Cited by 1,134Diabetes Treatment and ManagementDiabetes Management and ResearchMetabolism, Diabetes, and Cancer

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Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients

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Ferrannini, Ele, Muscelli, Elza, Frascerra, Silvia, Baldi, Simona, Mari, Andrea, Heise, Tim, Broedl, Uli C., Woerle, Hans-Juergen·2014·Journal of Clinical Investigation

DOI 10.1172/jci72227PMC PMC3904627

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Abstract

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower glycemia by enhancing urinary glucose excretion. The physiologic response to pharmacologically induced acute or chronic glycosuria has not been investigated in human diabetes. METHODS: We evaluated 66 patients with type 2 diabetes (62 ± 7 years, BMI = 31.6 ± 4.6 kg/m(2), HbA1c = 55 ± 8 mmol/mol, mean ± SD) at baseline, after a single dose, and following 4-week treatment with empagliflozin (25 mg). At each time point, patients received a mixed meal coupled with dual-tracer glucose administration and indirect calorimetry. RESULTS: Both single-dose and chronic empagliflozin treatment caused glycosuria during fasting (median, 7.8 [interquartile range {IQR}, 4.4] g/3 hours and 9.2 [IQR, 5.2] g/3 hours) and after meal ingestion (median, 29.0 [IQR, 12.5] g/5 hours and 28.2 [IQR, 15.4] g/5 hours). After 3 hours of fasting, endogenous glucose production (EGP) was increased 25%, while glycemia was 0.9 ± 0.7 mmol/l lower (P < 0.0001 vs. baseline). After meal ingestion, glucose and insulin AUC decreased, whereas the glucagon response increased (all P < 0.001). While oral glucose appearance was unchanged, EGP was increased (median, 40 [IQR, 14] g and 37 [IQR, 11] g vs. 34 [IQR, 11] g, both P < 0.01). Tissue glucose disposal was reduced (median, 75 [IQR, 16] g and 70 [IQR, 21] g vs. 93 [IQR, 18] g, P < 0.0001), due to a decrease in both glucose oxidation and nonoxidative glucose disposal, with a concomitant rise in lipid oxidation after chronic administration (all P < 0.01). β Cell glucose sensitivity increased (median, 55 [IQR, 35] pmol • min(-1) • m(-2) • mM(-1) and 55 [IQR, 39] pmol • min(-1) • m(-2) • mM(-1) vs. 44 [IQR, 32] pmol • min(-1) • m(-2) • mM(-1), P < 0.0001), and insulin sensitivity was improved. Resting energy expenditure rates and those after meal ingestion were unchanged. CONCLUSIONS: In patients with type 2 diabetes, empagliflozin-induced glycosuria improved β cell function and insulin sensitivity, despite the fall in insulin secretion and tissue glucose disposal and the rise in EGP after one dose, thereby lowering fasting and postprandial glycemia. Chronic dosing shifted substrate utilization from carbohydrate to lipid. Trial registration. ClinicalTrials.Gov NCT01248364 (EudraCT no. 2010-018708-99). Funding. This study was funded by Boehringer Ingelheim.

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(‐)‐Epicatechin and the Colonic 2,3‐Dihydroxybenzoic Acid Metabolite Regulate Glucose Uptake, Glucose Production, and Improve Insulin Signaling in Renal NRK‐52E Cells
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“glucagon levels [23, 24], which may increase magnesium reabsorption in the distal convo-”
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Background
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“Consistent with previous studies (3 – 6), inhibition of renal SGLT2 transport with dapagli ﬂ ozin was associated with a signi ﬁ cant decrease in the plasma glucose concentration ( 2 12 mg/dL) and a “ paradoxical ” increase in EGP with a concomitant increase in the plasma glucagon concentration and…”
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Background
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Background
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“The expected weight loss based on these urinary glucose losses over 6–12 months is about 7–8 kg, but in clinical trials in people with diabetes, it is usually only about 2–3 kg with such agents, suggesting compensatory hyperphagia, which is supported by data from preclinical and clinical studies (Devenny et al., 2012;…”
Background
Empagliflozin decreases remnant‐like particle cholesterol in type 2 diabetes patients with insulin resistance
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Increase in endogenous glucose production with SGLT2 inhibition is attenuated in individuals who underwent kidney transplantation and bilateral native nephrectomy
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Self-citation
Effects of sodium‐glucose cotransporter type 2 inhibitors on cardiovascular, renal, and safety outcomes in patients with cardiovascular disease: a meta‐analysis of randomized controlled trials
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“For example, these compounds have been reported to lower blood pressure [30], blood lipid levels [31, 32], and body weight [32, 33]; however, the exact mechanisms through which such drugs improve cardiovascular outcomes remain unclear.”
