Development of SGLT1 and SGLT2 inhibitors
Open accessAbstract
Sodium-glucose cotransporters SGLT1 (encoded by SGLT1, also known as SLC5A1) and SGLT2 (encoded by SGLT2, also known as SLC5A2) are important mediators of epithelial glucose transport. While SGLT1 accounts for most of the dietary glucose uptake in the intestine, SGLT2 is responsible for the majority of glucose reuptake in the tubular system of the kidney, with SGLT1 reabsorbing the remainder of the filtered glucose. As a consequence, mutations in the SLC5A1 gene cause glucose/galactose malabsorption, whereas mutations in SLC5A2 are associated with glucosuria. Since the cloning of SGLT1 more than 30 years ago, big strides have been made in our understanding of these transporters and their suitability as drug targets. Phlorizin, a naturally occurring competitive inhibitor of SGLT1 and SGLT2, provided the first insights into potential efficacy, but its use was hampered by intestinal side effects and a short half-life. Nevertheless, it was a starting point for the development of specific inhibitors of SGLT1 and SGLT2, as well as dual SGLT1/2 inhibitors. Since the approval of the first SGLT2 inhibitor in 2013 by the US Food and Drug Administration, SGLT2 inhibitors have become a new mainstay in the treatment of type 2 diabetes mellitus. They also have beneficial effects on the cardiovascular system (including heart failure) and the kidney. This review focuses on the rationale for the development of individual SGLT2 and SGLT1 inhibitors, as well as dual SGLT1/2 inhibition, including, but not limited to, aspects of genetics, genetically modified mouse models, mathematical modelling and general considerations of drug discovery in the field of metabolism.
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For type 2 diabetes, complementary disease-modifying therapies may reduce or eliminate the need for insulin administration.
“For type 2 diabetes, complementary disease-modifying therapies that may reduce or eliminate the need for insulin administration have also represented a rapidly expanding field of interest130–132.”
From 100 years of insulin: celebrating the past, present and future of diabetes therapy (2021) · cites this paper as [131]
The Introduction describes SGLT inhibitors as glucose-lowering treatments for type 2 diabetes, and ‘Why target glucose handling in the kidney?’ reports cardiovascular and renal benefits. Neither passage says these therapies reduce or eliminate the need for insulin administration; the Perspectives section discusses adding inhibitors to insulin in type 1 diabetes instead. The claimed effect on insulin use in type 2 diabetes is therefore unsupported. (LLM, conf=0.84)
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Youssef, M. E., Yahya, G., Popoviciu, M. S., Cavalu, S. D., Abdel-Dayem, M. A., & Saber, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076039 · Cited by 71 · see citing works
“SGLT1 is primarily expressed in the small intestine, where it plays a crucial role in the absorption of glucose from the gut lumen [6].”
BackgroundWright, E. M. (2020) · Pflügers Archiv: European Journal of Physiology · doi:10.1007/s00424-020-02448-4 · Cited by 70 · see citing works
Bae, J. H. (2025) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2025.0220 · Cited by 72 · see citing works
“This inhibition reduces reabsorption of filtered glucose and sodium, promoting glycosuria and natriuresis [26].”
Wu, W., Zhang, Z.-H., Jing, D., Huang, X., Ren, D., Shao, Z.-W., & Zhang, Z.-C. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04980-w · Cited by 67 · see citing works
“SGLT2 (sodium-glucose cotransporter 2) is an important mediator of epithelial glucose transport and belongs to the SLC5A (solute carrier family 5) gene family [7].”
BackgroundZaibi, N., Li, P.-Y., & Xu, S.-Z. (2021) · PLoS ONE · doi:10.1371/journal.pone.0247234 · Cited by 66 · see citing works
“Dapagliflozin blocks sodium glucose co-transporter 2 (SGLT-2) encoded by SLC5A2 gene and thus inhibits the reabsorption of filtered glucose and sodium [4,5].”
