Sodium-Glucose Cotransport Inhibition With Dapagliflozin in Type 2 Diabetes
Open accessAbstract
OBJECTIVE: Dapagliflozin, a novel inhibitor of renal sodium-glucose cotransporter 2, allows an insulin-independent approach to improve type 2 diabetes hyperglycemia. In this multiple-dose study we evaluated the safety and efficacy of dapagliflozin in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Type 2 diabetic patients were randomly assigned to one of five dapagliflozin doses, metformin XR, or placebo for 12 weeks. The primary objective was to compare mean change from baseline in A1C. Other objectives included comparison of changes in fasting plasma glucose (FPG), weight, adverse events, and laboratory measurements. RESULTS: After 12 weeks, dapagliflozin induced moderate glucosuria (52–85 g urinary glucose/day) and demonstrated significant glycemic improvements versus placebo (ΔA1C −0.55 to −0.90% and ΔFPG −16 to −31 mg/dl). Weight loss change versus placebo was −1.3 to −2.0 kg. There was no change in renal function. Serum uric acid decreased, serum magnesium increased, serum phosphate increased at higher doses, and dose-related 24-h urine volume and hematocrit increased, all of small magnitude. Treatment-emergent adverse events were similar across all groups. CONCLUSIONS: Dapagliflozin improved hyperglycemia and facilitates weight loss in type 2 diabetic patients by inducing controlled glucosuria with urinary loss of ∼200–300 kcal/day. Dapagliflozin treatment demonstrated no persistent, clinically significant osmolarity, volume, or renal status changes.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Dapagliflozin has demonstrated efficacy, alone or in combination with metformin, in reducing hyperglycemia in patients with type 2 diabetes.
“Dapagliflozin, a highly selective inhibitor of SGLT2, has demonstrated efficacy, alone or in combination with metformin, in reducing hyperglycemia in patients with type 2 diabetes [35,36].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [36]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Levey, A. S., Bosch, J. P., Lewis, J. B., Greene, T., Rogers, N., Roth, D., & for the Modification of Diet in Renal Disease Study Group* (1999) · Annals of Internal Medicine · doi:10.7326/0003-4819-130-6-199903160-00002 · Cited by 15,079 · see citing works
The Metabolic Basis of Inherited Disease.
(1988) · Annals of Internal Medicine · doi:10.7326/0003-4819-108-3-503_7 · Cited by 7,807 · see citing works
10-year follow-up of intensive glucose control in type 2 diabetes
Holman, R. R., Paul, S. K., Bethel, M. A., Matthews, D. R., & Neil, H. A. W. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0806470 · Cited by 7,751 · see citing works
Islet cell failure in type 2 diabetes
Prentki, M. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29103 · Cited by 1,690 · see citing works
Standards of Medical Care in Diabetes—2008
Dora, J. M., Kramer, C. K., & Canani, L. H. S. (2008) · Diabetes Care · doi:10.2337/dc08-0109 · Cited by 1,414 · see citing works
Standards of Medical Care in Diabetes—2008
American Diabetes Association (2008) · Diabetes Care · doi:10.2337/dc08-s012 · Cited by 1,377 · see citing works
The metabolic basis of inherited disease
Goldstein, J. (1995) · Medical Entomology and Zoology · Cited by 1,017 · see citing works
Rossetti, L., Smith, D. J., Shulman, G. I., Papachristou, D. N., & DeFronzo, R. A. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112981 · Cited by 808 · see citing works
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., et al. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm701272q · Cited by 634 · see citing works
Kanai, Y., Lee, W. S., You, G., Brown, D., & Hediger, M. A. (1994) · Journal of Clinical Investigation · doi:10.1172/jci116972 · Cited by 628 · see citing works
Active sugar transport in health and disease
Wright, E. M., Hirayama, B. A., & Loo, D. F. (2007) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2006.01746.x · Cited by 627 · see citing works
Dapagliflozin, a Selective SGLT2 Inhibitor, Improves Glucose Homeostasis in Normal and Diabetic Rats
Han, S., Hagan, D. L., Taylor, J. R., Xin, L., Meng, W., Biller, S. A., Wetterau, J. R., Washburn, W. N., & Whaley, J. M. (2008) · Diabetes · doi:10.2337/db07-1472 · Cited by 422 · see citing works
Molecular physiology of sodium-glucose cotransporters.
