New oral antidiabetics – pharmaceutical chemical characterization of sodium-glucose cotransporter-2 inhibitors

1 Wittmann I – Diabetológia jegyzet orvostanhallgatóknak, Pécsi Tudományegyetem, Pécs, 2020, 16-17. Search in Google Scholar

2 IDF Diabetes Atlas 2021– https://diabetesatlas.org/atlas/tenth-edition Search in Google Scholar

3 Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, Stein C, Basit A, Chan JC, Mbanya JC, Pavkov ME. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes research and clinical practice. 2022 Jan 1;183:109119. Search in Google Scholar

4 Opie LH. Sodium glucose co-transporter 2 (SGLT2) inhibi­tors: new among antidiabetic drugs. Cardiovascular drugs and therapy. 2014 Aug;28:331-4. Search in Google Scholar

5 Zhang Y, Liu ZP. Recent developments of C-aryl glucoside SGLT2 inhibitors. Current Medicinal Chemistry. 2016 Mar 1;23(8):832-49. Search in Google Scholar

6 Faillie JL. Pharmacological aspects of the safety of gliflozins. Pharmacological Research. 2017 Apr 1;118:71-81. Search in Google Scholar

7 Ramani J, Shah H, Vyas VK, Sharma M. A review on the medicinal chemistry of sodium glucose co-transporter 2 inhibitors (SGLT2-I): Update from 2010 to present. European Journal of Medicinal Chemistry Reports. 2022 Aug 2:100074. Search in Google Scholar

8 Mazákné Kraszni M. A nem-inzulin antidiabetikumok gyógyszerészi kémiája-II. rész. Search in Google Scholar

9 Manoj A, Das S, Kunnath Ramachandran A, Alex AT, Joseph A. SGLT2 inhibitors, an accomplished development in field of medicinal chemistry: an extensive review. Future Medicinal Chemistry. 2020 Nov;12(21):1961-90. Search in Google Scholar

10 Nakagaito M, Joho S, Ushijima R, Nakamura M, Kinugawa K. Comparison of canagliflozin, dapagliflozin and empagliflozin added to heart failure treatment in decompensated heart fail­ure patients with type 2 diabetes mellitus. Circulation reports. 2019 Oct 10;1(10):405-13. Search in Google Scholar

11 Aguillon AR, Mascarello A, Segretti ND, de Azevedo HF, Guimaraes CR, Miranda LS, de Souza RO. Synthetic strate­gies toward SGLT2 inhibitors. Organic Process Research & Development. 2018 Mar 30;22(4):467-88. Search in Google Scholar

12 Nickerson B, Salisbury JJ, Harwood JW. Enantioselective anal­ysis for L-pidolic acid in ertugliflozin drug substance and drug product by chiral gas chromatography with derivatization. Journal of Pharmaceutical and Biomedical Analysis. 2018 Sep 10; 159:212-6. Search in Google Scholar

13 https://go.drugbank.com/drugs/DB08907 Search in Google Scholar

14 https://go.drugbank.com/drugs/DB06292 Search in Google Scholar

15 https://go.drugbank.com/drugs/DB09038 Search in Google Scholar

16 https://go.drugbank.com/drugs/DB11827 Search in Google Scholar

17 https://go.drugbank.com/drugs/DB11698 Search in Google Scholar

18 https://go.drugbank.com/drugs/DB11824 Search in Google Scholar

19 https://go.drugbank.com/drugs/DB12214 Search in Google Scholar

20 https://go.drugbank.com/unearth/q?searcher=drugs&que­ry=sotegliflozin&button= Search in Google Scholar

21 https://go.drugbank.com/drugs/DB12236 Search in Google Scholar

22 https://go.drugbank.com/unearth/q?searcher=drugs&que­ry=remogliflozin&button= Search in Google Scholar

23 Fawzy MG, Hassan WE, Mostafa AA, Sayed RA. Different approaches for the assessment of greenness of spectropho­tometric methodologies utilized for resolving the spectral overlap of newly approved binary hypoglycemic pharmaceu­tical mixture. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2022 May 5;272:120998. Search in Google Scholar