BackgroundGlucose Metabolism in Acute Kidney Injury and Kidney Repair
Wen, L., Li, Y., Li, S., Hu, X., Wei, Q., & Dong, Z. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.744122 · Cited by 64 · see citing works
Inhibition of sodium-glucose cotransporter 2 suppresses renal stone formation.
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“Gliflozins act as SGLT2 inhibitors by causing glucose urinary excretion in the proximal tubules, decreasing hyperglycemia and body weight [188–191].”
BackgroundRole of TRPC6 in Progression of Diabetic Kidney Disease
Staruschenko, A., Spires, D. R., & Palygin, O. (2019) · Current Hypertension Reports · doi:10.1007/s11906-019-0960-9 · Cited by 65 · see citing works
Mechanisms and Evidence for Heart Failure Benefits from SGLT2 Inhibitors
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Central role of cardiac fibroblasts in myocardial fibrosis of diabetic cardiomyopathy
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Glucose Metabolism in the Kidney: Neurohormonal Activation and Heart Failure Development
Gronda, E., Jessup, M. L., Iacoviello, M., Palazzuoli, A., & Claudio Napoli, A. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.120.018889 · Cited by 81 · see citing works
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: Benefits Versus Risk
Jasleen, B., Vishal, G., Sameera, M., Fahad, M., Brendan, O., Deion, S., & Pemminati, S. (2023) · Cureus · doi:10.7759/cureus.33939 · Cited by 51 · see citing works
“In 2013, the first sodiumglucose cotransporter 2 SGLT2 inhibitor (SGLT2i), canagliflozin, was released after Food and Drug Administration (FDA) approval, followed by a cascade of similar "flozins" within the next several years [2].”
BackgroundGonzález, C. D., Negueruela, M. P. C., Santamarina, C. N., Resnik, R., & Vaccaro, M. I. (2021) · Cells · doi:10.3390/cells10092497 · Cited by 60 · see citing works
“Another transporter, SGLT1, acts on the other 10% [93].”
BackgroundSodium-glucose cotransporter 2 inhibitors: extending the indication to non-diabetic kidney disease?
Dekkers, C. C. J., & Gansevoort, R. T. (2019) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfz264 · Cited by 57 · see citing works
Progression of diabetic kidney disease in T2DN rats
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SGLT2 Inhibitors in Chronic Kidney Disease: From Mechanisms to Clinical Practice
Škrabić, R., Kumrić, M., Vrdoljak, J., Rušić, D., Skrabic, I., Vilović, M., Martinović, D., Duplancic, V., Kurir, T. T., & Božić, J. (2022) · Biomedicines · doi:10.3390/biomedicines10102458 · Cited by 51 · see citing works
“Consequently, the valve opens at a lower threshold, and subsequently more glucose is excreted with urine [21].”
BackgroundXu, J., Hirai, T., Koya, D., & Kitada, M. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm11010137 · Cited by 53 · see citing works
“These structures are resistant to hydrolysis by β-glucosidases to increase their half-life and specificity to SGLT2 [27,28].”
BackgroundMoradi-Marjaneh, R., Paseban, M., & Sahebkar, A. (2019) · Phytotherapy Research · doi:10.1002/ptr.6421 · Cited by 47 · see citing works
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“27 This causes a significant osmotic diuresis and natriuresis with the reduction in plasma volume 28 and a mild drop of blood pressure, 29 resulting in mitigation of structural remodeling of the atrium.”
BackgroundPhenotypic profiling of solute carriers characterizes serine transport in cancer
Papalazarou, V., Newman, A. C., Huerta-Uribe, A., Legrave, N. M., Falcone, M., Zhang, T., Mcgarry, L., Athineos, D., Shanks, E., Blyth, K., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00936-2 · Cited by 45 · see citing works
Toxic mechanisms of the trichothecenes T-2 toxin and deoxynivalenol on protein synthesis.
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Mechanisms of SGLT2 Inhibitors in Heart Failure and Their Clinical Value
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“Sodium-glucose cotransporter 2 (SGLT2) inhibitors inhibit proximal tubular glucose reabsorption, leading to glycosuria [3].”
