Advances in SGLT2 Inhibitors for Type 2 Diabetes Management
Mohd. Javed Naim 1*
Journal of Angiotherapy 8(10) 1-13 https://doi.org/10.25163/angiotherapy.8109951
Submitted: 11 June 2024 Revised: 05 October 2024 Published: 08 October 2024
Abstract
Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have emerged as a significant class of medications for the management of type 2 diabetes mellitus, offering improved glycemic control and cardiovascular benefits. This review focuses on the development of various SGLT2 inhibitors, highlighting their chemical structures, pharmacological properties, and therapeutic potential. Methods: A comprehensive literature review was conducted, summarizing the synthesis and biological evaluation of multiple SGLT2 inhibitors, including novel compounds derived from C-aryl glucoside scaffolds, C-glucosides, and 5α-carba-β-D-glucopyranose derivatives. Studies utilized various techniques, such as click chemistry, Friedel-Crafts alkylation, and pharmacokinetic assessments, to evaluate the efficacy and selectivity of these inhibitors. Results: Several promising compounds were identified, including compound 1 (GCC5694A) with an IC50 of 0.460 nM against SGLT2 and strong selectivity for SGLT1, and compound 26, which exhibited an IC50 of 4.47 nM, surpassing dapagliflozin. Novel derivatives, such as compound 22 (IC50 = 47 nM) and compound 27, demonstrated significant inhibitory effects and selectivity profiles. Pharmacokinetic studies revealed compounds like compound 28 had enhanced half-lives compared to established drugs like sergliflozin. Additionally, compounds such as the nitric oxide-releasing dapagliflozin derivative exhibited dual anti-diabetic and anti-thrombotic properties. Conclusion: The ongoing development of SGLT2 inhibitors demonstrates substantial advancements in therapeutic options for type 2 diabetes. The structural modifications and novel compounds explored in this review highlight the potential for improved efficacy and safety profiles, suggesting that these new agents could play a vital role in diabetes management and warrant further clinical investigation.
Keywords: SGLT2 inhibitors, pharmacokinetics, glucose metabolism, drug development, diabetes therapy
References
Abdul-Ghani, M. A., & DeFronzo, R. A. (2008). Inhibition of renal glucose reabsorption: a novel strategy for achieving glucose control in type 2 diabetes mellitus. Endocrine Practice, 14(6), 782-790.
Abdul-Ghani, M. A., Norton, L., & DeFronzo, R. A. (2015). Renal sodium-glucose cotransporter inhibition in the management of type 2 diabetes mellitus. American Journal of Physiology-Renal Physiology, 309(11), F889-F900.
Alvarado, F., & Crane, R. K. (1962). Phlorizin as a competitive inhibitor of the active transport of sugars by hamster small intestine, in vitro. Biochimica et biophysica acta, 56, 170-172.
Aylsworth, A., Dean, Z., VanNorman, C., & Nkemdirim Okere, A. (2014). Dapagliflozin for the treatment of type 2 diabetes mellitus. Annals of Pharmacotherapy, 48(9), 1202-1208.
Bailey, C. J., Day, C., & Bellary, S. (2022). Renal protection with SGLT2 inhibitors: effects in acute and chronic kidney disease. Current diabetes reports, 22(1), 39-52.
Bhattacharya, S., Rathore, A., Parwani, D., Mallick, C., Asati, V., Agarwal, S., Rajoriya, V., Das, R., & Kashaw, S. K. (2020). An exhaustive perspective on structural insights of SGLT2 inhibitors: A novel class of antidiabetic agent. European Journal of Medicinal Chemistry, 204, 112523.
Bhosle, D., Indurkar, S., Quadri, U., & Chandekar, B. (2022). A Comparative Study of efficacy and safety of different Sodium Glucose Co-transporter 2 (SGLT-2) Inhibitors in the Management of Patients with Type II Diabetes Mellitus. The Journal of the Association of Physicians of India, 70(6), 11-12.