Background
A Role for SGLT-2 Inhibitors in Treating Non-diabetic Chronic Kidney Disease
Vecchio, L. D., Beretta, A., Jovane, C., Peiti, S., & Genovesi, S. (2021) · Drugs · doi:10.1007/s40265-021-01573-3 · Cited by 37
“The improvement of arrhythmia and myocardial function related to higher levels of glucagon may contribute to a decrease in heart failure and cardiovascular mortality risk [136, 137].”
Background
Sodium-glucose cotransport inhibitors: mechanisms, metabolic effects and implications for the treatment of diabetic patients with chronic kidney disease: FIGURE 1:
Vlotides, G., & Mertens, P. R. (2014) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfu299 · Cited by 36
Response to Comment on Rubino et al. Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations. Diabetes Care 2016;39:861–877
Cummings, D. E., & Rubino, F. (2016) · Diabetes Care · doi:10.2337/dci16-0031 · Cited by 41
Involvement of steatosis-induced glucagon resistance in hyperglucagonaemia
Suppli, M. P., Lund, A., Bagger, J. I., Vilsbøll, T., & Knop, F. K. (2016) · Medical Hypotheses · doi:10.1016/j.mehy.2015.10.029 · Cited by 35
“Pharmaceuticals of interest are, among others, metformin, shown to suppress hepatic glucagon signalling [27], glucagon-like peptide-1 receptor agonists, which result in weight loss and reduced glucagon secretion [28], dipeptidyl peptidase 4 inhibitors, which reduce glucagon levels [29] and sodium-glucose co-transporte…”
Background
How can inhibition of glucose and sodium transport in the early proximal tubule protect the cardiorenal system?
Vallon, V. (2024) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfae060 · Cited by 37
The potential anti-arrhythmic effect of SGLT2 inhibitors
Duan, H.-Y., Barajas-Martínez, H., Antzelevitch, C. N., & Hu, D. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02312-0 · Cited by 35
“Body and fat mass loss can ascribe to SGLT2i leading to a fuel utilization shift from carbohydrate to fat substrates, that has been investigated in human and animal studies [91, 92].”
Background
Exploring the Role of SGLT2 Inhibitors in Cancer: Mechanisms of Action and Therapeutic Opportunities
Pandey, A., Alcaraz, M., Saggese, P., Soto, A., Gomez, E., Jaldu, S., Yanagawa, J., & Scafoglio, C. (2025) · Cancers · doi:10.3390/cancers17030466 · Cited by 35
“One of the main effects of SGLT2is is the reduction in circulating insulin [30] (Figure 3).”