BackgroundThe Extraglycemic Effect of SGLT-2is on Mineral and Bone Metabolism and Bone Fracture
Dong, B., Lv, R., Wang, J., Che, L., Wang, Z.-C., Huai, Z., Wang, Y.-G., & Xu, L.-L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.918350 · Cited by 42 · see citing works
“SGLT-1 accounts for most of the dietary glucose uptake by the intestinal tract and the transmembrane transport of glucose and galactose through the brush margin of the small intestine, while SGLT-2 is responsible for the majority of glucose reuptake in the tubular system of the kidney (6).”
BackgroundSGLT2 inhibitors: a focus on cardiac benefits and potential mechanisms
Muric, M. D., Zivkovic, V. I., Joksimović, J., Sretenovic, J. Z., Davidović, G., Simovic, S. M., Djoković, D., Muric, N. N., Bolevich, S., & Jakovljevic, V. L. (2021) · Heart Failure Reviews · doi:10.1007/s10741-021-10079-9 · Cited by 44 · see citing works
Synthetic strategy and SAR studies of C-glucoside heteroaryls as SGLT2 inhibitor: A review.
Haider, K., Pathak, A., Rohilla, A., Haider, M., Ahmad, K., & Yar, M. S. (2019) · European journal of medicinal chemistry · doi:10.1016/j.ejmech.2019.111773 · Cited by 41 · see citing works
The anti-diabetic potential of betaine. Mechanisms of action in rodent models of type 2 diabetes.
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“However, inhibiting global glucose transport would be challenging, as healthy cells require the function of GLUT family transporters to maintain normal biological activity [1,2].”
BackgroundInfluentialSGLT2 inhibition effect on salt-induced hypertension, RAAS, and Na+ transport in Dahl SS rats
Kravtsova, O., Bohovyk, R., Levchenko, V., Palygin, O., Klemens, C. A., Rieg, T., & Staruschenko, A. (2022) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00053.2022 · Cited by 54 · see citing works
Self-citationPhloretin inhibits Zika virus infection by interfering with cellular glucose utilisation.
Lin, S.-C., Chen, M.-C., Liu, S.-F., Callahan, V., Bracci, N. R., Lehman, C., Dahal, B., de la Fuente, C. L., Lin, C.-C., Wang, T. T., et al. (2019) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2019.03.017 · Cited by 38 · see citing works
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“Sodium-dependent glucose transporters (SGLTs) can actively transport glucose against a concentration gradient [16].”
BackgroundUpdate of Indoles: Promising molecules for ameliorating metabolic diseases.
Hu, W., Yan, G., Ding, Q., Cai, J.-P., Zhang, Z.-Y., Zhao, Z., Lei, H., & Zhu, Y.-Z. (2022) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2022.112957 · Cited by 37 · see citing works
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“Sodium‐glucose cotransporter (SGLT) inhibitors, including selective SGLT2 inhibitors and dual SGLT1/2 inhibitors, are a novel class of oral antidiabetic drugs that lower blood glucose via an insulin‐independent mechanism.(1,2) SGLT inhibitors were expected to be a potential promising adjunct therapy to insulin in type…”
BackgroundDapagliflozin delays renal fibrosis in diabetic kidney disease by inhibiting YAP/TAZ activation.
Feng, L., Chen, Y., Li, N., Yang, X.-J., Zhou, L., Li, H.-R., Wang, T.-T., Xie, M., & Liu, H.-B. (2023) · Life Science · doi:10.1016/j.lfs.2023.121671 · Cited by 36 · see citing works
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Muscoli, S., Barillà, F., Tajmir, R., Meloni, M., Della‐Morte, D., Bellia, A., Daniele, N. D., Lauro, D., & Andreadi, A. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14081730 · Cited by 39 · see citing works
“The SGLT2 activity requires energy provided by the gradient generated by the Na+/K+ ATPase at the basolateral surface of the PCT epithelial cells, in contrast to the passive transport of glucose from the cytoplasm to plasma via GLUT2 [15].”
BackgroundSGLT2 inhibitors and AMPK: The road to cellular housekeeping?
