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Elian, V.; Popovici, V.; Karampelas, O.; Pircalabioru, G.G.; Radulian, G.; Musat, M. SGLT-2 Inhibitors in Diabetes Mellitus Therapy. Encyclopedia. Available online: https://encyclopedia.pub/entry/55338 (accessed on 23 April 2024).
Elian V, Popovici V, Karampelas O, Pircalabioru GG, Radulian G, Musat M. SGLT-2 Inhibitors in Diabetes Mellitus Therapy. Encyclopedia. Available at: https://encyclopedia.pub/entry/55338. Accessed April 23, 2024.
Elian, Viviana, Violeta Popovici, Oana Karampelas, Gratiela Gradisteanu Pircalabioru, Gabriela Radulian, Madalina Musat. "SGLT-2 Inhibitors in Diabetes Mellitus Therapy" Encyclopedia, https://encyclopedia.pub/entry/55338 (accessed April 23, 2024).
Elian, V., Popovici, V., Karampelas, O., Pircalabioru, G.G., Radulian, G., & Musat, M. (2024, February 22). SGLT-2 Inhibitors in Diabetes Mellitus Therapy. In Encyclopedia. https://encyclopedia.pub/entry/55338
Elian, Viviana, et al. "SGLT-2 Inhibitors in Diabetes Mellitus Therapy." Encyclopedia. Web. 22 February, 2024.
SGLT-2 Inhibitors in Diabetes Mellitus Therapy
Edit

The primary treatment for autoimmune Diabetes Mellitus (Type 1 Diabetes Mellitus-T1DM) is insulin therapy. Unfortunately, a multitude of clinical cases has demonstrated that the use of insulin as a sole therapeutic intervention fails to address all issues comprehensively. Therefore, non-insulin adjunct treatment has been investigated and shown successful results in clinical trials. Various hypoglycemia-inducing drugs such as Metformin, glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, amylin analogs, and Sodium-Glucose Cotransporters 2 (SGLT-2) inhibitors, developed good outcomes in patients with T1DM. SGLT-2 inhibitors have remarkably improved the treatment of patients with diabetes by preventing cardiovascular events, heart failure hospitalization, and progression of renal disease. However, their pharmacological potential has not been explored enough. 

SGLT-2 inhibitors Type 1 diabetes mellitus automated insulin delivery systems

1. Introduction

Due to considerable glycemic and non-glycemic benefits, the FDA approved several selective SGLT-2 inhibitors for T2DM treatment [1]. Currently, all available gliflozins as drugs commercialized in pharmacies (Canagliflozin, Dapagliflozin, Empagliflozin, Ertugliflozin, and Bexagliflozin) have T2DM as a main common indication. Heart failure (HF) is mentioned for Dapagliflozin and Empagliflozin, and chronic kidney disease (CKD) only for Dapagliflozin.
Sotagliflozin, a dual SGLT-1/2 inhibitor, is the only representative officially indicated in T1DM.
Other new similar compounds (Ipragliflozin, Luseogliflozin, Tofogliflozin, and Remogliflozin) are investigated in clinical studies. The most recent SGLT inhibitors are investigated using pharmacokinetic and pharmacodynamic analyses (Remoglicoflozin [2][3][4][5], Henaglicoflozin [6][7][8][9], and Licoglicoflozin [10][11][12][13]).
All data are summarized in Table 1.
Table 1. FDA-approved/in-trials SGLT-2 Inhibitors for T2DM therapy.
SGLT-2
Inhibitor
Active
Ingredient(s)
Daily Dose
(mg)
Brand Name Company
Selective SGLT-2 Inhibitors
Canagliflozin
[14][15][16]
Canagliflozin 100 Invokana Janssen-Cilag
International NV
Beerse, Belgium
Canagliflozin + Metformin 50/500
50/1000
150/500
150/1000
Invokamet
Canagliflozin + Metformin extended-release Invokamet XR
Dapagliflozin
[17][18][19][20][21]
Dapagliflozin 5
10
Forxiga AstraZeneca AB
Södertälje
Sweden
Dapagliflozin + Metformin
extended-release
5/1000
5/850
Xigduo XR
Dapagliflozin + Saxagliptin 5/10 Qtern
Empagliflozin
[22][23][24][25]
Empagliflozin 10
25
Jardiance Boehringer Ingelheim International GmbH
Ingelheim am Rhein,
Germany
Empagliflozin + Linagliptin 10/5
25/5
Glyxambi
Empagliflozin + Metformin 5/1000
5/850
12.5/1000
12.5/850
Synjardy
Empagliflozin + Metformin
extended-release
25/1000 Synjardy XR
Ertugliflozin
[26][27]
Ertugliflozin 5
15
Steglatro Merck Sharp & Dohme
Haarlem,
Netherland
Ertugliflozin + Metformin 2.5/850
7.5/850
Segluromet
Ertugliflozin + Sitagliptin 5/100
15/100
Steglujan
Bexagliflozin
[28][29][30][31][32][33]
Bexagliflozin 20 Brenzavvy TheracosBio, LLC
Marlborough, MA, USA
Ipragliflozin
[34][35][36][37][38]
Ipragliflozin 25
50
Suglat Astellas Pharma LTD,
Addlestone, UK
Luseogliflozin
[39][40][41][42][43][44]
Luseogliflozin 2.5
5
Lusefi Taisho Pharmaceutical Holdings Co., Ltd.,
Tokyo, Japan
Tofogliflozin
[45][46][47]
Tofogliflozin 20
40
Apleway Chugai Pharmaceutical Co., Ltd.,
Tokyo, Japan
Remogliflozin
[3][4][5][48][49]
Remogliflozin 100 Remogliflozin
etabonate
GlaxoSmithKline plc, Brentford, UK
Glenmark Pharmceuticals Ltd.,
Mumbai, India
Henagliflozin
[6][7][8][50][51]
Henagliflozin 5
10
SHR3824 Jiangsu Hengrui Pharmaceuticals Co., Ltd.,
Lianyungang,
China
Dual SGLT-2 + SGLT-1 Inhibitors
Sotagliflozin
[52][53][54][55][56][57][58][59][60]
Sotagliflozin 200
400
Zynquista
Inpefa
Lexicon
Pharmaceuticals, Inc.,
The Woodlands, TX, USA
Licogliflozin
[10][11][12][13][61]
Licogliflozin No data LIK-066 Novartis AG
Basel, Switzerland