Hediger, M. A., & Rhoads, D. B. (1994) · Physiological Reviews · doi:10.1152/physrev.1994.74.4.993 · Cited by 417 · see citing works
Molecular Analysis of the SGLT2 Gene in Patients with Renal Glucosuria
Santer, R., Kinner, M., Lassen, C. L., Schneppenheim, R., Eggert, P., Bald, M., Brodehl, J., Daschner, M., Ehrich, J. H. H., Kemper, M., et al. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000092790.89332.d2 · Cited by 304 · see citing works
Executive Summary: Standards of Medical Care in Diabetes—2014
(2013) · Diabetes Care · doi:10.2337/dc14-s005 · Cited by 293 · see citing works
Diabetes‐associated macrovasculopathy: pathophysiology and pathogenesis
Rahman, S., Rahman, T., Ismail, A. A.-S., & Rashid, A. R. A. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2006.00655.x · Cited by 247 · see citing works
van den Heuvel, L. P., Assink, K., Willemsen, M. A. A. P., & Monnens, L. A. H. (2002) · Human Genetics · doi:10.1007/s00439-002-0820-5 · Cited by 220 · see citing works
Andrews, W. J., Vasquez, B., NAGULESPARAN, M., Klimeś, I., Foley, J. E., Unger, R. H., & Reaven, G. M. (1984) · Diabetes · doi:10.2337/diab.33.7.634 · Cited by 194 · see citing works
EFFECT OF DIABETES AND INSULIN ON THE MAXIMUM CAPACITY OF THE RENAL TUBULES TO REABSORB GLUCOSE 1
Färber, S. J., Berger, E. Y., & Earle, D. P. (1951) · Journal of Clinical Investigation · doi:10.1172/jci102424 · Cited by 186 · see citing works
Kahn, B. B., Shulman, G. I., DeFronzo, R. A., Cushman, S. W., & Rossetti, L. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115031 · Cited by 171 · see citing works
Risk of macrovascular and microvascular complications in Type 2 diabetes
Nazimek-Siewniak, B., Moczulski, D. K., & Grzeszczak, W. (2002) · Journal of Diabetes and its Complications · doi:10.1016/s1056-8727(01)00184-2 · Cited by 88 · see citing works
Ribera, M. C., Pascual, R., Orozco‐Beltrán, D., et al. (2006) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-006-0148-5 · Cited by 88 · see citing works
Kles, K. A., & Vinik, A. I. (2006) · Current Diabetes Reviews · doi:10.2174/157339906776818569 · Cited by 62 · see citing works
State of diabetes care in the United States.