Safaie, N., Masoumi, S., Alizadeh, S., Mirzajanzadeh, P., Nejabati, H., Hajiabbasi, M., Alivirdiloo, V., Basmenji, N. C., Radvar, A. D., Majidi, Z., et al. (2024) · Cell Biochemistry and Function · doi:10.1002/cbf.3922 · Cited by 33 · see citing works
“79 Despite the benefits of simultaneous inhibition of intestinal SGLT1 and renal SGLT2, there is a potential for bloating, gastro-intestinal (GI) discomfort, and diarrhea afterward the malabsorption of intestinal glucose/galactose.”
BackgroundThe role of autophagy in the treatment of type II diabetes and its complications: a review
Zhao, X., Bie, L., Pang, D.-R., Li, X., Yang, L., Chen, D., Wang, Y.-R., & Gao, Y. J. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1228045 · Cited by 38 · see citing works
“The sodium-dependent glucose transporters 2 (SGLT2) located in the proximal tubule are responsible for reabsorbing 90% of the glucose that is fi ltered through the glomerulus (105).”
BackgroundZügner, E., Yang, H., Kotzbeck, P., Boulgaropoulos, B., Sourij, H., Hagvall, S., Elmore, C. S., ESTERLINE, R. L., Moosmang, S., Oscarsson, J., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147966 · Cited by 33 · see citing works
“SGLT2 is responsible for the majority of glucose reuptake in the tubular system of the kidneys [19], and selective SGLT2 inhibitors act by blocking the SGLT2-mediated reabsorption of glucose and sodium in the proximal tubule of the kidneys [26].”
BackgroundFleming, N., Hamblin, P., Story, D., & Ekinci, E. (2020) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/clinem/dgaa200 · Cited by 32 · see citing works
Liu, H., Ertay, A., Peng, P., Li, J., Liu, D., Xiong, H., Zou, Y., Qiu, H., Hancock, D. C., Yuan, X., et al. (2019) · Molecular Oncology · doi:10.1002/1878-0261.12530 · Cited by 37 · see citing works
“…regulate EGFR activity in TNBC. Sodium/glucose cotransporter 1, encoded by the SLC5A1 gene in humans, is an active glucose transporter, which utilizes sodium gradients to transport glucose into cells independent of extracellular glucose concentration (Rieg and Vallon, 2018; Wright et al., 2011).”
BackgroundCurrent, emerging, and potential therapies for non-alcoholic steatohepatitis
Yang, Z. L., & Wang, L. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1152042 · Cited by 26 · see citing works
“Sodium–glucose cotransporter-2 (SGLT-2) has been reported as a critical mediator of epithelial glucose transport in charge of the majority of glucose reuptake in the kidney (Rieg and Vallon, 2018).”
BackgroundZeng, S., Delić, D., Chu, C., Xiong, Y., Luo, T., Chen, X.-Y., Gaballa, M. M. S., Xue, Y., Chen, X., Cao, Y., et al. (2021) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2021.112606 · Cited by 31 · see citing works
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Genovese, M., Nesi, I., Caselli, A., & Paoli, P. (2021) · Molecules · doi:10.3390/molecules26164818 · Cited by 35 · see citing works
“As a precautionary measure, it could be of great importance to evaluate the ability of these molecules to inhibit the activity of intestinal glucose transporters in order to avoid the risk of inducing a hypoglycemic condition [70].”
BackgroundShan, X., Wang, X., Jiang, H., Cai, C., Hao, J., & Yu, G. (2020) · Marine Drugs · doi:10.3390/md18090485 · Cited by 30 · see citing works
Liang, I.-C., Chang, H.-H., Lai, Y.-J., Chan, C.-M., Sung, C.-H., Pu, C., Chang, D., Ho, C.-C., & Hung, C. (2025) · Medicina · doi:10.3390/medicina61020202 · Cited by 25 · see citing works
“However, its development as an anti-hyperglycemic medication has been limited due to its poor bioavailability and gastrointestinal side effects [5–7].”