Bonora, B. M., Avogaro, A., & Fadini, G. P. (2020). Extraglycemic effects of SGLT2 inhibitors: a review of the evidence. Diabetes, Metabolic Syndrome and Obesity, 161-174.
Chao, E. C., & Henry, R. R. (2010). SGLT2 inhibition—a novel strategy for diabetes treatment. Nature reviews drug discovery, 9(7), 551-559.
Chen, Z. H., Wang, R. W., & Qing, F. L. (2012). Synthesis and biological evaluation of SGLT2 inhibitors: gem-difluoromethylenated Dapagliflozin analogs. Tetrahedron Letters, 53(17), 2171-2176.
Chu, K. F., Song, J. S., Chen, C. T., Yeh, T. K., Hsieh, T. C., Huang, C. Y., Wang, M.H., Wu, S.H., Yao, C.H., Chao, Y.S., & Lee, J. C. (2019). Synthesis and biological evaluation of N-glucosyl indole derivatives as sodium-dependent glucose co-transporter 2 inhibitors. Bioorganic chemistry, 83, 520-525.
Davies, M. J., Aroda, V. R., Collins, B. S., Gabbay, R. A., Green, J., Maruthur, N. M., ... & Buse, J. B. (2022). Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care, 45(11), 2753-2786.
DeFronzo RA, Norton L, Abdul-Ghani M. Renal, metabolic and cardiovascular considerations of SGLT2 inhibition. Nature Reviews Nephrology. 2017 Jan;13(1):11-26.
DeFronzo, R. A., Davidson, J. A., & Del Prato, S. (2012). The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes, Obesity and Metabolism, 14(1), 5-14.
Dhillon, S. (2019). Dapagliflozin: a review in type 2 diabetes. Drugs, 79(10), 1135-1146.
Douros, A., Lix, L. M., Fralick, M., Dell'Aniello, S., Shah, B. R., Ronksley, P. E., ... & Canadian Network for Observational Drug Effect Studies (CNODES) Investigators*. (2020). Sodium–glucose cotransporter-2 inhibitors and the risk for diabetic ketoacidosis: a multicenter cohort study. Annals of internal medicine, 173(6), 417-425.
Ehrenkranz, J. R., Lewis, N. G., Ronald Kahn, C., & Roth, J. (2005). Phlorizin: a review. Diabetes/metabolism research and reviews, 21(1), 31-38.
Engelhardt, K., Ferguson, M., & Rosselli, J. L. (2021). Prevention and management of genital mycotic infections in the setting of sodium-glucose cotransporter 2 inhibitors. Annals of Pharmacotherapy, 55(4), 543-548.
Ferrannini, E., & Solini, A. (2012). SGLT2 inhibition in diabetes mellitus: rationale and clinical prospects. Nature Reviews Endocrinology, 8(8), 495-502.
Frampton, J. E. (2018). Empagliflozin: a review in type 2 diabetes. Drugs, 78, 1037-1048.
Garcia-Ropero, A., Badimon, J. J., & Santos-Gallego, C. G. (2018). The pharmacokinetics and pharmacodynamics of SGLT2 inhibitors for type 2 diabetes mellitus: the latest developments. Expert opinion on drug metabolism & toxicology, 14(12), 1287-1302.
Geerlings, S., Fonseca, V., Castro-Diaz, D., List, J., & Parikh, S. (2014). Genital and urinary tract infections in diabetes: impact of pharmacologically-induced glucosuria. Diabetes research and clinical practice, 103(3), 373-381.
Guo, C., Hu, M., DeOrazio, R. J., Usyatinsky, A., Fitzpatrick, K., Zhang, Z., ... & Liu, S. (2014). The design and synthesis of novel SGLT2 inhibitors: C-glycosides with benzyltriazolopyridinone and phenylhydantoin as the aglycone moieties. Bioorganic & medicinal chemistry, 22(13), 3414-3422.