2. Benefits of SGLT-2 Inhibitors

Globally, SGLT-2 inhibitors are approximately the most prescribed oral antidiabetic drugs. Their beneficial effects beyond glycemic control include weight loss, protection against major cardiovascular events, blood pressure reduction, and delaying the progression of chronic kidney disease (CKD).

2.1. Weight Loss

SGLT-2i directly reduces body weight by removing glucose through urine, thus increasing calorie loss. Glycosuria due to the SGLT-2 inhibitors leads to lower plasma glucose and insulin levels, followed by increased fasting and post-meal glucagon concentration. While blood glucose concentration is diminished, lipid storage is mobilized to be used as an energy substrate. The persistent excretion of glucose in urine induces increasing gluconeogenesis, suppresses tissue glucose disposal and glucose oxidation, accelerates lipolysis and fat oxidation, and enhances ketogenesis. The overall result of these metabolic changes resembles a fasting state, which will cause the loss of fat mass and weight in the long run [62]. Another study shows the concomitance of weight loss and Hemoglobin A1c level diminution during the therapy with SGLT-2is [63]. Thus, sodium-glucose cotransporter inhibitors could be called mimic-fasting medication to prevent cardiovascular complications [64][65]. SGLT-2 inhibitors reduce body weight by around 2–4 kg; this average is constant for all representatives and persists for up to 4 years [62].

2.2. Heart Protection

Renal function improvement and preservation through hemodynamic and nonhemodynamic mechanisms are essential for SGLT-2 inhibitors in heart protection [66]. It is necessary to know the interactions between all biochemical processes, the chronology of all changes, and their correlation with the cardiovascular benefits of gliflozin therapy [67]. The potential mechanisms [68] are diuresis and natriuresis, changes in myocardial energetics, increased erythropoietin (EPO) production and erythropoiesis, changes in reno-cardiac signaling, inhibition of the sympathetic nervous system, inhibition of the Na+/H+ Exchanger-1 (NHE1), inhibition of the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome, potential vascular effects, and reducing uric acid levels in serum [69].

2.3. Kidney Protection

The highlight of SGLT-2i kidney protection led to significant interest in gliflozins’ broader applications in CKD therapy [70]. The potential mechanisms of their protective effects could be glucosuria, inducing natriuresis and osmotic diuresis and leading to reduced plasma volume and lower blood pressure, reducing proteinuria, and delaying CKD progression in patients with albuminuria [71], hemodynamic changes at the systemic and glomerular levels, metabolic pathway, and decreasing oxidative stress and inflammation.

3. Adverse Effects of SGLT-2 Inhibitors

3.1. Acute Kidney Injury (AKI)

The SGLT-2is induces glucose and sodium overexcretion, conducting osmotic diuresis. It may lead to hyperosmolarity and dehydration, increasing the risk of AKI [72]. Recent studies rigorously demonstrate that SGLT-2 inhibitors are safe for the kidneys and do not predispose to AKI [73].

3.2. Polyuria

Significant glucosuria and natriuria induced by SGLT-2is lead to polyuria due to osmotic diuresis.

3.3. Euglycemic Diabetic Ketoacidosis (DKA)

Production of ketone bodies may show a dual face. The heart and brain can rapidly use them as energetic substrates, avoiding the accumulation of fatty acid or glucose metabolites. Normal ketone levels are <0.6 mmol/L. Most patients treated with SGLT-2is concomitantly have ketosis (ketone levels are slightly increased 0.6–1.5 mmol/L), and they do not develop ketoacidosis. Thus, the tendency toward ketosis can be augmented by a low-carb intake in patients who are trying to lose weight. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy, generally occurring in glucose-limiting conditions. Elevated blood levels of acetoacetate (AA), 3-β-hydroxybutyrate (BHB), and acetone are known as hyperketonemia. BHB serum concentration increases after fasting but should not exceed 0.4 mmol/L. High levels of circulating ketones are linked to oxidative stress and numerous morbid conditions.
The risk of DKA is 1.5–3 mmol/L. DKA manifests when the ketone level is highly increased, over 3 mmol/L. Possible mechanisms [72] of SGLT-2 inhibitors associated with euglycemic DKA could be noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion.