EMPA-REG and Other Cardiovascular Outcome Trials of Glucose-lowering Agents: Implications for Future Treatment Strategies in Type 2 Diabetes Mellitus
Schernthaner, G., Schernthaner-Reiter, M. H., & Schernthaner, G.-H. (2016) · Clinical Therapeutics · doi:10.1016/j.clinthera.2016.04.037 · Cited by 38
Place of sodium-glucose cotransporter-2 inhibitors in East Asian subjects with type 2 diabetes mellitus: Insights into the management of Asian phenotype
Lim, L., Tan, A. T. B., Moses, K., Rajadhyaksha, V., & Chan, S. P. (2016) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2016.10.008 · Cited by 34
Dual SGLT1/SGLT2 Inhibitor Phlorizin Ameliorates Non-Alcoholic Fatty Liver Disease and Hepatic Glucose Production in Type 2 Diabetic Mice
David-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 37
Dapagliflozin exerts positive effects on beta cells, decreases glucagon and does not alter beta- to alpha-cell transdifferentiation in mouse models of diabetes and insulin resistance
Tanday, N., Irwin, N., Flatt, P. R., & Moffett, R. C. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114009 · Cited by 36
Changes in plasma and urine metabolites associated with empagliflozin in patients with type 1 diabetes
Liu, H., Sridhar, V. S., Montemayor, D., Lovblom, L. E., Lytvyn, Y., Ye, H., Kim, J., Ali, M. T., Scarr, D., Lawler, P. R., et al. (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14489 · Cited by 36
“Accordingly, SGLT2 inhibitors may have attenuated effects on insulin-dependent physiological processes in individuals with T1D, although effects could still be present because of other intact endogenous factors, including glucagon.(15) In this post hoc analysis, despite complete insulin replacement in the setting of T…”
Background
Dapagliflozin improves insulin resistance and glucose intolerance in a novel transgenic rat model of chronic glucose overproduction and glucose toxicity
Joannides, C. N., Mangiafico, S. P., Waters, M. F., Lamont, B. J., & Andrikopoulos, S. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12923 · Cited by 35
“Studies in humans have shown that SGLT2 inhibitor treatment of patients with type 2 diabetes improved both insulin resistance(14,16) and insulin secretion, as assessed by a meal tolerance test.(14) This is despite increases in plasma glucagon and endogenous glucose production.”
BackgroundResultInfluential
The effects of SGLT2i on cardiac metabolism in patients with HFpEF: Fact or fiction?
Cinti, F., Laborante, R., Cappannoli, L., Morciano, C., Gugliandolo, S., Pontecorvi, A., Burzotta, F., Donniacuo, M., Cappetta, D., Patti, G., et al. (2025) · Cardiovascular Diabetology · doi:10.1186/s12933-025-02767-9 · Cited by 38
“[39, 40] Furthermore, the excretion of glucose through urine leads to caloric loss, contributing to weight reduction, a particularly beneficial outcome in individuals with T2D.”
The potential role of sodium glucose co-transporter 2 inhibitors in combination therapy for type 2 diabetes mellitus
Lajara, R. (2014) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2014.968551 · Cited by 34
Does dapagliflozin regress left ventricular hypertrophy in patients with type 2 diabetes? A prospective, double-blind, randomised, placebo-controlled study
Brown, A., Lang, C. C., McCrimmon, R. J., & Struthers, A. D. (2017) · BMC Cardiovascular Disorders · doi:10.1186/s12872-017-0663-6 · Cited by 33
“[45] Studies have also shown that treatment with SGLT2 inhibitors improves insulin sensitivity as measured by peripheral glucose uptake [46, 47].”
Background
Major adverse cardiovascular event reduction with GLP-1 and SGLT2 agents: evidence and clinical potential
Røder, M. E. (2017) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622317735283 · Cited by 34
Effects of the sodium‐glucose cotransporter 2 ( SGLT 2) inhibitor velagliflozin, a new drug with therapeutic potential to treat diabetes in cats
Hoenig, M. E., Clark, M., Schaeffer, D. J., & Reiche, D. (2017) · Journal of Veterinary Pharmacology and Therapeutics · doi:10.1111/jvp.12467 · Cited by 34
“The change in insulin sensitivity is in part related to the degree of weight loss and loss of fat mass, which is seen in type 2 diabetic people treated with SGLT2 inhibitors (Ferrannini et al., 2014; Fujita & Inagaki, 2014).”
Background
Possibility of pharmacokinetic drug interaction between a DPP-4 inhibitor and a SGLT2 inhibitor
Gu, N., Park, S., Chung, H., Jin, X., Lee, S., & Kim, T. (2020) · Translational and Clinical Pharmacology · doi:10.12793/tcp.2020.28.e4 · Cited by 35
Disruption 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 35
“Furthermore, SGLT2 inhibitors increase blood ketone body concentration levels in patients with DCM [88,90], likely due to an increase in α-cell induced glucagon or lipolysis [90,91] which can stimulate ketone body production [92,93].”
