating mutation causing hypoglycemia diagnosed late in adult who fasts for Ramadhan. Endocrinol Diabetes Metab Case Rep. 2021;2021:21\u20130043.","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"key":"1351_CR28","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1111\/cen.12517","volume":"81","author":"BG Challis","year":"2014","unstructured":"Challis BG, Harris J, Sleigh A, Isaac I, Orme SM, Seevaratnam N, et al. Familial adult onset hyperinsulinism due to an activating glucokinase mutation: implications for pharmacological glucokinase activation. Clin Endocrinol (Oxf). 2014;81:855\u201361.","journal-title":"Clin Endocrinol (Oxf)"},{"key":"1351_CR29","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.molmet.2014.12.007","volume":"4","author":"RA Haeusler","year":"2015","unstructured":"Haeusler RA, Camastra S, Astiarraga B, Nannipieri M, Anselmino M, Ferrannini E. Decreased expression of hepatic glucokinase in type 2 diabetes. Mol Metab. 2015;4:222\u20136.","journal-title":"Mol Metab"},{"key":"1351_CR30","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1055\/s-2007-979899","volume":"27","author":"JF Caro","year":"1995","unstructured":"Caro JF, Triester S, Patel VK, Tapscott EB, Frazier NL, Dohm GL. Liver glucokinase: decreased activity in patients with type II diabetes. Horm Metab Res. 1995;27:19\u201322.","journal-title":"Horm Metab Res"},{"key":"1351_CR31","doi-asserted-by":"publisher","first-page":"272","DOI":"10.2337\/diabetes.49.2.272","volume":"49","author":"A Basu","year":"2000","unstructured":"Basu A, Basu R, Shah P, Vella A, Johnson CM, Nair KS, et al. Effects of type 2 diabetes on the ability of insulin and glucose to regulate splanchnic and muscle glucose metabolism: evidence for a defect in hepatic glucokinase activity. Diabetes. 2000;49:272\u201383.","journal-title":"Diabetes"},{"key":"1351_CR32","doi-asserted-by":"publisher","first-page":"78","DOI":"10.2337\/db08-1119","volume":"58","author":"TP Torres","year":"2009","unstructured":"Torres TP, Catlin RL, Chan R, Fujimoto Y, Sasaki N, Printz RL, et al. Restoration of hepatic glucokinase expression corrects hepatic glucose flux and normalizes plasma glucose in Zucker diabetic fatty rats. Diabetes. 2009;58:78\u201386.","journal-title":"Diabetes"},{"key":"1351_CR33","doi-asserted-by":"publisher","first-page":"R1381","DOI":"10.1152\/ajpregu.00260.2006","volume":"292","author":"J-S Shin","year":"2007","unstructured":"Shin J-S, Torres TP, Catlin RL, Donahue EP, Shiota M. A defect in glucose-induced dissociation of glucokinase from the regulatory protein in Zucker diabetic fatty rats in the early stage of diabetes. Am J Physiol Regul Integr Comp Physiol. 2007;292:R1381\u201390.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"1351_CR34","doi-asserted-by":"publisher","first-page":"622","DOI":"10.2337\/diabetes.50.3.622","volume":"50","author":"M Shiota","year":"2001","unstructured":"Shiota M, Postic C, Fujimoto Y, Jetton TL, Dixon K, Pan D, et al. Glucokinase gene locus transgenic mice are resistant to the development of obesity-induced type 2 diabetes. Diabetes. 2001;50:622\u20139.","journal-title":"Diabetes"},{"key":"1351_CR35","doi-asserted-by":"publisher","first-page":"2022","DOI":"10.2337\/diabetes.48.10.2022","volume":"48","author":"RM O\u2019Doherty","year":"1999","unstructured":"O\u2019Doherty RM, Lehman DL, T\u00e9l\u00e9maque-Potts S, Newgard CB. Metabolic impact of glucokinase overexpression in liver: lowering of blood glucose in fed rats is accompanied by hyperlipidemia. Diabetes. 1999;48:2022\u20137.","journal-title":"Diabetes"},{"key":"1351_CR36","doi-asserted-by":"publisher","first-page":"E1126","DOI":"10.1210\/jc.2010-2017","volume":"96","author":"A Peter","year":"2011","unstructured":"Peter A, Stefan N, Cegan A, Walenta M, Wagner S, K\u00f6nigsrainer A, et al. Hepatic glucokinase expression is associated with lipogenesis and fatty liver in humans. J Clin Endocrinol Metab. 