Haering, H. U., Merker, L., Christiansen, A. V., Roux, F., Salsali, A., Kim, G., ... & Broedl, U. C. (2015). Empagliflozin as add-on to metformin plus sulphonylurea in patients with type 2 diabetes. Diabetes research and clinical practice, 110(1), 82-90.
Haider, K., Pathak, A., Rohilla, A., Haider, M. R., Ahmad, K., & Yar, M. S. (2019). Synthetic strategy and SAR studies of C-glucoside heteroaryls as SGLT2 inhibitor: A review. European journal of medicinal chemistry, 184, 111773.
Handlon, A. L. (2005). Sodium glucose co-transporter 2 (SGLT2) inhibitors as potential antidiabetic agents. Expert Opinion on Therapeutic Patents, 15(11), 1531-1540.
Ikegai, K., Imamura, M., Suzuki, T., Nakanishi, K., Murakami, T., Kurosaki, E., Noda, A., Kobayashi, Y., Yokota, M., Koide, T., Kosakai, K. (2013). Synthesis and biological evaluation of C-glucosides with azulene ring as selective SGLT2 inhibitors for the treatment of type 2 diabetes mellitus: Discovery of YM543. Bioorganic & medicinal chemistry, 21(13), 3934-3948.
Imran, H., Nester, W., Elgendy, I. Y., & Saad, M. (2020). Role of sodium glucose co-transporter 2 inhibitors in patients with heart failure: an elusive mechanism. Annals of Medicine, 52(5), 178-190.
Inzucchi, S. E., Zinman, B., Wanner, C., Ferrari, R., Fitchett, D., Hantel, S., Espadero, R. M., Woerle, H. J., Broedl, U. C., & Johansen, O. E. (2015). SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials. Diabetes and vascular disease Research, 12(2), 90-100.
Israr, A. L. I., Kumar, R., Barman, D. C., Nath, A., & Prasad, M. (2017). U.S. Patent Application No. 15/532,555.
Jabbour, S. A. (2009). The importance of reducing hyperglycemia while preserving insulin secretion—the rationale for sodium-coupled glucose co-transporter 2 inhibition in diabete. US Endocrinol, 5, 75-78.
Jakher, H., Chang, T. I., Tan, M., & Mahaffey, K. W. (2019). Canagliflozin review–safety and efficacy profile in patients with T2DM. Diabetes, metabolic syndrome and obesity: targets and therapy, 209-215.
Januzzi Jr, J. L., Butler, J., Jarolim, P., Sattar, N., Vijapurkar, U., Desai, M., & Davies, M. J. (2017). Effects of canagliflozin on cardiovascular biomarkers in older adults with type 2 diabetes. Journal of the American College of Cardiology, 70(6), 704-712.
Kang, S. Y., Song, K. S., Lee, J., Lee, S. H., & Lee, J. (2010). Synthesis of pyridazine and thiazole analogs as SGLT2 inhibitors. Bioorganic & medicinal chemistry, 18(16), 6069-6079.
Kanwal, A., & Banerjee, S. K. (2013). SGLT inhibitors: a novel target for diabetes. Pharmaceutical patent analyst, 2(1), 77-91.
Karumanchi, K., Natarajan, S. K., Chavakula, R., Korupolu, R. B., Bonige, K. B., & Peruri, B. G. (2020). Synthesis of metabolites of dapagliflozin: an SGLT2 inhibitor. Journal of Chemical Sciences, 132, 1-8.
Katsuno, K., Fujimori, Y., Takemura, Y., Hiratochi, M., Itoh, F., Komatsu, Y., Fujikura, H., & Isaji, M. (2007). Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal glucose reabsorption and modulates plasma glucose level. Journal of Pharmacology and Experimental Therapeutics, 320(1), 323-330.
Keller, D. M., & Lotspeich, W. D. (1959). Effect of phlorizin on the osmotic behavior of mitochondria in isotonic sucrose. Journal of Biological Chemistry, 234(4), 991-994.