A risk model of gene signatures for predicting platinum response and survival in ovarian cancer
Chen, S.-X., Wu, Y., Wang, S.-M., Wu, J.-C., Wu, X.-H., & Zheng, Z. (2022) · Journal of Ovarian Research · doi:10.1186/s13048-022-00969-3 · Cited by 26 · see citing works
Hwang, J., Lee, S., Huh, W., Han, J.-M., Oh, J., Jang, I., & Yu, K. (2021) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.15348 · Cited by 26 · see citing works
“When SGLT-2 is dysfunctional—as a result of mutations in the SLC5A2 gene—the renal capacity for absorbing glucose decreases to the residual capacity of SGLT-1 (80 g/d).(10)”
BackgroundChan-Zapata, I., Sandoval-Castro, C. A., & Segura-Campos, M. (2020) · Critical reviews in food science and nutrition · doi:10.1080/10408398.2020.1857331 · Cited by 26 · see citing works
“However, some of these inhibitors are in clinical trials, so further studies are necessary before their possible therapeutic application (Rieg and Vallon 2018).”
BackgroundDisruption of energy utilization in diabetic cardiomyopathy; a mini review
Nirengi, S., da Silva, C. P. V., & Stanford, K. I. (2020) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2020.08.015 · Cited by 34 · see citing works
“SGLT2 inhibitors such as empagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) are the newest class of oral hypoglycemic agents approved by the Food and Drug Administration [74] and commercially available for T2D treatment.”
BackgroundInfluentialBridging the gap: glucose transporters, Alzheimer’s, and future therapeutic prospects
Albaik, M., Saleh, D. S., Kauther, D., Mohammed, H., Alfarra, S., Alghamdi, A., Ghaboura, N., & Sindi, I. A. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1344039 · Cited by 29 · see citing works
“SGLT2 inhibitors have demonstrated great success in the treatment of type 2 diabetes mellitus, in addition to having been found to have advantageous effects on the cardiovascular system, kidneys, and Alzheimer ’ s disease (Rieg and Vallon, 2018; Esterline et al., 2020; Nishimura et al., 2022).”
Montalbano, G., Maugeri, A., Guerrera, M. C., Miceli, N., Navarra, M., Barreca, D., Cirmi, S., & Germanà, A. (2021) · Molecules · doi:10.3390/molecules26041119 · Cited by 25 · see citing works
“, dihydrochalcones) can influence carbohydrate uptake [55] or inhibit the enzymes involved in the metabolization of polysaccharides into monomers [56], hence inducing caloric restriction with remarkable anti-obesity effects.”
BackgroundDavid-Silva, A., Esteves, J. V. D. C., Morais, M., Freitas, H. S., Zorn, T. M. T., Corrêa‐Giannella, M. L., & Machado, U. F. (2020) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s242282 · Cited by 35 · see citing works
Ion channels and transporters in diabetic kidney disease
Spires, D. R., Manis, A. D., & Staruschenko, A. (2019) · Current topics in membranes · doi:10.1016/bs.ctm.2019.01.001 · Cited by 30 · see citing works
Aristizábal-Colorado, D., Corredor-Rengifo, D., Sierra-Castillo, S., López-Corredor, C., Trujillo, D. A. V., Weir-Restrepo, D., Izquierdo‐Condoy, J. S., Ortiz‐Prado, E., Rico-Fontalvo, J. E., Gomez‐Mesa, J., et al. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1605746 · Cited by 21 · see citing works
“Its discovery traces back over 150 years to research on glucosuria (22).”
Unveiling the anticancer effects of SGLT-2i: mechanisms and therapeutic potential
Sun, M., Sun, J., Sun, W., Li, X., Wang, Z., Sun, L., & Wang, Y. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1369352 · Cited by 23 · see citing works
“Moreover, their impeccable safety record in humans has prompted investigations into their viability as prospective treatments for various non-metabolic disorders (Rieg and Vallon, 2018).”