3.4. Genito-Urinary Tract Infections

Glycosuria is the main factor implied in these infectious diseases, being a favorable medium for the growth of bacterial and fungal strains. They are more frequent in females and can be easily treated with non-expensive drugs.

3.5. Bone Fractures and Amputation Risk

Potential mechanisms for fractures [74] could be volume contraction leading to dizziness and falls, possible effects on calcium, phosphate, and vitamin D homeostasis, and reduction in bone mineral density. The amputation risk [75] is linked to peripheral vascular disease, neuropathy, history of diabetic foot ulcer, and previous history of amputations. Euglycemic DKA and its potential association with a significant risk for lower-extremity amputation represent sporadic but possible fatal adverse events of SGLT-2is. Some studies reported that SGLT-2 inhibitors in T2DM may cause latent autoimmune DM of adulthood (LADA) [76].

4. SGLT-2 Inhibitors in the Therapy of DM Complications and Comorbidities

Despite the common knowledge that DM is associated with most known complications (traditional complications such as stroke, coronary heart disease, and heart failure, peripheral neuropathy, retinopathy, diabetic kidney disease), an increased prevalence of cardiovascular pathology and a group of lesser-studied ones have been reported (cancer, infections, functional and cognitive disability, liver disease and affective disorders) [77].
The benefits of SGLT-2 inhibitors in DM complications and comorbidities could be explained through the dual redox behavior of gliflozins (Figure 1) because oxidative stress has an essential role in their onset and harmful evolution. High blood glucose levels induce ROS production, leading to overexpression of the SGLT-2 in tubular cells, exacerbating oxidative stress. SGLT-2is has demonstrated clear cardiovascular and renal protection due to its antioxidant properties. Severe systemic comorbidity that involves the whole body, leading to functional decline and harmful outcomes [78][79][80] is frailty [81][82][83][84][85][86][87] or functional disability [88][89][90][91], and its management is still debated [86][87]. SGLT-2i positively acts on cardiovascular complications, especially on the HF rehospitalization rate [92], during several potential mechanisms: improving cardiovascular energetics, reducing vascular tone and blood pressure, decreasing systemic inflammation, atheroprotective effects, reduction of vascular damage, and direct neuroprotective mechanisms (acetylcholinesterase inhibition and increase in cerebral levels of brain-derived neurotrophic factor). All benefits could be maintained through rigorous balancing between oxidant and antioxidant processes [93].
Figure 1. SGLT-2 inhibitors’ therapeutic potential in DM complications and comorbidities: cardiovascular diseases, nephropathy, liver diseases, neural disorders, and cancers—reproduction with permission from [94].
The anticancer potential of gliflozins depends on the blood glucose-lowering capacity [95][96]. SGLT-2 inhibitors induce apoptosis and DNA damage, reducing cancer cell proliferation [97][98][99][100][101][102][103][104] through mitochondrial membrane instability metabolic changes (oxidative phosphorylation, DNA synthesis, glycolysis, ATP and fatty acids level diminution, beta-oxidation, and ketone amount augmentation).
DM is also associated with cancer development through a complex mechanism. Treatment with SGLT-2 inhibitors can diminish the risk of cancer incidence in DM patients [105] because gliflozins have anticancer activity through various mechanisms, as previously shown [106][107][108][109][110][111][112]. Moreover, SGLT-2 inhibitors can protect DM patients against the cardiotoxic action of anticancer drugs [68].

5. DM Patient Adherence to SGLT-2is Therapy

The most common reasons for discontinuing treatment with SGLT-2is are frequent urination, genital infection, improved glycemic control, and renal dysfunction. A recent retrospective study [113] did not find a correlation between patients’ compliance and DM type, duration, diabetic control, renal function, or DM complications of diabetes in both groups. Only the age was correlated (the adherence negatively correlates with the patient’s age).