Kim, M. J., Lee, S. H., Park, S. O., Kang, H., Lee, J. S., Lee, K. N., Jung, M. E., Kim, J., & Lee, J. (2011). Novel macrocyclic C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents. Bioorganic & medicinal chemistry, 19(18), 5468-5479.
Komatsu, S., Nomiyama, T., Numata, T., Kawanami, T., Hamaguchi, Y., Iwaya, C., Horikawa, T., Fujimura-Tanaka, Y., Hamanoue, N., Motonaga, R., Tanabe, M. (2020). SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation. Endocrine journal, 67(1), 99-106.
Kong, Y. K., Song, K. S., Jung, M. E., Kang, M., Kim, H. J., & Kim, M. J. (2022). Discovery of GCC5694A: A potent and selective sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes. Bioorganic & Medicinal Chemistry Letters, 56, 128466.
Kovacich, N., & Chavez, B. (2018). Ertugliflozin (steglatro): a new option for SGLT2 inhibition. Pharmacy and Therapeutics, 43(12), 736.
Kuo, G. H., Gaul, M. D., Liang, Y., Xu, J. Z., Du, F., Hornby, P., Xu, G., Qi, J., Wallace, N., Lee, S., & Demarest, K. (2018). Synthesis and biological evaluation of benzocyclobutane-C-glycosides as potent and orally active SGLT1/SGLT2 dual inhibitors. Bioorganic & Medicinal Chemistry Letters, 28(7), 1182-1187.
Lansdell, M. I., Burring, D. J., Hepworth, D., Strawbridge, M., Graham, E., Guyot, T., Betson, M. S., & Hart, J. D. (2008). Design and synthesis of fluorescent SGLT2 inhibitors. Bioorganic & medicinal chemistry letters, 18(18), 4944-4947.
Larmour, K., & Levin, A. (2021). Slowing progression in CKD: DAPA CKD and beyond. Clinical Journal of the American Society of Nephrology, 16(7), 1117-1119.
Lee, S. H., Song, K. S., Kim, J. Y., Kang, M., Lee, J. S., Cho, S. H., Park, H.J., Kim, J., & Lee, J. (2011). Novel thiophenyl C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents. Bioorganic & medicinal chemistry, 19(19), 5813-5832.
Lee, W. S., Kanai, Y., Wells, R. G., & Hediger, M. A. (1994). The high affinity Na+/glucose cotransporter. Re-evaluation of function and distribution of expression. Journal of Biological Chemistry, 269(16), 12032-12039.
Li, L. T., Zhou, L. F., Li, Y. J., Huang, J., Liu, R. H., Wang, B., & Wang, P. (2012). Facile synthesis of 1, 2, 3-triazole analogs of SGLT2 inhibitors by ‘click chemistry’. Bioorganic & medicinal chemistry letters, 22(1), 642-644.
Li, Z., Xu, X., Deng, L., Liao, R., Liang, R., Zhang, B., & Zhang, L. (2018). Design, synthesis and biological evaluation of nitric oxide releasing derivatives of dapagliflozin as potential anti-diabetic and anti-thrombotic agents. Bioorganic & Medicinal Chemistry, 26(14), 3947-3952.
Lin, H. W., & Tseng, C. H. (2014). A review on the relationship between SGLT2 inhibitors and cancer. International journal of endocrinology, 2014(1), 719578.
Lin, T. S., Liw, Y. W., Song, J. S., Hsieh, T. C., Yeh, H. W., Hsu, L. C., Lin, C. J., Wu, S. H., & Liang, P. H. (2013). Synthesis and biological evaluation of novel C-aryl d-glucofuranosides as sodium-dependent glucose co-transporter 2 inhibitors. Bioorganic & medicinal chemistry, 21(21), 6282-6291.