Blonde, L. (2007) · PubMed · Cited by 44 · see citing works
Phlorizin Induces Lipolysis and Alters Meal Patterns in Both Early-and Late-Lactation Dairy Cows
Bradford, B. J., & Allen, M. S. (2007) · Journal of Dairy Science · doi:10.3168/jds.2006-631 · Cited by 16 · see citing works
Efficacy and Safety of Incretin Therapy in Type 2 Diabetes: Systematic Review and Meta-analysis
Amori, R. E., Lau, J., & Pittas, A. G. (2007) · JAMA · doi:10.1001/jama.298.2.194 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Biology of Human Sodium Glucose Transporters
Wright, E. M., Loo, D. D. F., & Hirayama, B. A. (2011) · Physiological Reviews · doi:10.1152/physrev.00055.2009 · Cited by 1,430 · see citing works
Cherney, D. Z. I., Perkins, B. A., Soleymanlou, N., Maione, M., Lai, V., Lee, A., Fagan, N. M., Woerle, H. J., Johansen, O. E., Broedl, U. C., et al. (2014) · Circulation · doi:10.1161/circulationaha.113.005081 · Cited by 1,329 · see citing works
Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes
Lambers Heerspink, H. J., de Zeeuw, D., Wie, L., Leslie, B., & List, J. (2013) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12127 · Cited by 837 · see citing works
Self-citationUpdate on the treatment of type 2 diabetes mellitus
Marín-Peñalver, J. J., Martín-Timón, I., Sevillano-Collantes, C., & Cañizo-Gómez, F. J. D. (2016) · World Journal of Diabetes · doi:10.4239/wjd.v7.i17.354 · Cited by 647 · see citing works
Kohan, D. E., Fioretto, P., Tang, W., & List, J. F. (2014) · Kidney International · doi:10.1038/ki.2013.356 · Cited by 652 · see citing works
Self-citationMetformin: An Old But Still the Best Treatment for Type 2 Diabetes
Rojas, L. B. A., & Gomes, M. B. (2013) · Diabetology & Metabolic Syndrome · doi:10.1186/1758-5996-5-6 · Cited by 567 · see citing works
Cherney, D. Z., Perkins, B. A., Soleymanlou, N., Har, R., Fagan, N., Johansen, O., Woerle, H.-J., von Eynatten, M., & Broedl, U. C. (2014) · Cardiovascular Diabetology · doi:10.1186/1475-2840-13-28 · Cited by 470 · see citing works
Baker, W. L., Smyth, L. R., Riche, D. M., Bourret, E. M., Chamberlin, K. W., & White, W. B. (2014) · Journal of the American Society of Hypertension · doi:10.1016/j.jash.2014.01.007 · Cited by 452 · see citing works
Heerspink, H. J. L., Perco, P., Mulder, S., Leierer, J., Hansen, M. K., Heinzel, A., & Mayer, G. (2019) · Diabetologia · doi:10.1007/s00125-019-4859-4 · Cited by 457 · see citing works
Mazidi, M., Rezaie, P., Gao, H., & Kengne, A. P. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.116.004007 · Cited by 347 · see citing works
Update on developments with SGLT2 inhibitors in the management of type 2 diabetes
Nauck, M. (2014) · Drug Design, Development and Therapy · doi:10.2147/dddt.s50773 · Cited by 343 · see citing works
Toyama, T., Neuen, B. L., Jun, M., Ohkuma, T., Neal, B., Jardine, M. J., Heerspink, H. L., Wong, M. G., Ninomiya, T., Wada, T., et al. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13648 · Cited by 330 · see citing works
DeFronzo, R. A., Hompesch, M., Kasichayanula, S., Liu, X., Hong, Y., Pfister, M., Morrow, L. A., Leslie, B. R., Boulton, D. W., Ching, A., et al. (2013) · Diabetes Care · doi:10.2337/dc13-0387 · Cited by 293 · see citing works
Han, J. H., Oh, T. J., Lee, G., Maeng, H. J., Lee, D. H., Kim, K. M., Choi, S. H., Jang, H. C., Lee, H. S., Park, K. S., et al. (2017) · Diabetologia · doi:10.1007/s00125-016-4158-2 · Cited by 281 · see citing works
Kasichayanula, S., Liu, X., LaCreta, F., Griffen, S. C., & Boulton, D. W. (2014) · Clinical Pharmacokinetics · doi:10.1007/s40262-013-0104-3 · Cited by 276 · see citing works