BackgroundTubular effects of sodium–glucose cotransporter 2 inhibitors: intended and unintended consequences
Rieg, J. A. D., Xue, J., & Rieg, T. (2020) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000632 · Cited by 30 · see citing works
“The latter are a novel class of antidiabetic drugs [3] that have been approved for the treatment of diabetes mellitus by the US Food and Drug Administration.”
BackgroundSelf-citationMedical and Nonmedical Applications of Synthetic Transmembrane Anion Transporters
Rathnaweera, U. M. C., Chowdhury, S. M., Salam, R., & Busschaert, N. (2025) · Chemical Reviews · doi:10.1021/acs.chemrev.5c00129 · Cited by 36 · see citing works
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“Of note, SGLT2 inhibitors show substantial variance in pharmacological selectivity to SGLT2 over SGLT1 1,11,12 .”
BackgroundMethodGLP-1 Analogs, SGLT-2, and DPP-4 Inhibitors: A Triad of Hope for Alzheimer’s Disease Therapy
Złotek, M., Kurowska, A., Herbet, M., & Piątkowska‐Chmiel, I. (2023) · Biomedicines · doi:10.3390/biomedicines11113035 · Cited by 30 · see citing works
“This group of antidiabetic drugs shows also favorable effects on the cardiovascular system, and it is especially recommended for patients with type 2 diabetes and diagnosed cardiovascular disease [205].”
BackgroundAziri, B., Begić, E., Јаnkovic, S., Mladenović, Z., Stanetić, B., Kovačević-Preradović, T., Iglica, A., & Mujaković, A. (2023) · ESC Heart Failure · doi:10.1002/ehf2.14355 · Cited by 30 · see citing works
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Lee, S., Min, K. W., Lee, B., Jeong, I., Yoo, S.-J., Kwon, H., Choi, Y., & Yoon, K. (2020) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2019.0203 · Cited by 28 · see citing works
“The risk of hypoglycemia is low due to the compensatory role of SGLT1 in the downstream late proximal tubule and counterregulatory mechanisms, including an increase in plasma glucagon levels and hepatic gluconeogenesis [12-14].”
BackgroundMetabolism and disposition of the SGLT2 inhibitor bexagliflozin in rats, monkeys and humans
Zhang, W., Li, X., Ding, H., Lu, Y., Stilwell, G. E., Halvorsen, Y., & Welihinda, A. (2020) · Xenobiotica; the fate of foreign compounds in biological systems · doi:10.1080/00498254.2019.1654634 · Cited by 23 · see citing works
“Affected individuals do not show substantial glucosuria (Rieg & Vallon, 2018).”
BackgroundBurggraaff, L., Oranje, P., Gouka, R., van der Pijl, P. C., Geldof, M., van Vlijmen, H. V., IJzerman, A., & van Westen, G. V. (2019) · Journal of Cheminformatics · doi:10.1186/s13321-019-0337-8 · Cited by 23 · see citing works
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Dasari, D., Goyal, S., Penmetsa, A., Sriram, D., & Dhar, A. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175720 · Cited by 21 · see citing works
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Phloretin alleviates dinitrochlorobenzene-induced dermatitis in BALB/c mice
Wu, C.-S., Lin, S.-C., Li, S.-M., Chiang, Y.-C., Bracci, N. R., Lehman, C., Tang, K.-T., & Lin, C.-C. (2020) · International Journal of Immunopathology and Pharmacology · doi:10.1177/2058738420929442 · Cited by 20 · see citing works
Imai, T., Kato, N., Kanda, N., Hashimoto, H., Yamana, H., & Hatakeyama, S. (2024) · Diabetes Therapy · doi:10.1007/s13300-024-01613-7 · Cited by 19 · see citing works
“Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a relatively new class of oral antihyper-glycemic agents that suppress glucose reuptake in the renal tubular system [1].”