2011;96:E1126\u201330.","journal-title":"J Clin Endocrinol Metab"},{"key":"1351_CR37","doi-asserted-by":"publisher","first-page":"3112","DOI":"10.2337\/db08-0516","volume":"57","author":"M Orho-Melander","year":"2008","unstructured":"Orho-Melander M, Melander O, Guiducci C, Perez-Martinez P, Corella D, Roos C, et al. Common missense variant in the glucokinase regulatory protein gene is associated with increased plasma triglyceride and C-reactive protein but lower fasting glucose concentrations. Diabetes. 2008;57:3112\u201321.","journal-title":"Diabetes"},{"key":"1351_CR38","doi-asserted-by":"publisher","first-page":"4081","DOI":"10.1093\/hmg\/ddp357","volume":"18","author":"NL Beer","year":"2009","unstructured":"Beer NL, Tribble ND, McCulloch LJ, Roos C, Johnson PRV, Orho-Melander M, et al. The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver. Hum Mol Genet. 2009;18:4081\u20138.","journal-title":"Hum Mol Genet"},{"key":"1351_CR39","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1007\/s00125-011-2348-5","volume":"55","author":"MG Rees","year":"2012","unstructured":"Rees MG, Wincovitch S, Schultz J, Waterstradt R, Beer NL, Baltrusch S, et al. Cellular characterisation of the GCKR P446L variant associated with type 2 diabetes risk. Diabetologia. 2012;55:114\u201322.","journal-title":"Diabetologia"},{"key":"1351_CR40","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/ng.521","volume":"42","author":"R Saxena","year":"2010","unstructured":"Saxena R, Hivert M-F, Langenberg C, Tanaka T, Pankow JS, Vollenweider P, et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010;42:142\u20138.","journal-title":"Nat Genet"},{"key":"1351_CR41","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1007\/s00125-003-1244-z","volume":"46","author":"T Ferre","year":"2003","unstructured":"Ferre T, Riu E, Franckhauser S, Agudo J, Bosch F. Long-term overexpression of glucokinase in the liver of transgenic mice leads to insulin resistance. Diabetologia. 2003;46:1662\u20138.","journal-title":"Diabetologia"},{"key":"1351_CR42","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.2337\/dc11-1200","volume":"34","author":"GE Meininger","year":"2011","unstructured":"Meininger GE, Scott R, Alba M, Shentu Y, Luo E, Amin H, et al. Effects of MK-0941, a novel glucokinase activator, on glycemic control in insulin-treated patients with type 2 diabetes. Diabetes Care. 2011;34:2560\u20136.","journal-title":"Diabetes Care"},{"key":"1351_CR43","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1111\/dom.12586","volume":"18","author":"L Katz","year":"2016","unstructured":"Katz L, Manamley N, Snyder WJ, Dodds M, Agafonova N, Sierra-Johnson J, et al. AMG 151 (ARRY-403), a novel glucokinase activator, decreases fasting and postprandial glycemia in patients with type 2 diabetes. Diabetes Obes Metab. 2016;18:191\u20135.","journal-title":"Diabetes Obes Metab"},{"key":"1351_CR44","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1111\/dom.12088","volume":"15","author":"JPH Wilding","year":"2013","unstructured":"Wilding JPH, Leonsson-Zachrisson M, Wessman C, Johnsson E. Dose-ranging study with the glucokinase activator AZD1656 in patients with type 2 diabetes mellitus on metformin. Diabetes Obes Metab. 2013;15:750\u20139.","journal-title":"Diabetes Obes Metab"},{"key":"1351_CR45","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1007\/s40261-020-00971-x","volume":"40","author":"S Zheng","year":"2020","unstructured":"Zheng S, Shao F, Ding Y, Fu Z, Fu Q, Ding S, et al. Safety, pharmacokinetics, and pharmacodynamics of globalagliatin, a glucokinase activator, in Chinese patients with type 2 diabetes mellitus: a randomized, phase Ib, 28-day ascending dose study. Clin Drug Investig. 