Background
Sodium-glucose cotransporter 2 inhibitors and mitochondrial functions: state of the art
Yaribeygi, H., Maleki, M., Butler, A. E., Jamialahmadi, T., & Sahebkar, A. (2022) · EXCLI journal · doi:10.17179/excli2022-5482 · Cited by 34
Influence of Familial Renal Glycosuria Due to Mutations in the SLC5A2 Gene on Changes in Glucose Tolerance over Time
Ottosson-Laakso, E., Tuomilehto, J., Forsén, B., Gullström, M., Groop, P., Groop, L., & Vikman, P. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0146114 · Cited by 34
“Furthermore, it has been shown that inhibition of glucose reabsorption by SGLT2 inhibitors increases endogenous glucose production and plasma glucagon concentrations in diabetic subjects [11,12], and nondiabetic mice [13].”
Background
Update review of the safety of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with type 2 diabetes mellitus
Carlson, C. J., & Santamarina, M. L. (2016) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2016.1216100 · Cited by 33
“[72], reduced vascular inflammation [73], and potential positive cardiac effects of increased glucagon levels [68,74,75].”
Background
Impact of the 8-week Administration of Tofogliflozin for Glycemic Control and Body Composition in Japanese Patients with Type 2 Diabetes Mellitus
Hirose, S., Nakajima, S., Iwahashi, Y., Seo, A., Takahashi, T., & Tamori, Y. (2016) · Internal Medicine · doi:10.2169/internalmedicine.55.6367 · Cited by 33
“In fact, several reports have shown that SGLT2 inhibitors stimulate the energy intake to compensate for the caloric loss due to glycosuria, which may be sufficient to offset the weight loss induced by calorie loss to urine (24-26).”
BackgroundInfluential
The effect of acute dual SGLT1/SGLT2 inhibition on incretin release and glucose metabolism after gastric bypass surgery
Martinussen, C., Veedfald, S., Dirksen, C., Bojsen-Møller, K. N., Svane, M. S., Albrechtsen, N. J. W., van Hall, G., Kristiansen, V. B., Fenger, M., Holst, J. J., et al. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00023.2020 · Cited by 33
Cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors in diabetic and nondiabetic patients
Xiang, B., Zhao, X.-Y., & Zhou, X. (2021) · Cardiovascular Diabetology · doi:10.1186/s12933-021-01266-x · Cited by 35
“SGLT2i-induced glycosuria reduces blood glucose and consequently contributes to many metabolic adaptations similar to those in the fasting state, including decreased glucose oxidation, acceleration of lipolysis, augmentation of fat oxidation, and increased plasma concentrations of ketone bodies [88, 98].”
Background
Differential effect of canagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, on slow and fast skeletal muscles from nondiabetic mice
Otsuka, H., Yokomizo, H., Nakamura, S., Izumi, Y., Takahashi, M., Obara, S., Nakao, M., Ikeda, Y., Sato, N., Sakamoto, R., et al. (2022) · Biochemical Journal · doi:10.1042/bcj20210700 · Cited by 35
“Evidence suggested that SGLT2 inhibitors improve the skeletal muscle insulin sensitivity [56,57].”
Dapagliflozin suppresses glucagon signaling in rodent models of diabetes
Wang, M.-Y., Yu, X., Lee, Y., McCorkle, S. K., Chen, S., Li, J., Wang, Z. V., Davidson, J. A., Scherer, P. E., Holland, W. L., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705845114 · Cited by 34
“Recently, two studies of human patients with type 2 diabetes treated with two different SGLT2 inhibitors reported an elevation of endogenous glucose production, as well as increased plasma glucagon levels (4, 5), although the rises in glucagon with acute treatment were quite small, and in one case (4), chronic treatme…”
Background
Effects of Tirzepatide vs Semaglutide on β-Cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test
Mather, K. J., Mari, A., Heise, T., DeVries, J. H., Hua, M., Urva, S., Coskun, T., Haupt, A., Heine, R. J., Pratt, E., et al. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae319 · Cited by 35
Self-citation
SGLT2 inhibitors across various patient populations in the era of precision medicine: the multidisciplinary team approach
McLean, P., Bennett, J., Woods, E. A., Chandrasekhar, S. A., Newman, N. A., Mohammad, Y., Khawaja, M., Rizwan, A. M., Siddiqui, R., Birnbaum, Y., et al. (2025) · npj Metabolic Health and Disease · doi:10.1038/s44324-025-00068-z · Cited by 36
“The primary mechanism by which SGLT2i lower hemoglobin A1c is through glucosuria, which effectively decreases both fasting and postprandial blood glucose levels 16,19,20 .”