Maksud, N., Bera, S., Naim, M. J., & Alam, O. (2024). DAPAGLIFLOZIN: A NEW HOPE FOR THE THERAPEUTIC TREATMENT OF TYPE 2 DIABETES MELLITUS. European Journal of Medicinal Chemistry Reports, 100167.
Marrs, J. C., & Anderson, S. L. (2020). Ertugliflozin in the treatment of type 2 diabetes mellitus. Drugs in Context, 9.
Mazidi, M., Rezaie, P., Gao, H. K., & Kengne, A. P. (2017). Effect of sodium-glucose cotransport-2 inhibitors on blood pressure in people with type 2 diabetes mellitus: a systematic review and meta-analysis of 43 randomized control trials with 22528 patients. Journal of the American Heart Association, 6(6), e004007.
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., & Washburn, W. N. (2008). Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. Journal of medicinal chemistry, 51(5), 1145-1149.
Mukkamala, R., Kumar, R., Banerjee, S. K., & Aidhen, I. S. (2020). Synthesis of Benzyl C-Analogues of Dapagliflozin as Potential SGLT2 Inhibitors. European Journal of Organic Chemistry, 2020(12), 1828-1839.
Murakata, M., Kawase, A., Kimura, N., Ikeda, T., Nagase, M., Koizumi, M., ... & Shimizu, H. (2019). Synthesis of tofogliflozin as an SGLT2 inhibitor via construction of dihydroisobenzofuran by intramolecular [4+ 2] cycloaddition. Organic Process Research & Development, 23(4), 548-557.
Neal, B., Perkovic, V., Mahaffey, K. W., De Zeeuw, D., Fulcher, G., Erondu, N., ... & Matthews, D. R. (2017). Canagliflozin and cardiovascular and renal events in type 2 diabetes. New England Journal of Medicine, 377(7), 644-657.
Neeland, I. J., McGuire, D. K., Chilton, R., Crowe, S., Lund, S. S., Woerle, H. J., Broedl, U.C., & Johansen, O. E. (2016). Empagliflozin reduces body weight and indices of adipose distribution in patients with type 2 diabetes mellitus. Diabetes and Vascular Disease Research, 13(2), 119-126.
Neeland, I. J., Salahuddin, U., & McGuire, D. K. (2016). A safety evaluation of empagliflozin for the treatment of type 2 diabetes. Expert opinion on drug safety, 15(3), 393-402.
Nespoux, J., & Vallon, V. (2020). Renal effects of SGLT2 inhibitors: an update. Current opinion in nephrology and hypertension, 29(2), 190-198.
Ng, W. L., & Shing, T. K. (2018). Synthetic and biological studies of carbasugar SGLT2 inhibitors. Journal of Synthetic Organic Chemistry, Japan, 76(11), 1215-1222.
Ohtake, Y., Sato, T., Matsuoka, H., Nishimoto, M., Taka, N., Takano, K., Yamamoto, K., Ohmori, M., Higuchi, T., Murakata, M., & Kobayashi T. (2011). 5a-Carba-β-d-glucopyranose derivatives as novel sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes. Bioorganic & medicinal chemistry, 19(18), 5334-5341.
Oku, A., Ueta, K., Arakawa, K., Ishihara, T., Nawano, M., Kuronuma, Y., Matsumoto, M., Saito, A., Tsujihara, K., Anai, M., & Endou, H. (1999). T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes, 48(9), 1794-1800.
Pan, X., Huan, Y., Shen, Z., & Liu, Z. (2016). Synthesis and biological evaluation of novel tetrahydroisoquinoline-C-aryl glucosides as SGLT2 inhibitors for the treatment of type 2 diabetes. European Journal of Medicinal Chemistry, 114, 89-100.
Pinto, L. C., Rados, D. V., Remonti, L. R., Kramer, C. K., Leitao, C. B., & Gross, J. L. (2015). Efficacy of SGLT2 inhibitors in glycemic control, weight loss and blood pressure reduction: a systematic review and meta-analysis. Diabetology & metabolic syndrome, 7(1), 1-2.