References

  1. Agrawal, P.; Pursnani, N.; Gautam, A.; Garg, R. Is REmogliflozin an Effective Drug in MANaging Type-2 Diabetes Mellitus: A Comparative Study—(REDMAN). Diabetes Epidemiol. Manag. 2022, 7, 100076.
  2. Dobbins, R.; Hussey, E.K.; O’Connor-Semmes, R.; Andrews, S.; Tao, W.; Wilkison, W.O.; Cheatham, B.; Sagar, K.; Hanmant, B. Assessment of Safety and Tolerability of Remogliflozin Etabonate (GSK189075) When Administered with Total Daily Dose of 2000 Mg of Metformin. BMC Pharmacol. Toxicol. 2021, 22, 34.
  3. Attimarad, M.; Venugopala, K.N.; Nair, A.B.; Sreeharsha, N.; Deb, P.K. Experimental Design Approach for Quantitative Expressions of Simultaneous Quantification of Two Binary Formulations Containing Remogliflozin and Gliptins by RP-HPLC. Separations 2022, 9, 23.
  4. Jain, R.; Bhavatharini, N.; Saravanan, T.; Seshiah, V.; Jain, N. Use of Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitor Remogliflozin and Possibility of Acute Kidney Injury in Type-2 Diabetes. Cureus 2022, 14, e32573.
  5. Que, L.; Huang, K.; Xiang, X.; Ding, Y.; Chu, N.; He, Q. No Apparent Pharmacokinetic Interactions Were Found between Henagliflozin: A Novel Sodium-glucose Co-transporter 2 Inhibitor and Glimepiride in Healthy Chinese Male Subjects. J. Clin. Pharm. Ther. 2022, 47, 1225–1231.
  6. He, X.; Liu, G.; Chen, X.; Wang, Y.; Liu, R.; Wang, C.; Huang, Y.; Shen, J.; Jia, Y. Pharmacokinetic and Pharmacodynamic Interactions Between Henagliflozin, a Novel Selective SGLT-2 Inhibitor, and Warfarin in Healthy Chinese Subjects. Clin. Ther. 2023, 45, 655–661.
  7. Lu, J.; Fu, L.; Li, Y.; Geng, J.; Qin, L.; Li, P.; Zheng, H.; Sun, Z.; Li, Y.; Zhang, L.; et al. Henagliflozin Monotherapy in Patients with Type 2 Diabetes Inadequately Controlled on Diet and Exercise: A Randomized, Double-blind, Placebo-controlled, Phase 3 Trial. Diabetes Obes. Metab. 2021, 23, 1111–1120.
  8. Zhang, Y.; Liu, Y.; Yu, C.; Wang, Y.; Zhan, Y.; Liu, H.; Zou, J.; Jia, J.; Chen, Q.; Zhong, D. Tolerability, Pharmacokinetic, and Pharmacodynamic Profiles of Henagliflozin, a Novel Selective Inhibitor of Sodium-Glucose Cotransporter 2, in Healthy Subjects Following Single- and Multiple-Dose Administration. Clin. Ther. 2021, 43, 396–409.
  9. Zaki, A.M.; Abo-Elnour, D.E.; Abdalla, Y.E.; Hassan, R.Y.; Salama, M.K.; Elboraay, T.; Abdelhaleem, I.A. Dose-Dependent Efficacy and Safety of Licogliflozin on Obese Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Diabetes Metab. Syndr. Clin. Res. Rev. 2022, 16, 102657.
  10. De Boer, R.A.; Núñez, J.; Kozlovski, P.; Wang, Y.; Proot, P.; Keefe, D. Effects of the Dual Sodium–Glucose Linked Transporter Inhibitor, Licogliflozin vs. Placebo or Empagliflozin in Patients with Type 2 Diabetes and Heart Failure. Br. J. Clin. Pharmacol. 2020, 86, 1346–1356.
  11. Tan, S.; Ignatenko, S.; Wagner, F.; Dokras, A.; Seufert, J.; Zwanziger, D.; Dunschen, K.; Zakaria, M.; Huseinovic, N.; Basson, C.T.; et al. Licogliflozin versus Placebo in Women with Polycystic Ovary Syndrome: A Randomized, Double-blind, Phase 2 Trial. Diabetes Obes. Metab. 2021, 23, 2595–2599.
  12. He, Y.; Haynes, W.; Meyers, C.D.; Amer, A.; Zhang, Y.; Mahling, P.; Mendonza, A.E.; Ma, S.; Chutkow, W.; Bachman, E. The Effects of Licogliflozin, a Dual SGLT1/2 Inhibitor, on Body Weight in Obese Patients with or without Diabetes. Diabetes Obes. Metab. 2019, 21, 1311–1321.
  13. EMA. Canagliflozin Summary of Product Characteristics. Available online: https://www.ema.europa.eu/en/medicines/human/EPAR/invokana (accessed on 1 December 2023).
  14. Rodbard, H.W.; Peters, A.L.; Slee, A.; Cao, A.; Traina, S.B.; Alba, M. The Effect of Canagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, on Glycemic End Points Assessed by Continuous Glucose Monitoring and Patient-Reported Outcomes Among People with Type 1 Diabetes. Diabetes Care 2017, 40, 171–180.
  15. Taieb, V.; Pacou, M.; Schroeder, M.; Nielsen, A.T.; Neslusan, C.; Schubert, A. Bayesian Network Meta-Analysis to Assess the Relative Efficacy and Safety of Canagliflozin in Patients with Type 2 Diabetes Mellitus (T2DM) Inadequately Controlled on Metformin and Sulphonylurea (MET+SU). Value Health 2013, 16, PDB5.