Rationale and design of a multicenter placebo-controlled double-blind randomized trial to evaluate the effect of empagliflozin on endothelial function: the EMBLEM trial
Tanaka, A., Shimabukuro, M., Okada, Y., Taguchi, I., Yamaoka‐Tojo, M., Tomiyama, H., Teragawa, H., Sugiyama, S., Yoshida, H., Sato, Y., et al. (2017) · Cardiovascular Diabetology · doi:10.1186/s12933-017-0532-8 · Cited by 32
Increase in Endogenous Glucose Production With SGLT2 Inhibition Is Unchanged by Renal Denervation and Correlates Strongly With the Increase in Urinary Glucose Excretion
Solis-Herrera, C., Daniele, G., Alatrach, M., Agyin, C., Triplitt, C., Adams, J. M., Patel, R., Gastaldelli, A., Honka, H., Chen, X., et al. (2020) · Diabetes Care · doi:10.2337/dc19-2177 · Cited by 19
“We (10,12) and others (13) have demonstrated that the glucosuria produced by SGLT2i stimulates EGP and that the increase in EGP offsets by;50% the amount of glucose lost in the urine.”
Background
Sodium–glucose cotransporter 2 inhibitors represent a paradigm shift in the prevention of heart failure in type 2 diabetes patients
Kashiwagi, A., Araki, S., & Maegawa, H. (2020) · Journal of Diabetes Investigation · doi:10.1111/jdi.13329 · Cited by 32
Metabolic and cardiovascular benefits with combination therapy of SGLT-2 inhibitors and GLP-1 receptor agonists in type 2 diabetes
Singh, A. K., & Singh, R. (2022) · World Journal of Cardiology · doi:10.4330/wjc.v14.i6.329 · Cited by 32
Neutral effect of SGLT2 inhibitors on lipoprotein metabolism: From clinical evidence to molecular mechanisms
Osto, E., Bonacina, F., Pirillo, A., & Norata, G. D. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106667 · Cited by 35
Acquired Disorders of Hypomagnesemia
Rosner, M. H., Ha, N., Palmer, B. F., & Perazella, M. A. (2023) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2022.12.002 · Cited by 37
Comparison of SGLT2 inhibitors with DPP-4 inhibitors combined with metformin in patients with acute myocardial infarction and diabetes mellitus
Lyu, Y. S., Oh, S. K., Kim, J. H., Kim, S. Y., & Jeong, M. H. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01914-4 · Cited by 32
“SGLT2i have been found to modulate cardiac metabolism by increasing reliance on fatty acids as an energy source and promoting ketone body utilization [54, 55].”
Background
Rationale, Design, and Baseline Characteristics of the Utopia Trial for Preventing Diabetic Atherosclerosis Using an SGLT2 Inhibitor: A Prospective, Randomized, Open-Label, Parallel-Group Comparative Study
On behalf of the UTOPIA study investigators, Katakami, N., Mita, T., Yoshii, H., Shiraiwa, T., Yasuda, T., Okada, Y., Umayahara, Y., Kaneto, H., Osonoi, T., et al. (2017) · Diabetes Therapy · doi:10.1007/s13300-017-0292-1 · Cited by 31
Glucagon Levels During Short-Term SGLT2 Inhibition Are Largely Regulated by Glucose Changes in Patients With Type 2 Diabetes
Lundkvist, P., Pereira, M. J., Kamble, P. G., Katsogiannos, P., Langkilde, A. M., ESTERLINE, R. L., JOHNSSON, E. K., & Eriksson, J. W. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00969 · Cited by 31
Molecular signaling mechanisms of renal gluconeogenesis in nondiabetic and diabetic conditions
Swe, M. T., Pongchaidecha, A., Chatsudthipong, V., Chattipakorn, N., & Lungkaphin, A. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27598 · Cited by 31
“Of note, inhibition of SGLT was also followed by a compensatory increase in whole‐body EGP in T2D patients (Ferrannini et al., 2014; Merovci et al., 2014) and enhanced renal gluconeogenic genes expression in STZ‐induced T1D mice and Akita mice (Sasaki et al.”