Plosker, G. L. (2014). Canagliflozin: a review of its use in patients with type 2 diabetes mellitus. Drugs, 74, 807-824.
Polidori, D., Mari, A., & Ferrannini, E. (2014). Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves model-based indices of beta cell function in patients with type 2 diabetes. Diabetologia, 57, 891-901.
Rieg, T., Masuda, T., Gerasimova, M., Mayoux, E., Platt, K., Powell, D. R., Thomson, S. C., Koepsell, H., & Vallon, V. (2014). Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia. American Journal of Physiology-Renal Physiology, 306(2), F188-F193.
Rossetti, L., Smith, D., Shulman, G. I., Papachristou, D., & DeFronzo, R. A. (1987). Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. The Journal of clinical investigation, 79(5), 1510-1515.
Saeed, M. A., & Narendran, P. (2014). Dapagliflozin for the treatment of type 2 diabetes: a review of the literature. Drug design, development and therapy, 2493-2505.
Sattar, N., McLaren, J., Kristensen, S. L., Preiss, D., & McMurray, J. J. (2016). SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms?. Diabetologia, 59, 1333-1339.
Schaeffer, S. E., DesLauriers, C., Spiller, H. A., Aleguas, A., Baeza, S., & Ryan, M. L. (2018). Retrospective review of SGLT2 inhibitor exposures reported to 13 poison centers. Clinical toxicology, 56(3), 204-208.
Scheen, A. J. (2014). Evaluating SGLT2 inhibitors for type 2 diabetes: pharmacokinetic and toxicological considerations. Expert Opinion on Drug Metabolism & Toxicology, 10(5), 647-663.
Scheen, A. J. (2015). Pharmacodynamics, efficacy and safety of sodium–glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs, 75, 33-59.
Scheen, A. J. (2019). An update on the safety of SGLT2 inhibitors. Expert opinion on drug safety, 18(4), 295-311.
Scheen, A. J., & Paquot, N. (2014). Metabolic effects of SGLT-2 inhibitors beyond increased glucosuria: a review of the clinical evidence. Diabetes & metabolism, 40(6), S4-S11.
Scheen, A., & Deeks, E. (2017). Canagliflozin: A Review in Type 2 Diabetes. Drugs, 77(14).
Schwaiger, E., Burghart, L., Signorini, L., Ristl, R., Kopecky, C., Tura, A., ... & Hecking, M. (2019). Empagliflozin in posttransplantation diabetes mellitus: a prospective, interventional pilot study on glucose metabolism, fluid volume, and patient safety. American Journal of Transplantation, 19(3), 907-919.
Singh, M., & Kumar, A. (2018). Risks associated with SGLT2 inhibitors: an overview. Current drug safety, 13(2), 84-91.
Song, K. S., Lee, S. H., Kim, M. J., Seo, H. J., Lee, J., Lee, S. H., Jung, M. E., Son, E. J., Lee, M., Kim, J., & Lee, J. (2011). Synthesis and SAR of thiazolylmethylphenyl glucoside as novel C-aryl glucoside SGLT2 inhibitors. ACS Medicinal Chemistry Letters, 2(2), 182-187.
Thomas, M. C., & Cherney, D. Z. (2018). The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure. Diabetologia, 61, 2098-2107.
Turk, E., Zabel, B., Mundlos, S., Dyer, J., & Wright, E. M. (1991). Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. Nature, 350(6316), 354-356.
Vallon, V. (2015). The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus. Annual review of medicine, 66(1), 255-270.
Vallon, V., & Verma, S. (2021). Effects of SGLT2 inhibitors on kidney and cardiovascular function. Annual review of physiology, 83(1), 503-528.
Wang, Y., Lou, Y., Wang, J., Li, D., Chen, H., Zheng, T., Xia, C., Song, X., Dong, T., Li, J., & Liu, H. (2019). Design, synthesis and biological evaluation of 6-deoxy O-spiroketal C-arylglucosides as novel renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes. European journal of medicinal chemistry, 180, 398-416.