24 Moussa BA, Mahrouse MA, Fawzy MG. Different resolution techniques for management of overlapped spectra: Application for the determination of novel co-formulated hypoglyce­mic drugs in their combined pharmaceutical dosage form. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2018 Dec 5;205:235-42. Search in Google Scholar

25 Anjali M, Shreshta M, Prasanna R, Shrisha T, Kumar MS. Method development and validation of ertugliflozin and sita­gliptin by using simultaneous equation method. Journal of Innovation in Pharmaceutical Sciences. 2019;3(1):22-8. Search in Google Scholar

26 Elnadi S, Abdalsabour S, Farouk M, Trabik YA. Fourier trans­form infrared spectroscopic, spectrofluorimetric assays of canagliflozin, and stability-indicating UV-spectrophotometric method for the simultaneous determination of canagliflozin and metformin. Journal of AOAC International. 2022 Jul 1;105(4):964-71. Search in Google Scholar

27 Azhakesan A, Kuppusamy S. Canagliflozin: A review with specific focus on analytical methods in biological matrices and pharmaceuticals. Reviews in Analytical Chemistry. 2022 Dec 2;41(1):287-300. Search in Google Scholar

28 Oh DW, Chon J, Kang JH, Han CS, Shin DH, Kim JY, Rhee YS, Chun MH, Kim DW, Park CW. Physicochemical characteriza­tion of dapagliflozin and its solid-state behavior in stress sta­bility test. Drug development and industrial pharmacy. 2021 May 4;47(5):685-93. Search in Google Scholar

29 Liu M, Liu J, Wang Q, Song P, Li H, Wu S, Gong J. Quantitative analysis of low content polymorphic impurities in cana­gliflozin tablets by PXRD, NIR, ATR-FITR and Raman sol­id-state analysis techniques combined with stoichiometry. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2023 May 15;293:122458. Search in Google Scholar

30 Oh DW, Chon J, Kang JH, Han CS, Shin DH, Kim JY, Rhee YS, Chun MH, Kim DW, Park CW. Physicochemical characteriza­tion of dapagliflozin and its solid-state behavior in stress sta­bility test. Drug development and industrial pharmacy. 2021 May 4;47(5):685-93. Search in Google Scholar

31 Abbas NS, Mohamed YA, Derayea SM, Omar MA, Saleh GA. Simple TLC–spectrodensitometric method for studying lipophilicity and quantitative analysis of hypoglycemic drugs in their binary mixture. Biomedical Chromatography. 2021 Nov;35(11):e5154. Search in Google Scholar

32 Itigimatha N, Chadchan KS, Yallur BC, Hadagali MD. Simple and sensitive RP-HPLC and UV spectroscopic methods for the determination of remogliflozin etabonate in pure and phar­maceutical formulations. Turkish Journal of Pharmaceutical Sciences. 2022 Apr;19(2):213. Search in Google Scholar

33 Elnadi S, Abdalsabour S, Abdalghany MF, Trabik YA. Stability indicating RP-HPLC and spectrophotometric methods for determination of gliflozins in their mixture with metformin. Journal of the Iranian Chemical Society. 2022 May;19(5):1723-35. Search in Google Scholar

34 Thakor NS, Amrutkar SV. A systematic review of Analytical profiles of SGLT2 inhibitors and their combinations for treat­ment of type 2 Diabetes Mellitus. Current Pharmaceutical Analysis. 2019 Dec 1;15(7):681-93. Search in Google Scholar

35 van der Aart-van der Beek AB, Wessels AMA, Heerspink HJL, Touw DJ – Simple, fast and robust LC-MS/MS method for the simultaneous quantification of canagliflozin, dapagliflozin and empagliflozin in human plasma and urine, Journal of Chromatography B, 2020, 1152:1. Search in Google Scholar

36 Ganorkar SB, Sharma SS, Patil MR, Bobade PS, Dhote AM, Shirkhedkar AA. Pharmaceutical analytical profile for novel SGL-2 inhibitor: dapagliflozin. Critical Reviews in Analytical Chemistry. 2021 Nov 17;51(8):835-47. Search in Google Scholar