  16. EMA. Dapagliflozin Summary of Product Characteristics. Available online: https://www.ema.europa.eu/en/medicines/human/EPAR/forxiga (accessed on 25 September 2023).
  17. Adamson, C.; Docherty, K.F.; Heerspink, H.J.L.; de Boer, R.A.; Damman, K.; Inzucchi, S.E.; Køber, L.; Kosiborod, M.N.; Martinez, F.A.; Petrie, M.C.; et al. Initial Decline (Dip) in Estimated Glomerular Filtration Rate After Initiation of Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction: Insights From DAPA-HF. Circulation 2022, 146, 438–449.
  18. NCT05162690; Efficacy of Dapagliflozin in Diabetes Associated Peripheral Neuropathy. Postgraduate Institute of Medical Education and Research: Chandigarh, India, 2021. Available online: https://clinicaltrials.gov/show/NCT05162690 (accessed on 20 October 2023).
  19. Palandurkar, G.; Kumar, S. Current Status of Dapagliflozin in Congestive Heart Failure. Cureus 2022, 14, e29413.
  20. Colombo, G.; Casella, R.; Cazzaniga, A.; Casiraghi, C. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. Intern. Emerg. Med. 2020, 15, 515–517.
  21. EMA. Empagliflozin Summary of Product Characteristics. Available online: https://www.ema.europa.eu/en/medicines/human/EPAR/jardiance (accessed on 20 November 2023).
  22. Bteich, F.; Daher, G.; Kapoor, A.; Charbek, E.; Kamel, G. Post-Surgical Euglycemic Diabetic Ketoacidosis in a Patient on Empagliflozin in the Intensive Care Unit. Cureus 2019, 11, e4496.
  23. Jigheh, Z.A.; Haghjo, A.G.; Argani, H.; Roshangar, L.; Rashtchizadeh, N.; Sanajou, D.; Ahmad, S.N.S.; Rashedi, J.; Dastmalchi, S.; Abbasi, M.M. Empagliflozin Alleviates Renal Inflammation and Oxidative Stress in Streptozotocin-Induced Diabetic Rats Partly by Repressing HMGB1-TLR4 Receptor Axis. Iran. J. Basic Med. Sci. 2019, 22, 384–390.
  24. Baer, P.C.; Koch, B.; Freitag, J.; Schubert, R.; Geiger, H. No Cytotoxic and Inflammatory Effects of Empagliflozin and Dapagliflozin on Primary Renal Proximal Tubular Epithelial Cells under Diabetic Conditions In Vitro. Int. J. Mol. Sci. 2020, 21, 391.
  25. Zhang, F.; Wang, W.; Hou, X. Effectiveness and Safety of Ertugliflozin for Type 2 Diabetes: A Meta-analysis of Data from Randomized Controlled Trials. J. Diabetes Investig. 2022, 13, 478–488.
  26. EMA. Ertugliflozin Summary of Product Characteristics. Available online: https://www.ema.europa.eu/en/documents/product-information/steglatro-epar-product-information_en.pdf (accessed on 25 November 2023).
  27. Hoy, S.M. Bexagliflozin: First Approval. Drugs 2023, 83, 447–453.
  28. Hadd, M.J.; Bienhoff, S.E.; Little, S.E.; Geller, S.; Ogne-Stevenson, J.; Dupree, T.J.; Scott-Moncrieff, J.C. Safety and Effectiveness of the Sodium-glucose Cotransporter Inhibitor Bexagliflozin in Cats Newly Diagnosed with Diabetes Mellitus. J. Vet. Intern. Med. 2023, 37, 915–924.
  29. Pasqualotto, E.; Figueiredo Watanabe, J.M.; Gewehr, D.M.; da Silva Maintinguer, R.; van de Sande-Lee, S.; de Araujo, G.N.; Leal, F.S.; Pinheiro, C.E.A. Efficacy and Safety of Bexagliflozin in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis. Diabetes Obes. Metab. 2023, 25, 1794–1802.
  30. Halvorsen, Y.; Walford, G.; Thurber, T.; Russell, H.; Massaro, M.; Freeman, M.W. A 12-week, Randomized, Double-blind, Placebo-controlled, Four-arm Dose-finding Phase 2 Study Evaluating Bexagliflozin as Monotherapy for Adults with Type 2 Diabetes. Diabetes Obes. Metab. 2020, 22, 566–573.
  31. Halvorsen, Y.; Conery, A.L.; Lock, J.P.; Zhou, W.; Freeman, M.W. Bexagliflozin as an Adjunct to Metformin for the Treatment of Type 2 Diabetes in Adults: A 24-week, Randomized, Double-blind, Placebo-controlled Trial. Diabetes Obes. Metab. 2023, 25, 2954–2962.
  32. Halvorsen, Y.; Lock, J.P.; Zhou, W.; Zhu, F.; Freeman, M.W. A 24-week, Randomized, Double-blind, Active-controlled Clinical Trial Comparing Bexagliflozin with Sitagliptin as an Adjunct to Metformin for the Treatment of Type 2 Diabetes in Adults. Diabetes Obes. Metab. 2019, 21, 2248–2256.