Watts, N. B., Bilezikian, J. P., Usiskin, K., Edwards, R., Desai, M., Law, G., & Meininger, G. (2016). Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. The Journal of Clinical Endocrinology, 101(1), 157-166.
White Jr, J. R. (2015). Empagliflozin, an SGLT2 inhibitor for the treatment of type 2 diabetes mellitus: a review of the evidence. Annals of Pharmacotherapy, 49(5), 582-598.
Wright, E. M. (2021). SGLT2 inhibitors: physiology and pharmacology. Kidney360, 2(12), 2027-2037.
Yabe, D., Hamamoto, Y., Seino, Y., Kuwata, H., Kurose, T., & Seino, Y. (2017). Sodium glucose co-transporter 2 inhibitor luseogliflozin in the management of type 2 diabetes: a drug safety evaluation. Expert Opinion on Drug Safety, 16(10), 1211-1218.
Yan, Q., Ding, N., & Li, Y. (2016). Synthesis and biological evaluation of novel dioxa-bicycle C-aryl glucosides as SGLT2 inhibitors. Carbohydrate Research, 421, 1-8.
Yang, F., Meng, R., & Zhu, D. L. (2020). Cardiovascular effects and mechanisms of sodium-glucose cotransporter-2 inhibitors. Chronic diseases and translational medicine, 6(04), 239-245.
Yang, X. Q., Xu, C., Sun, Y., & Han, R. F. (2013). Diabetes mellitus increases the risk of bladder cancer: an updated meta-analysis. Asian Pacific Journal of Cancer Prevention, 14(4), 2583-2589.
Yao, C. H., Song, J. S., Chen, C. T., Yeh, T. K., Hsieh, T. C., Wu, S. H., Huang, C. Y., Huang, Y.L., Wang, M. H., Liu, Y.W., & Tsai, C.H. (2012). Synthesis and biological evaluation of novel C-indolylxylosides as sodium-dependent glucose co-transporter 2 inhibitors. European journal of medicinal chemistry, 55, 32-38.
Yau, K., Dharia, A., Alrowiyti, I., & Cherney, D. Z. (2022). Prescribing SGLT2 inhibitors in patients with CKD: expanding indications and practical considerations. Kidney international reports, 7(7), 1463-1476.
Zhang, S., Wang, Y. L., Wei, Q. C., Xu, W. R., Tang, L. D., Zhao, G. L., & Wang, J. W. (2013). Design, synthesis and biological activity of cyclohexane-bearing C-glucoside derivatives as SGLT2 inhibitors. Chinese Chemical Letters, 24(5), 429-432.
Zhao, J. Z., Weinhandl, E. D., Carlson, A. M., & Peter, W. L. S. (2022). Hypoglycemia risk with SGLT2 inhibitors or glucagon-like peptide 1 receptor agonists versus sulfonylureas among medicare insured adults with CKD in the United States. Kidney Medicine, 4(8), 100510.
Zhao, W. J., Shi, Y. H., Zhao, G. L., Wang, Y. L., Shao, H., Da Tang, L., & Wang, J. W. (2011). Design, synthesis and in vivo anti-hyperglycemic activity of gem-dimethyl-bearing C-glucosides as SGLT2 inhibitors. Chinese Chemical Letters, 22(10), 1215-1218.
Zhao, X., Sun, B., Zheng, H., Liu, J., Qian, L., Wang, X., & Lou, H. (2018). Synthesis and biological evaluation of 6-hydroxyl C-aryl glucoside derivatives as novel sodium glucose co-transporter 2 (SGLT2) inhibitors. Bioorganic & Medicinal Chemistry Letters, 28(12), 2201-2205.
Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J. &, Broedl UC. (2015). Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. New england journal of medicine, 373(22), 2117-2128.
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