Model-Based Drug Development: A Rational Approach to Efficiently Accelerate Drug Development
Milligan, P. A., Brown, M. J., Marchant, B., Martin, S. W., van der Graaf, P. H., Benson, N., Nucci, G., Nichols, D. J., Boyd, R. A., Mandema, J. W., et al. (2013) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2013.54 · Cited by 238 · see citing works
Donnan, J. R., Grandy, C. A., Chibrikov, E., Marra, C. A., Aubrey-Bassler, K., Johnston, K., Swab, M., Hache, J., Curnew, D., Nguyen, H., et al. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-022577 · Cited by 222 · see citing works
Drug therapy in obesity: a review of current and emerging treatments
Williams, D. M., Nawaz, A., & Evans, M. (2020) · Diabetes Therapy · doi:10.1007/s13300-020-00816-y · Cited by 195 · see citing works
Fioretto, P., Del Prato, S., Buse, J. B., Goldenberg, R., Giorgino, F., Reyner, D., Langkilde, A. M., Sjöström, C. D., Sartipy, P., & On Behalf of the DERIVE Study Investigators (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13413 · Cited by 195 · see citing works
Lee, P. C., Ganguly, S., & Goh, S. ‐. (2018) · Obesity Reviews · doi:10.1111/obr.12755 · Cited by 189 · see citing works
Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans
List, J. F., & Whaley, J. M. (2011) · Kidney International · doi:10.1038/ki.2010.512 · Cited by 184 · see citing works
Self-citationCai, X., Yang, W., Gao, X., Chen, Y., Zhou, L., Zhang, S., Han, X., & Ji, L. (2018) · Obesity · doi:10.1002/oby.22066 · Cited by 181 · see citing works
Cefalu, W. T., Leiter, L. A., de Bruin, T. W. A., Gause-Nilsson, I., Sugg, J., & Parikh, S. J. (2015) · Diabetes Care · doi:10.2337/dc14-0315 · Cited by 182 · see citing works
Jackson, A. M., Dewan, P., Anand, I. S., Bělohlávek, J., Bengtsson, O., de Boer, R. A., Böhm, M., Boulton, D. W., Chopra, V. K., DeMets, D. L., et al. (2020) · Circulation · doi:10.1161/circulationaha.120.047077 · Cited by 175 · see citing works
Wilcox, C. S., Shen, W., Boulton, D. W., Leslie, B. R., & Griffen, S. C. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.117.007046 · Cited by 139 · see citing works
Woods, T. C., Satou, R., Miyata, K., Katsurada, A., Dugas, C. M., Klingenberg, N. C., Fonseca, V. A., & Navar, L. G. (2019) · American Journal of Nephrology · doi:10.1159/000499597 · Cited by 124 · see citing works
The Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Sympathetic Nervous Activity
Wan, N., Rahman, A., Hitomi, H., & Nishiyama, A. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00421 · Cited by 115 · see citing works
Dekkers, C. C. J., Sjöström, C. D., Greasley, P. J., Cain, V., Boulton, D. W., & Heerspink, H. J. L. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13855 · Cited by 106 · see citing works
Sjöström, C. D., Johansson, P., Ptaszynska, A., List, J., & Johnsson, E. (2015) · Diabetes and Vascular Disease Research · doi:10.1177/1479164115585298 · Cited by 97 · see citing works
Self-citationIrace, C., Casciaro, F., Scavelli, F. B., Oliverio, R., Cutruzzolà, A., Cortese, C., & Gnasso, A. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0695-y · Cited by 74 · see citing works
Chiba, Y., Yamada, T., Tsukita, S., Takahashi, K., Munakata, Y., Shirai, Y., Kodama, S., Asai, Y., Sugisawa, T., Uno, K., et al. (2016) · PLOS ONE · doi:10.1371/journal.pone.0150756 · Cited by 71 · see citing works
Shaikh, S., Rizvi, S. M. D., Shakil, S., Riyaz, S., Biswas, D., & Jahan, R. (2016) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.1319 · Cited by 70 · see citing works
Imprialos, K. P., Sarafidis, P. A., & Karagiannis, A. I. (2015) · Journal of Hypertension · doi:10.1097/hjh.0000000000000719 · Cited by 71 · see citing works