37 Maher HM, Abdelrahman AE, Alzoman NZ, Aljohar HI. Stability-indicating capillary electrophoresis method for the simultaneous determination of metformin hydrochloride, saxagliptin hydrochloride, and dapagliflozin in pharmaceu­tical tablets. Journal of Liquid Chromatography & Related Technologies. 2019 Apr 3;42(5-6):161-71. Search in Google Scholar

38 Gumieniczek A, Berecka A. Analytical tools for determination of new oral antidiabetic drugs, glitazones, gliptins, gliflozins and glinides, in bulk materials, pharmaceuticals and biological samples. Open Chemistry. 2016 Jan 1;14(1):215-42.019 Apr 3;42(5-6):161-71. Search in Google Scholar

39 Frampton JE. Empagliflozin: a review in type 2 diabetes. Drugs. 2018 Jul;78:1037-48. Search in Google Scholar

40 Gonzalez DE, Foresto RD, Ribeiro AB. SGLT-2 inhibitors in diabetes: a focus on renoprotection. Revista da Associação Médica Brasileira. 2020 Jan 13;66:s17-24. Search in Google Scholar

41 Zhou Y, Fan J, Zheng C, Yin P, Wu H, Li X, Luo N, Yu X, Chen C. SGLT-2 inhibitors reduce glucose absorption from perito­neal dialysis solution by suppressing the activity of SGLT-2. Biomedicine & Pharmacotherapy. 2019 Jan 1;109:1327-38. Search in Google Scholar

42 Ramani J, Shah H, Vyas VK, Sharma M. A review on the medicinal chemistry of sodium glucose co-transporter 2 inhibitors (SGLT2-I): Update from 2010 to present. European Journal of Medicinal Chemistry Reports. 2022 Aug 2:100074. Search in Google Scholar

43 Winkler G. Vércukorcsökkentő kezelés felnőttkori diabetes­ben. Gyógyszerészet, 2014, 58:399-409. Search in Google Scholar

44 Winkler G, Jermendy Gy. Dapagliflozin, a nátri­um-glukóz kotranszporter-2 gátló vércukorcsökkentők első törzskönyvezett képviselője. Diabetologia Hungarica, 2013, 21(1):21-29. Search in Google Scholar

45 Vaduganathan M, Docherty KF, Claggett BL, Jhund PS, de Boer RA, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CS, Martinez F, Shah SJ. SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. The Lancet. 2022 Sep 3;400(10354):757-67. Search in Google Scholar

46 Tang H, Xu C, Zhang P, Luo T, Huang Y, Yang X. A Profile of SGLT-2 inhibitors in Hyponatremia: The Evidence to Date. European Journal of Pharmaceutical Sciences. 2023 Mar 2:106415. Search in Google Scholar

47 van der Aart-van AB, Wessels AM, Heerspink HJ, Touw DJ. Simple, fast and robust LC-MS/MS method for the simultane­ous quantification of canagliflozin, dapagliflozin and empagli­flozin in human plasma and urine. Journal of Chromatography B. 2020 Sep 1;1152:122257. Search in Google Scholar

48 Oliva RV, Bakris GL. Blood pressure effects of sodium–glucose co-transport 2 (SGLT2) inhibitors. Journal of the American Society of Hypertension. 2014 May 1;8(5):330-9. Search in Google Scholar

49 Packer M. SGLT2 inhibitors produce cardiorenal benefits by promoting adaptive cellular reprogramming to induce a state of fasting mimicry: a paradigm shift in understanding their mechanism of action. Diabetes Care. 2020 Mar 1;43(3):508-11. Search in Google Scholar

50 Koch B, Fuhrmann DC, Schubert R, Geiger H, Speer T, Baer PC. Gliflozins Have an Anti-Inflammatory Effect on Renal Proximal Tubular Epithelial Cells in a Diabetic and Inflammatory Microenvironment In Vitro. International Journal of Molecular Sciences. 2023 Jan 17;24(3):1811. Search in Google Scholar