2020;40:1155\u201366.","journal-title":"Clin Drug Investig"},{"key":"1351_CR46","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1111\/dom.12474","volume":"17","author":"NB Amin","year":"2015","unstructured":"Amin NB, Aggarwal N, Pall D, Paragh G, Denney WS, Le V, et al. Two dose-ranging studies with PF-04937319, a systemic partial activator of glucokinase, as add-on therapy to metformin in adults with type 2 diabetes. Diabetes Obes Metab. 2015;17:751\u20139.","journal-title":"Diabetes Obes Metab"},{"key":"1351_CR47","doi-asserted-by":"publisher","first-page":"5028","DOI":"10.1210\/jc.2010-1041","volume":"95","author":"RC Bonadonna","year":"2010","unstructured":"Bonadonna RC, Heise T, Arbet-Engels C, Kapitza C, Avogaro A, Grimsby J, et al. Piragliatin (RO4389620), a novel glucokinase activator, lowers plasma glucose both in the postabsorptive state and after a glucose challenge in patients with type 2 diabetes mellitus: a mechanistic study. J Clin Endocrinol Metab. 2010;95:5028\u201336.","journal-title":"J Clin Endocrinol Metab"},{"key":"1351_CR48","doi-asserted-by":"publisher","first-page":"5163","DOI":"10.1172\/JCI129057","volume":"129","author":"M Drabkin","year":"2019","unstructured":"Drabkin M, Yogev Y, Zeller L, Zarivach R, Zalk R, Halperin D, et al. Hyperuricemia and gout caused by missense mutation in d-lactate dehydrogenase. J Clin Invest. 2019;129:5163\u20138.","journal-title":"J Clin Invest"},{"key":"1351_CR49","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1038\/ng.2500","volume":"45","author":"A K\u00f6ttgen","year":"2013","unstructured":"K\u00f6ttgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J, Hundertmark C, et al. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013;45:145\u201354.","journal-title":"Nat Genet"},{"key":"1351_CR50","doi-asserted-by":"crossref","unstructured":"Litwack G. Chapter 6\u2014Insulin and sugars. In: Litwack G, editor. Hum Biochem. Boston: Academic Press; 2018. pp. 131\u201360. https:\/\/www.sciencedirect.com\/science\/article\/pii\/B9780123838643000065. Accessed 19 Aug 2023.","DOI":"10.1016\/B978-0-12-383864-3.00006-5"},{"key":"1351_CR51","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1136\/annrheumdis-2014-206074","volume":"75","author":"Y Wang","year":"2016","unstructured":"Wang Y, Viollet B, Terkeltaub R, Liu-Bryan R. AMP-activated protein kinase suppresses urate crystal-induced inflammation and transduces colchicine effects in macrophages. Ann Rheum Dis. 2016;75:286\u201394.","journal-title":"Ann Rheum Dis"},{"key":"1351_CR52","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1038\/s41591-022-01803-5","volume":"28","author":"W Yang","year":"2022","unstructured":"Yang W, Zhu D, Gan S, Dong X, Su J, Li W, et al. Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial. Nat Med. 2022;28:974\u201381.","journal-title":"Nat Med"},{"key":"1351_CR53","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1038\/s41591-022-01802-6","volume":"28","author":"D Zhu","year":"2022","unstructured":"Zhu D, Li X, Ma J, Zeng J, Gan S, Dong X, et al. Dorzagliatin in drug-na\u00efve patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial. Nat Med. 2022;28:965\u201373.","journal-title":"Nat Med"},{"key":"1351_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2022.110118","volume":"193","author":"K Wang","year":"2022","unstructured":"Wang K, Shi M, Yang A, Fan B, Tam CHT, Lau E, et al. GCKR and GCK polymorphisms are associated with increased risk of end-stage kidney disease in Chinese patients with type 2 diabetes: the Hong Kong Diabetes Register (1995\u20132019). Diabetes Res Clin Pract. 2022;193: 110118.","journal-title":"Diabetes Res Clin Pract"},{"key":"1351_CR55","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1155\/2013\/215407","volume":"35","author":"J Lian","year":"2013","unstructured":"Lian J, Guo J, Chen Z, Jiang Q, Ye H, Huang X, et al. Positive association between GCKR rs780093 polymorphism and coronary heart disease in the aged Han Chinese. Dis Markers. 