Background
Effects of novel antidiabetes agents on apoptotic processes in diabetes and malignancy: Implications for lowering tissue damage
Yaribeygi, H., Lhaf, F., Sathyapalan, T., & Sahebkar, A. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.06.013 · Cited by 34
A Review on the Effects of New Anti-Diabetic Drugs on Platelet Function
Yaribeygi, H., Atkin, S. L., Jamialahmadi, T., & Sahebkar, A. (2019) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530319666191014110414 · Cited by 31
Gluconeogenesis, But Not Glycogenolysis, Contributes to the Increase in Endogenous Glucose Production by SGLT-2 Inhibition
Wolf, P. S., Fellinger, P., Pfleger, L., Beiglböck, H., Krumpolec, P., Barbieri, C., Gastaldelli, A., Harreiter, J., Metz, M., Scherer, T., et al. (2020) · Diabetes Care · doi:10.2337/dc20-1983 · Cited by 31
Clinical and biochemical characteristics and analysis of risk factors for euglycaemic diabetic ketoacidosis in type 2 diabetic individuals treated with SGLT2 inhibitors: A review of 72 cases over a 4.5-year period
Menghoum, N., Oriot, P., & Hermans, M. P. (2021) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2021.102275 · Cited by 33
Characteristics and molecular mechanisms through which SGLT2 inhibitors improve metabolic diseases: A mechanism review
Xie, L., & Wenfang, X. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120543 · Cited by 35
Understanding EMPA-REG OUTCOME
Ceriello, A., Genovese, S., Mannucci, E., & Gronda, E. (2015) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(15)00426-x · Cited by 31

Authors: Ferrannini, E., Muscelli, E., Frascerra, S., Baldi, S., Mari, A., Heise, T., Broedl, U. C., & Woerle, H.-J.
Affiliations: University of Pisa (IT)
National Research Council (IT)
Profil Institute for Metabolic Research (DE)
Boehringer Ingelheim (Germany) (DE)
Corresponding author: Ferrannini, Ele
ORCID: Ferrannini, Ele
Muscelli, Elza
Baldi, Simona
Mari, Andrea
Heise, Tim
Broedl, Uli C.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2014-01-27
Volume: 124
Issue: 2
Pages: 499-508
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci72227
PMC: PMC3904627
OpenAlex: W2157405334
Cited by: 1,134
References: 45
Citations by year: 2026: 55 · 2025: 68 · 2024: 80 · 2023: 81 · 2022: 92 · 2021: 117 · 2020: 106 · 2019: 103 · 2018: 97 · 2017: 90 · 2016: 121 · 2015: 83 · 2014: 39
FWCI: 89.27
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Funders: American Diabetes Association
Bristol-Myers Squibb
Eli Lilly and Company
AstraZeneca
Sanofi
Novo Nordisk
Astellas Pharma
Daiichi Sankyo Europe
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: SGLT2 inhibitors, empagliflozin, type 2 diabetes, glycosuria, endogenous glucose production, glucose oxidation, nonoxidative glucose disposal, lipid oxidation, beta-cell glucose sensitivity, glucagon response, insulin response, glucose metabolism, indirect calorimetry, mixed meal tolerance, urinary glucose excretion, glucose homeostasis
MeSH terms: Sodium-Glucose Transporter 2 Inhibitors, Aged, Benzhydryl Compounds, Blood Glucose, Calorimetry, Diabetes Mellitus, Type 2, Female, Glucose, Glucosides, Glycosuria, Glycated Hemoglobin, Humans, Insulin, Male, Metformin, Middle Aged, Oxygen, Body Mass Index, Postprandial Period, Area Under Curve, Insulin-Secreting Cells, Sodium-Glucose Transporter 2

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Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients

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