  33. Tanaka, M.; Yamakage, H.; Inoue, T.; Odori, S.; Kusakabe, T.; Shimatsu, A.; Satoh-Asahara, N. Beneficial Effects of Ipragliflozin on the Renal Function and Serum Uric Acid Levels in Japanese Patients with Type 2 Diabetes: A Randomized, 12-Week, Open-Label, Active-Controlled Trial. Intern. Med. 2020, 59, 601–609.
  34. Takasu, T.; Yokono, M.; Tahara, A.; Takakura, S. In Vitro Pharmacological Profile of Ipragliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor. Biol. Pharm. Bull. 2019, 42, 507–511.
  35. Morishita, A.; Tadokoro, T.; Fujihara, S.; Iwama, H.; Oura, K.; Fujita, K.; Tani, J.; Takuma, K.; Nakahara, M.; Shi, T.; et al. Ipragliflozin Attenuates Non-Alcoholic Steatohepatitis Development in an Animal Model. PLoS ONE 2022, 17, e0261310.
  36. Yamauchi, Y.; Nakamura, A.; Takahashi, K.; Takase, T.; Yamamoto, C.; Yokota, I.; Atsumi, T.; Miyoshi, H. Factors with Remission of Fatty Liver in Patients with Type 2 Diabetes Treated with Ipragliflozin. Endocr. J. 2019, 66, 995–1000.
  37. Kashiwagi, A.; Shestakova, M.V.; Ito, Y.; Noguchi, M.; Wilpshaar, W.; Yoshida, S.; Wilding, J.P.H. Safety of Ipragliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Phase II/III/IV Clinical Trials. Diabetes Therapy 2019, 10, 2201–2217.
  38. Bando, S.; Ichikawa, R.; Taguchi, T.; Fujimoto, K.; Motomiya, T.; Taguchi, M.; Takano, K.; Shichiri, M.; Miyatsuka, T. Effects of Luseogliflozin on the Secretion of Islet Hormones and Incretins in Patients with Type 2 Diabetes. Endocr. J. 2022, 69, 681–687.
  39. Ejiri, K.; Miyoshi, T.; Kihara, H.; Hata, Y.; Nagano, T.; Takaishi, A.; Toda, H.; Nanba, S.; Nakamura, Y.; Akagi, S.; et al. Effect of Luseogliflozin on Heart Failure with Preserved Ejection Fraction in Patients With Diabetes Mellitus. J. Am. Heart Assoc. 2020, 9, e015103.
  40. Nakashima, M.; Miyoshi, T.; Ejiri, K.; Kihara, H.; Hata, Y.; Nagano, T.; Takaishi, A.; Toda, H.; Nanba, S.; Nakamura, Y.; et al. Effects of Luseogliflozin on Estimated Plasma Volume in Patients with Heart Failure with Preserved Ejection Fraction. ESC Heart Fail. 2022, 9, 712–720.
  41. Kario, K.; Okada, K.; Murata, M.; Suzuki, D.; Yamagiwa, K.; Abe, Y.; Usui, I.; Tsuchiya, N.; Iwashita, C.; Harada, N.; et al. Effects of Luseogliflozin on Arterial Properties in Patients with Type 2 Diabetes Mellitus: The Multicenter, Exploratory LUSCAR Study. J. Clin. Hypertens. 2020, 22, 1585–1593.
  42. Osaka, N.; Mori, Y.; Terasaki, M.; Hiromura, M.; Saito, T.; Yashima, H.; Shiraga, Y.; Kawakami, R.; Ohara, M.; Fukui, T.; et al. Luseogliflozin Inhibits High Glucose-Induced TGF- β 2 Expression in Mouse Cardiomyocytes by Suppressing NHE-1 Activity. J. Int. Med. Res. 2022, 50, 030006052210974.
  43. Chino, Y.; Kuwabara, M.; Hisatome, I. Factors Influencing Change in Serum Uric Acid After Administration of the Sodium-Glucose Cotransporter 2 Inhibitor Luseogliflozin in Patients with Type 2 Diabetes Mellitus. J. Clin. Pharmacol. 2022, 62, 366–375.
  44. Katakami, N.; Mita, T.; Yoshii, H.; Shiraiwa, T.; Yasuda, T.; Okada, Y.; Torimoto, K.; Umayahara, Y.; Kaneto, H.; Osonoi, T.; et al. Effect of Tofogliflozin on Arterial Stiffness in Patients with Type 2 Diabetes: Prespecified Sub-Analysis of the Prospective, Randomized, Open-Label, Parallel-Group Comparative UTOPIA Trial. Cardiovasc. Diabetol. 2021, 20, 4.
  45. Kawaguchi, Y.; Sawa, J.; Kumeda, Y. Efficacy and Safety of Tofogliflozin and Ipragliflozin for Patients with Type-2 Diabetes: A Randomized Crossover Study by Flash Glucose Monitoring. Diabetes Ther. 2020, 11, 2945–2958.
  46. Utsunomiya, K.; Kakiuchi, S.; Senda, M.; Fujii, S.; Kurihara, Y.; Gunji, R.; Koshida, R.; Kameda, H.; Tamura, M.; Kaku, K. Safety and Effectiveness of Tofogliflozin in Japanese Patients with Type 2 Diabetes Mellitus: Results of 24-month Interim Analysis of a Long-term Post-marketing Study (J-STEP/LT). J. Diabetes Investig. 2020, 11, 906–916.
  47. Markham, A. Remogliflozin Etabonate: First Global Approval. Drugs 2019, 79, 1157–1161.
  48. Napolitano, A.; Miller, S.; Murgatroyd, P.R.; Hussey, E.; Dobbins, R.L.; Bullmore, E.T.; Nunez, D.J.R. Exploring Glycosuria as a Mechanism for Weight and Fat Mass Reduction. A Pilot Study with Remogliflozin Etabonate and Sergliflozin Etabonate in Healthy Obese Subjects. J. Clin. Transl. Endocrinol. 2014, 1, e3–e8.