2013;35:863\u20138.","journal-title":"Dis Markers"},{"key":"1351_CR56","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13098-021-00637-4","volume":"13","author":"AS Zahedi","year":"2021","unstructured":"Zahedi AS, Akbarzadeh M, Sedaghati-Khayat B, Seyedhamzehzadeh A, Daneshpour MS. GCKR common functional polymorphisms are associated with metabolic syndrome and its components: a 10-year retrospective cohort study in Iranian adults. Diabetol Metab Syndr. 2021;13:20.","journal-title":"Diabetol Metab Syndr"},{"key":"1351_CR57","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/S2213-8587(18)30105-0","volume":"6","author":"D Zhu","year":"2018","unstructured":"Zhu D, Gan S, Liu Y, Ma J, Dong X, Song W, et al. Dorzagliatin monotherapy in Chinese patients with type 2 diabetes: a dose-ranging, randomised, double-blind, placebo-controlled, phase 2 study. Lancet Diabetes Endocrinol. 2018;6:627\u201336.","journal-title":"Lancet Diabetes Endocrinol"},{"key":"1351_CR58","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1111\/dom.13338","volume":"20","author":"X-X Zhu","year":"2018","unstructured":"Zhu X-X, Zhu D-L, Li X-Y, Li Y-L, Jin X-W, Hu T-X, et al. Dorzagliatin (HMS5552), a novel dual-acting glucokinase activator, improves glycemic control and pancreatic \u03b2-cell function in patients with type 2 diabetes: a 28-day treatment study using biomarker-guided patient selection. Diabetes Obes Metab. 2018;20:2113\u201320.","journal-title":"Diabetes Obes Metab"},{"key":"1351_CR59","doi-asserted-by":"publisher","first-page":"299","DOI":"10.2337\/db22-0708","volume":"72","author":"E Chow","year":"2023","unstructured":"Chow E, Wang K, Lim CKP, Tsoi STF, Fan B, Poon E, et al. Dorzagliatin, a dual-acting glucokinase activator, increases insulin secretion and glucose sensitivity in glucokinase maturity-onset diabetes of the young and recent-onset type 2 diabetes. Diabetes. 2023;72:299\u2013308.","journal-title":"Diabetes"},{"key":"1351_CR60","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1038\/s41467-023-36946-7","volume":"14","author":"L Chen","year":"2023","unstructured":"Chen L, Zhang J, Sun Y, Zhao Y, Liu X, Fang Z, et al. A phase I open-label clinical trial to study drug-drug interactions of dorzagliatin and sitagliptin in patients with type 2 diabetes and obesity. Nat Commun. 2023;14:1405.","journal-title":"Nat Commun"},{"key":"1351_CR61","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050215","volume":"5","author":"A Rosengren","year":"2008","unstructured":"Rosengren A, Jing X, Eliasson L, Renstr\u00f6m E. Why treatment fails in type 2 diabetes. PLoS Med. 2008;5: e215.","journal-title":"PLoS Med"},{"key":"1351_CR62","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/s41574-023-00815-6","volume":"19","author":"O Tysoe","year":"2023","unstructured":"Tysoe O. Sulfonylurea secondary failure mechanism identified. Nat Rev Endocrinol. 2023;19:189\u2013189.","journal-title":"Nat Rev Endocrinol"},{"key":"1351_CR63","first-page":"1619","volume":"10","author":"H Xu","year":"2016","unstructured":"Xu H, Sheng L, Chen W, Yuan F, Yang M, Li H, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of novel glucokinase activator HMS5552: results from a first-in-human single ascending dose study. Drug Des Dev Ther. 2016;10:1619\u201326.","journal-title":"Drug Des Dev Ther"},{"key":"1351_CR64","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1111\/cts.13174","volume":"15","author":"J Miao","year":"2022","unstructured":"Miao J, Fu P, Ren S, Hu C, Wang Y, Jiao C, et al. Effect of renal impairment on the pharmacokinetics and safety of dorzagliatin, a novel dual-acting