51 Bendotti G, Montefusco L, Pastore I, Lazzaroni E, Lunati ME, Fiorina P. The anti-inflammatory and immunological properties of SGLT-2 inhibitors. Journal of Endocrinological Investigation. 2023 Dec;46(12):2445-52. Search in Google Scholar

52 Salvatore T, Caturano A, Galiero R, Di Martino A, Albanese G, Vetrano E, Sardu C, Marfella R, Rinaldi L, Sasso FC. Cardiovascular benefits from gliflozins: effects on endothelial function. Biomedicines. 2021 Sep 29;9(10):1356. Search in Google Scholar

53 Vallon V. Renoprotective Effects of SGLT2 Inhibitors. Heart Failure Clinics. 2022 Oct 1;18(4):539-49. Search in Google Scholar

54 Sukiatno L, Kusuma IY, Samodra G. Cardioprotective and Renoprotective Effects of the Use of SGLT2 Inhibitors in Diabetes Mellitus Patients. InInternational Conference on Health and Medical Sciences (AHMS 2020) 2021 Jan 27 (pp. 121-127). Atlantis Press. Search in Google Scholar

55 Ravindran S, Munusamy S. Renoprotective mechanisms of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors against the progression of diabetic kidney disease. Journal of cellular physiology. 2022 Feb;237(2):1182-205. Search in Google Scholar

56 Belančić A, Klobučar S. Sodium-Glucose Co-Transporter 2 Inhibitors as a Powerful Cardioprotective and Renoprotective Tool: Overview of Clinical Trials and Mechanisms. Diabetology. 2023 Jul 4;4(3):251-8. Search in Google Scholar

57 Kawasoe S, Maruguchi Y, Kajiya S, Uenomachi H, Miyata M, Kawasoe M, Kubozono T, Ohishi M. Mechanism of the blood pressure-lowering effect of sodium-glucose cotransporter 2 inhibitors in obese patients with type 2 diabetes. BMC Pharmacology and Toxicology. 2017 Dec;18:1-0 Search in Google Scholar

58 Billing AM, Kim YC, Gullaksen S, Schrage B, Raabe J, Hutzfeldt A, Demir F, Kovalenko E, Lassé M, Dugourd A, Fallegger R. Metabolic communication by SGLT2 inhibition. Circulation. 2023 Dec 28. Search in Google Scholar

59 Gumieniczek A, Berecka-Rycerz A. Metabolism and chem­ical degradation of new antidiabetic drugs: a review of ana­lytical approaches for analysis of glutides and gliflozins. Biomedicines. 2023 Jul 27;11(8):2127. Search in Google Scholar

60 Garcia-Ropero A, Badimon JJ, Santos-Gallego CG. The phar­macokinetics and pharmacodynamics of SGLT2 inhibitors for type 2 diabetes mellitus: the latest developments. Expert Opinion on Drug Metabolism & Toxicology. 2018 Dec 2;14(12):1287-302. Search in Google Scholar

61 Tirucherai GS, Lacreta F, Ismat FA, Tang W, Boulton DW. Pharmacokinetics and pharmacodynamics of dapagliflozin in children and adolescents with type 2 diabetes mellitus. Diabetes, Obesity and Metabolism. 2016 Jul;18(7):678-84. Search in Google Scholar

62 Devineni D, Polidori D. Clinical pharmacokinetic, pharmaco­dynamic, and drug–drug interaction profile of canagliflozin, a sodium-glucose co-transporter 2 inhibitor. Clinical pharma­cokinetics. 2015 Oct;54:1027-41. Search in Google Scholar

63 Kasichayanula S, Liu X, LaCreta F, Griffen SC, Boulton DW. Clinical pharmacokinetics and pharmacodynamics of dapagli­flozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clinical pharmacokinetics. 2014 Jan;53:17-27. Search in Google Scholar

64 Gumieniczek A, Berecka-Rycerz A. Metabolism and chem­ical degradation of new antidiabetic drugs: a review of ana­lytical approaches for analysis of glutides and gliflozins. Biomedicines. 2023 Jul 27;11(8):2127. Search in Google Scholar