  49. Ding, L.; Liu, S.; Yan, H.; Li, Z.; Zhou, Y.; Pang, H.; Lu, R.; Zhang, W.; Che, M.; Wang, L.; et al. Pharmacokinetics of Henagliflozin in Dialysis Patients with Diabetes. Clin. Pharmacokinet. 2023, 62, 1581–1587.
  50. Chen, Z.; Li, L.; Zhan, Y.; Zhang, Y.; Liu, H.; Zou, J.; Zhong, D. Characterization and Quantitative Determination of Henagliflozin Metabolites in Humans. J. Pharm. Biomed. Anal. 2021, 192, 113632.
  51. EMA. Zynquista, Summary of Product Characteristics. Available online: https://www.ema.europa.eu/en/medicines/human/EPAR/zynquista (accessed on 30 November 2023).
  52. Pérez, M.S.; Rodríguez-Capitán, J.; Requena-Ibáñez, J.A.; Santos-Gallego, C.G.; Urooj Zafar, M.; Escolar, G.; Mancini, D.; Mitter, S.; Lam, D.; Contreras, J.P.; et al. Rationale and Design of the SOTA-P-CARDIA Trial (ATRU-V): Sotagliflozin in HFpEF Patients Without Diabetes. Cardiovasc. Drugs Ther. 2023.
  53. Markham, A.; Keam, S.J. Sotagliflozin: First Global Approval. Drugs 2019, 79, 1023–1029.
  54. Cefalo, C.M.A.; Cinti, F.; Moffa, S.; Impronta, F.; Sorice, G.P.; Mezza, T.; Pontecorvi, A.; Giaccari, A. Sotagliflozin, the First Dual SGLT Inhibitor: Current Outlook and Perspectives. Cardiovasc. Diabetol. 2019, 18, 20.
  55. Sands, A.T.; Zambrowicz, B.P.; Rosenstock, J.; Lapuerta, P.; Bode, B.W.; Garg, S.K.; Buse, J.B.; Banks, P.; Heptulla, R.; Rendell, M.; et al. Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes. Diabetes Care 2015, 38, 1181–1188.
  56. Sotagliflozin (Inpefa) for Heart Failure. Med. Lett. Drugs Ther. 2023, 65, 114–116.
  57. Davies, M.J.; Sun, F.; Banks, P.; Bhatt, D.L.; Pitt, B. Major Adverse Cardiovascular Events Across the Sotagliflozin Clinical Development Program. Am. Heart J. 2022, 254, 243–244.
  58. Bhatt, D.L.; Szarek, M.; Steg, P.G.; Cannon, C.P.; Leiter, L.A.; McGuire, D.K.; Lewis, J.B.; Riddle, M.C.; Voors, A.A.; Metra, M.; et al. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N. Engl. J. Med. 2021, 384, 117–128.
  59. Sims, H.; Smith, K.H.; Bramlage, P.; Minguet, J. Sotagliflozin: A Dual Sodium-Glucose Co-Transporter-1 and -2 Inhibitor for the Management of Type 1 and Type 2 Diabetes Mellitus. Diabet. Med. 2018, 35, 1037–1048.
  60. Wang-Lakshman, L.; Mendonza, A.E.; Huber, R.; Walles, M.; He, Y.; Jarugula, V. Pharmacokinetics, Metabolism, and Excretion of Licogliflozin, a Dual Inhibitor of SGLT1/2, in Rats, Dogs, and Humans. Xenobiotica 2021, 51, 413–426.
  61. Feder, D.; de Fatima Veiga Gouveia, M.R.; Govato, T.C.P.; Nassis, C.D.Z. SGLT2 Inhibitors and the Mechanisms Involved in Weight Loss. Curr. Pharmacol. Rep. 2020, 6, 346–353.
  62. Kaur, P.; Kotru, S.; Tuteja, L.; Ludhiadch, A.; Munshi, A. Role of SGLT2 Inhibitors in Diabetes Management: Focus on HbA1c Levels, Weight Loss and Genetic Variation. J. Med. Health Stud. 2023, 4, 187–196.
  63. Giaccari, A. Sodium-glucose Co-transporter Inhibitors: Medications That Mimic Fasting for Cardiovascular Prevention. Diabetes Obes. Metab. 2019, 21, 2211–2218.
  64. Janež, A.; Fioretto, P. SGLT2 Inhibitors and the Clinical Implications of Associated Weight Loss in Type 2 Diabetes: A Narrative Review. Diabetes Ther. 2021, 12, 2249–2261.
  65. Vallon, V.; Verma, S. Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function. Annu. Rev. Physiol. 2021, 83, 503–528.
  66. Pereira, M.J.; Eriksson, J.W. Emerging Role of SGLT-2 Inhibitors for the Treatment of Obesity. Drugs 2019, 79, 219–230.
  67. Vaziri, Z.; Saleki, K.; Aram, C.; Alijanizadeh, P.; Pourahmad, R.; Azadmehr, A.; Ziaei, N. Empagliflozin Treatment of Cardiotoxicity: A Comprehensive Review of Clinical, Immunobiological, Neuroimmune, and Therapeutic Implications. Biomed. Pharmacother. 2023, 168, 115686.
  68. Somagutta, M.K.R.; Luvsannyam, E.; Jain, M.; Cuddapah, G.V.; Pelluru, S.; Mustafa, N.; Nasereldin, D.S.; Pendyala, S.K.; Jarapala, N.; Padamati, B. Sodium Glucose Co-Transport 2 Inhibitors for Gout Treatment. Discoveries 2022, 10, e152.