Scheen, A. J. (2016) · Diabetes & Metabolism · doi:10.1016/j.diabet.2016.05.006 · Cited by 64 · see citing works
Cai, X., Gao, X., Yang, W., Chen, Y., Zhang, S., Zhou, L., Han, X., & Ji, L. (2018) · Journal of Diabetes Investigation · doi:10.1111/jdi.12760 · Cited by 64 · see citing works
Trujillo, J. M., & Nuffer, W. A. (2017) · Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.1903 · Cited by 42 · see citing works
Dorsey-Treviño, E. G., González-González, J. G., Alvarez-Villalobos, N., González-Nava, V., Contreras-Garza, B. M., Díaz González-Colmenero, A., Rodríguez-Tamez, G., Barrera-Flores, F. J., Farrell, A. M., Montori, V. M., et al. (2020) · Journal of Endocrinological Investigation · doi:10.1007/s40618-019-01103-9 · Cited by 39 · see citing works
Wang, C., Zhou, Y., Kong, Z., Wang, X., Lv, W., Geng, Z., & Wang, Y. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13620 · Cited by 39 · see citing works
Sotagliflozin as a potential treatment for type 2 diabetes mellitus
Cariou, B., & Charbonnel, B. (2015) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2015.1100361 · Cited by 37 · see citing works
The kidney as a new target for antidiabetic drugs: SGLT2 inhibitors
Cangoz, S., Chang, Y.-Y., Chempakaseril, S. J., Guduru, R. C., Huynh, L. M., John, J. S., John, S. T., Joseph, M. E., Judge, R., Kimmey, R., et al. (2013) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.12077 · Cited by 35 · see citing works
Sawada, Y., Izumida, Y., Takeuchi, Y., Aita, Y., Wada, N., Li, E., Murayama, Y., Piao, X., Shikama, A., Masuda, Y., et al. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.09.081 · Cited by 31 · see citing works
Sodium glucose co-transporter inhibitors—A new class of old drugs
Malhotra, P., Malhotra, A., Kudyar, S., Gupta, A., & Kudyar, R. (2015) · International Journal of Applied and Basic Medical Research · doi:10.4103/2229-516x.165363 · Cited by 21 · see citing works
Recent progress in the pharmacotherapy for obesity
Lu, J., Liu, P., Cai, M., Lv, T., Zhang, M., Yin, K., Cheng, J., & Zhang, G. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177850 · Cited by 17 · see citing works
- Authors
- List, J. F., Woo, V., Morales, E., Tang, W., & Fiedorek, F. T.
- Affiliations
- Bristol-Myers Squibb (United States) (US)
- University of Manitoba (CA)
- Centro de Investigación Cardiometabólica, Aguascalientes, Mexico;
- Corresponding author
- List, James F.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2008-12-29
- Volume
- 32
- Issue
- 4
- Pages
- 650-657
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC2660449
- OpenAlex
- W2150855258
- Cited by
- 698
- References
- 26
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 25 · 2023: 34 · 2022: 34 · 2021: 33 · 2020: 33 · 2019: 42 · 2018: 41 · 2017: 52 · 2016: 46 · 2015: 56 · 2014: 64 · 2013: 67 · 2012: 45
- FWCI
- 23.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- Bristol-Myers Squibb
- European Foundation for the Study of Diabetes
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- dapagliflozin, SGLT2 inhibitors, type 2 diabetes, glycemic control, HbA1c, fasting blood glucose, glycosuria, weight loss, metformin, adverse events, serum uric acid, renal function
- MeSH terms
- Adolescent, Adult, Aged, Benzhydryl Compounds, Blood Glucose, Diabetes Mellitus, Type 2, Diuretics, Dose-Response Relationship, Drug, Female, Glucosides, Glycosuria, Glycated Hemoglobin, Humans, Hyperglycemia, Hypoglycemic Agents, Male, Metformin, Middle Aged, Placebos, Weight Loss, Sodium-Glucose Transport Proteins, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