65 Madaan T, Akhtar M, Najmi AK. Sodium glucose CoTransporter 2 (SGLT2) inhibitors: Current status and future perspective. European Journal of Pharmaceutical Sciences. 2016 Oct 10;93:244-52. Search in Google Scholar

66 Kaur P, Behera BS, Singh S, Munshi A. The pharmacological profile of SGLT2 inhibitors: Focus on mechanistic aspects and pharmacogenomics. European Journal of Pharmacology. 2021 Aug 5;904:174169. Search in Google Scholar

67 Donnier-Maréchal M, Vidal S. Glycogen phosphorylase inhibitors: a patent review (2013-2015). Expert opinion on therapeutic patents. 2016 Feb 1;26(2):199-212. Search in Google Scholar

68 Isaji M. SGLT2 inhibitors: molecular design and potential dif­ferences in effect. Kidney International. 2011 Mar 1;79: S14-9. Search in Google Scholar

69 Dharia A, Khan A, Sridhar VS, Cherney DZ. SGLT2 inhibitors: the sweet success for kidneys. Annual Review of Medicine. 2023 Jan 27;74:369-84. Search in Google Scholar

70 Eickhoff MK, Dekkers CC, Kramers BJ, Laverman GD, Frimodt-Møller M, Jørgensen NR, Faber J, Danser AJ, Gansevoort RT, Rossing P, Persson F. Effects of dapagliflozin on volume status when added to renin–angiotensin system inhibitors. Journal of clinical medicine. 2019 May 31;8(6):779. Search in Google Scholar

71 Caruso I, Giorgino F. SGLT-2 inhibitors as cardio-renal protective agents. Metabolism. 2022 Feb 1;127:154937. Search in Google Scholar

72 Palmer BF, Clegg DJ. Kidney-protective effects of SGLT2 inhibitors. Clinical Journal of the American Society of Nephrology. 2023 Feb 1;18(2):279-89. Search in Google Scholar

73 Frigy A, Germán-Salló M, Máthé L, Szabó M. Vércukorcsökkentő gyógyszerek biztonságossága szívelégtelenségben| The safety of anti-diabetic drugs in heart failure. Orvosi Hetilap. 2017;158(5):163-71. Search in Google Scholar

74 Meca AD, Tarțău LM, Popa EG, Gafițanu C, Crețeanu A, Bogdan M. Noi perspective asupra tratamentului cu antidiabetice orale, Farmacist Ro, 2019, 187(2):25-28 Search in Google Scholar

75 https://www.nps.org.au/radar/articles/sglt2-inhibitor-listings-indications-and-combinations Search in Google Scholar

76 Jafar TH. FDA approval of dapagliflozin for chronic kidney disease: a remarkable achievement?. The Lancet. 2021 Jul 24;398(10297):283-4. Search in Google Scholar

77 Agenda Medicală 2024, Editura Medicală, București, 2024. Search in Google Scholar

78 MemoMed Ediția 30 – Memorator de farmacologie, Editura Universitară, București, 2024. Search in Google Scholar

79 Confederat LG, Condurache MI, Alexa RE, Dragostin OM. Particularities of urinary tract infections in diabetic patients: a concise review. Medicina. 2023 Sep 29;59(10):1747. Search in Google Scholar

80 Update MD. SGLT2 inhibitors: reports of Fournier’s gangrene (necrotising fasciitis of the genitalia or perineum), 18 February 2019. Accessed online. 2021 May;6. Search in Google Scholar

81 Górriz JL, Navarro-González JF, Ortiz A, Vergara A, Nunez J, Jacobs-Cachá C, Martínez-Castelao A, Soler MJ. Sodium-glucose cotransporter 2 inhibition: towards an indication to treat diabetic kidney disease. Nephrology Dialysis Transplantation. 2020 Jan 1;35(Supplement_1):i13-23. Search in Google Scholar

82 Gu N, Park SI, Chung H, Jin X, Lee S, Kim TE. Possibility of pharmacokinetic drug interaction between a DPP-4 inhibitor and a SGLT2 inhibitor. Translational and Clinical Pharmacology. 2020 Mar;28(1):17. Search in Google Scholar