glucokinase activator. Clin Transl Sci. 2022;15:548\u201357.","journal-title":"Clin Transl Sci"},{"key":"1351_CR65","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1111\/dom.12100","volume":"15","author":"A Kiyosue","year":"2013","unstructured":"Kiyosue A, Hayashi N, Komori H, Leonsson-Zachrisson M, Johnsson E. Dose-ranging study with the glucokinase activator AZD1656 as monotherapy in Japanese patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2013;15:923\u201330.","journal-title":"Diabetes Obes Metab"},{"key":"1351_CR66","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.diabres.2012.09.025","volume":"98","author":"H Ericsson","year":"2012","unstructured":"Ericsson H, Sj\u00f6berg F, Heijer M, Dorani H, Johansson P, Wollbratt M, et al. The glucokinase activator AZD6370 decreases fasting and postprandial glucose in type 2 diabetes mellitus patients with effects influenced by dosing regimen and food. Diabetes Res Clin Pract. 2012;98:436\u201344.","journal-title":"Diabetes Res Clin Pract"},{"key":"1351_CR67","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1002\/cpdd.261","volume":"5","author":"WS Denney","year":"2016","unstructured":"Denney WS, Denham DS, Riggs MR, Amin NB. Glycemic effect and safety of a systemic, partial glucokinase activator, PF-04937319, in patients with type 2 diabetes mellitus inadequately controlled on metformin: a randomized, crossover, active-controlled study. Clin Pharmacol Drug Dev. 2016;5:517\u201327.","journal-title":"Clin Pharmacol Drug Dev"},{"key":"1351_CR68","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.101185","volume":"42","author":"D Liu","year":"2021","unstructured":"Liu D, Du Y, Yao X, Wei Y, Zhu J, Cui C, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of the glucokinase activator PB-201 and its effects on the glucose excursion profile in drug-na\u00efve Chinese patients with type 2 diabetes: a randomised controlled, crossover, single-centre phase 1 trial. EClinicalMedicine. 2021;42: 101185.","journal-title":"EClinicalMedicine"},{"key":"1351_CR69","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1002\/jcph.589","volume":"56","author":"J Zhi","year":"2016","unstructured":"Zhi J, Zhai S. Effects of piragliatin, a glucokinase activator, on fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus. J Clin Pharmacol. 2016;56:231\u20138.","journal-title":"J Clin Pharmacol"},{"key":"1351_CR70","doi-asserted-by":"publisher","first-page":"eaau3441","DOI":"10.1126\/scitranslmed.aau3441","volume":"11","author":"A Vella","year":"2019","unstructured":"Vella A, Freeman JLR, Dunn I, Keller K, Buse JB, Valcarce C. Targeting hepatic glucokinase to treat diabetes with TTP399, a hepatoselective glucokinase activator. Sci Transl Med. 2019;11:eaau3441.","journal-title":"Sci Transl Med"},{"key":"1351_CR71","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000027476","volume":"100","author":"Q Gao","year":"2021","unstructured":"Gao Q, Zhang W, Li T, Yang G, Zhu W, Chen N, et al. The efficacy and safety of glucokinase activators for the treatment of type-2 diabetes mellitus. Medicine (Baltim). 2021;100: e27476.","journal-title":"Medicine (Baltim)"},{"key":"1351_CR72","unstructured":"A 12-week, phase 2, randomized, double-blind, placebo controlled, dose-ranging, parallel group study to evaluate the efficacy and safety of once daily Pf-04991532 and sitagliptin in adult patients with type 2 diabetes mellitus inadequately controlled on metformin. ClinicalTrials.gov; 2013 Jun. Report No.: NCT01336738. Pfizer. https:\/\/clinicaltrials.gov\/study\/NCT01336738. Accessed 21 Feb 2024."},{"key":"1351_CR73","unstructured":"Safety and tolerability of multiple ascending doses of LY2608204 in patients with type 2 diabetes mellitus. ClinicalTrials.gov; 2018 Oct. Report No.: NCT01247363. Eli Lilly and Company. https:\/\/clinicaltrials.gov\/study\/NCT01247363. Accessed 21 Feb 2024."