Zhao, Y., Li, M., Wang, Y., Geng, R., Fang, J., Liu, Q., Kang, S., Zeng, W., Huang, K., & Tong, T. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2045895 · Cited by 28 · see citing works
PKCδ-mediated SGLT1 upregulation confers the acquired resistance of NSCLC to EGFR TKIs
Chen, C.-H., Wang, B.-W., Hsiao, Y.-C., Wu, C.-Y., Cheng, F.-J., Hsia, T., Chen, C.-Y. Y., Wang, Y.-H., Zhang, W.-H., Chou, R.-H., et al. (2021) · Oncogene · doi:10.1038/s41388-021-01889-0 · Cited by 19 · see citing works
Shetty, S. S., & KRUMERMAN, A. K. (2022) · Cardiovascular Diabetology · doi:10.1186/s12933-022-01552-2 · Cited by 19 · see citing works
Relevance of solute carrier family 5 transporter defects to inherited and acquired human disease
Cannizzaro, M., Jarošová, J., & Paepe, B. D. (2019) · Journal of Applied Genetics · doi:10.1007/s13353-019-00502-1 · Cited by 18
Sussman, W., Stevenson, M., Mowdawalla, C., Mota, S., Ragolia, L., & Pan, X. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00058.2019 · Cited by 23 · see citing works
“SGLT1 is an essential transporter of both sodium and glucose across the apical membrane of epithelial cells, and its primary function is to regulate glucose uptake by the intestine and kidney (15, 42).”
BackgroundJahangiri, S., Malek, M., Kalra, S., & Khamseh, M. E. (2023) · Diabetes Therapy · doi:10.1007/s13300-023-01481-7 · Cited by 16 · see citing works
“In individuals with diabetes, SGLT2 proteins are paradoxically upregulated, resulting in excessive glucose reabsorption despite high blood glucose levels [33].”
BackgroundPotential Therapeutic Strategies in the Treatment of Metabolic-Associated Fatty Liver Disease
Bołdys, A., Bułdak, Ł., Maligłówka, M., Surma, S., & Okopień, B. (2023) · Medicina · doi:10.3390/medicina59101789 · Cited by 17 · see citing works
“By inducing glucosuria, they subsequently lower serum glucose levels [18].”
BackgroundPharmacogenetics of new classes of antidiabetic drugs
Kadrić, S. I., Ćesić, A. K., & Dujić, T. (2021) · Bosnian Journal of Basic Medical Sciences · doi:10.17305/bjbms.2021.5646 · Cited by 17 · see citing works
“from the renal proximal tubule, leading to glycosuria [13-16].”
BackgroundNew functions and roles of the Na+-H+-exchanger NHE3
Rieg, J. D. D., & Rieg, T. (2024) · Pflügers Archiv: European Journal of Physiology · doi:10.1007/s00424-024-02938-9 · Cited by 16 · see citing works
“Drugs targeting sodium-glucose co-transporters (“gliflozins”) are a new mainstay in the treatment of diabetes mellitus and heart failure [12, 13, 55, 62].”
Self-citation
- Authors
- Rieg, T., & Vallon, V.
- Affiliations
- University of South Florida (US)
- University of California San Diego (US)
- Corresponding author
- Rieg, Timo
- Vallon, Volker
- Venue
- Diabetologia
- Published
- 2018-08-22
- Volume
- 61
- Issue
- 10
- Pages
- 2079-2086
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC6124499
- OpenAlex
- W2883581800
- Cited by
- 377
- References
- 71
- Citations by year
- 2026: 39 · 2025: 53 · 2024: 49 · 2023: 66 · 2022: 58 · 2021: 50 · 2020: 36 · 2019: 24 · 2018: 2
- FWCI
- 4.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK112042)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- SGLT1 inhibitors, SGLT2 inhibitors, sodium-glucose cotransporter, SGLT1, SLC5A2, phloridzin, glucose-galactose malabsorption, glycosuria, type 2 diabetes, heart failure, renal protection, drug discovery, mathematical modeling, genetically engineered mouse models, intestinal glucose absorption, renal glucose reabsorption
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Animals, Blood Glucose, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Disease Models, Animal, Glucose, Humans, Intestinal Mucosa, Kidney, Mutation, Phlorhizin, Drug Design, Diabetic Ketoacidosis, Sodium-Glucose Transporter 1, Sodium-Glucose Transporter 2, Mice
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