},{"key":"1351_CR74","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0172252","volume":"12","author":"Y Tsumura","year":"2017","unstructured":"Tsumura Y, Tsushima Y, Tamura A, Hasebe M, Kanou M, Kato H, et al. TMG-123, a novel glucokinase activator, exerts durable effects on hyperglycemia without increasing triglyceride in diabetic animal models. PLoS ONE. 2017;12: e0172252.","journal-title":"PLoS ONE"},{"key":"1351_CR75","doi-asserted-by":"publisher","first-page":"960","DOI":"10.2337\/dc20-2684","volume":"44","author":"KR Klein","year":"2021","unstructured":"Klein KR, Freeman JLR, Dunn I, Dvergsten C, Kirkman MS, Buse JB, et al. The SimpliciT1 study: a randomized, double-blind, placebo-controlled phase 1b\/2 adaptive study of TTP399, a hepatoselective glucokinase activator, for adjunctive treatment of type 1 diabetes. Diabetes Care. 2021;44:960\u20138.","journal-title":"Diabetes Care"},{"key":"1351_CR76","unstructured":"A study of LY2599506 in patients with type 2 diabetes. https:\/\/clinicaltrials.gov\/study\/NCT01024244. Accessed 7 Mar 2023."},{"key":"1351_CR77","unstructured":"A study of LY2599506 (Oral Agent Medication: Glucokinase Activator 1) in type 2 diabetes mellitus. https:\/\/clinicaltrials.gov\/study\/NCT01029795. Accessed 7 Mar 2023."},{"key":"1351_CR78","unstructured":"A study to compare two forms of LY2608204 in healthy people. https:\/\/clinicaltrials.gov\/study\/NCT01313286. Accessed 7 Mar 2023."}],"container-title":["Clinical Drug Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40261-024-01351-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40261-024-01351-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40261-024-01351-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T02:19:19Z","timestamp":1711765159000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40261-024-01351-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,9]]},"references-count":78,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["1351"],"URL":"https:\/\/doi.org\/10.1007\/s40261-024-01351-5","relation":{},"ISSN":["1173-2563","1179-1918"],"issn-type":[{"value":"1173-2563","type":"print"},{"value":"1179-1918","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,9]]},"assertion":[{"value":"22 February 2024","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2024","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No funding was received to write this review.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Upinder Kaur, Bhairav Kumar Pathak, Tharik Jalal Meerashahib, Dondapati Venkata Vamshi Krishna, and Sankha Shubhra Chakrabarti have no conflicts of interest that are directly relevant to the content of this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"Not applicable as the review did not involve any human or animal experiments.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"Not applicable. The article reviews data from other published papers, which are available in the public domain.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of Data and Material"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}},{"value":"UK: planned the study, supervised the data extraction, verified the extracted data, performed the literature search, and wrote the first draft of the paper. BKP: performed the literature search, assisted in writing the paper and the presentation of data, and verified the extracted data. TJM: assisted in writing the paper and the tabular presentation of data, and verified the extracted data. DVVK: contributed to the tabular presentation of data and verification of the extracted data. SSC: edited the final draft of the paper and performed the literature search.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 Contributions"}}]}}