  69. Dharia, A.; Khan, A.; Sridhar, V.S.; Cherney, D.Z.I. SGLT2 Inhibitors: The Sweet Success for Kidneys. Annu. Rev. Med. 2023, 74, 369–384.
  70. Kalay, Z.; Sahin, O.E.; Copur, S.; Danacı, S.; Ortiz, A.; Yau, K.; Cherney, D.Z.I.; Kanbay, M. SGLT-2 Inhibitors in Nephrotic-Range Proteinuria: Emerging Clinical Evidence. Clin. Kidney J. 2023, 16, 52–60.
  71. Hahn, K.; Ejaz, A.A.; Kanbay, M.; Lanaspa, M.A.; Johnson, R.J. Acute Kidney Injury from SGLT2 Inhibitors: Potential Mechanisms. Nat. Rev. Nephrol. 2016, 12, 711–712.
  72. Copur, S.; Yildiz, A.; Basile, C.; Tuttle, K.R.; Kanbay, M. Is There Any Robust Evidence Showing That SGLT2 Inhibitor Use Predisposes to Acute Kidney Injury? J. Nephrol. 2022, 36, 31–43.
  73. Halimi, S.; Vergès, B. Adverse Effects and Safety of SGLT-2 Inhibitors. Diabetes Metab. 2014, 40, S28–S34.
  74. Qiu, M.; Ding, L.-L.; Zhang, M.; Zhou, H.-R. Safety of Four SGLT2 Inhibitors in Three Chronic Diseases: A Meta-Analysis of Large Randomized Trials of SGLT2 Inhibitors. Diab Vasc. Dis. Res. 2021, 18, 147916412110110.
  75. Kao, C.-T.; Lee, Y.J.; Al-Battah, H. Eugylcemic Diabetic Ketoacidosis: An Atypical Presentation of Latent Autoimmune Diabetes in Adults (LADA) with Concurrent SGLT2-Inhibitor Use. In Proceedings of the C44. Critical Care Case Reports: Metabolic, Renal, And Endocrine, Philadelphia, PA, USA, 15–20 May 2020; American Thoracic Society International Conference: New York, NY, USA, 2020; p. A5167.
  76. Tomic, D.; Shaw, J.E.; Magliano, D.J. The Burden and Risks of Emerging Complications of Diabetes Mellitus. Nat. Rev. Endocrinol. 2022, 18, 525–539.
  77. Zhang, Q.; Wu, Y.; Lu, Y.; Fei, X. Efficacy and Safety of Metformin and Sodium-Glucose Co-Transporter-2 Inhibitors in Adults with Type 1 Diabetes: A Systematic Review and Network Meta-Analysis. Rev. Clínica Española 2020, 220, 8–21.
  78. Şahin, S.; Haliloğlu, Ö.; Polat Korkmaz, Ö.; Durcan, E.; Rekali Şahin, H.; Yumuk, V.D.; Damci, T.; Ilkova, H.; Oşar Siva, Z. Does Treatment with Sodium-Glucose Co-Transporter-2 Inhibitors Have an Effect on Sleep Quality, Quality of Life, and Anxiety Levels in People with Type 2 Diabetes Mellitus? Turk. J. Med. Sci. 2021, 51, 735–742.
  79. Pinto, L.C.; Rados, D.V.; Remonti, L.R.; Kramer, C.K.; Leitao, C.B.; Gross, J.L. Efficacy of SGLT2 Inhibitors in Glycemic Control, Weight Loss and Blood Pressure Reduction: A Systematic Review and Meta-Analysis. Diabetol. Metab. Syndr. 2015, 7, A58.
  80. Santulli, G.; Varzideh, F.; Forzano, I.; Wilson, S.; Salemme, L.; De Donato, A.; Lombardi, A.; Rainone, A.; Nunziata, L.; Jankauskas, S.S.; et al. Functional and Clinical Importance of SGLT2-Inhibitors in Frailty: From the Kidney to the Heart. Hypertension 2023, 80, 1800–1809.
  81. Khan, T.; Khan, S.; Akhtar, M.; Ali, J.; Najmi, A.K. Empagliflozin Nanoparticles Attenuates Type2 Diabetes Induced Cognitive Impairment via Oxidative Stress and Inflammatory Pathway in High Fructose Diet Induced Hyperglycemic Mice. Neurochem. Int. 2021, 150, 105158.
  82. Chen, X.; Zhao, J.; Chen, S. Advances in SGLT2 Inhibitor Research on Cognitive Impairment in Type 2 Diabetes. J. Contemp. Med. Pract. 2022, 4, 37.
  83. Wang, S.; Fan, F. Abstract 051: Oral Antihyperglycemic Therapy with a SGLT2 Inhibitor Reverses Cognitive Impairments in Elderly Diabetics. Hypertension 2019, 74, 051.
  84. Pawlos, A.; Broncel, M.; Woźniak, E.; Gorzelak-Pabiś, P. Neuroprotective Effect of SGLT2 Inhibitors. Molecules 2021, 26, 7213.
  85. Mone, P.; Lombardi, A.; Gambardella, J.; Pansini, A.; Macina, G.; Morgante, M.; Frullone, S.; Santulli, G. Empagliflozin Improves Cognitive Impairment in Frail Older Adults with Type 2 Diabetes and Heart Failure With Preserved Ejection Fraction. Diabetes Care 2022, 45, 1247–1251.
  86. Lato, M.; Iberszer, K.; Litwiniuk, M.; Zaniuk, M.; Hurkała, K.; Antonik, D.; Denys, B.; Góra, K.; Zimnicki, P.; Zdziennicki, W. Use of SGLT2 Inhibitors in the Treatment of Cognitive Disorders. J. Educ. Health Sport 2023, 25, 27–39.
  87. Sim, A.Y.; Barua, S.; Kim, J.Y.; Lee, Y.; Lee, J.E. Role of DPP-4 and SGLT2 Inhibitors Connected to Alzheimer Disease in Type 2 Diabetes Mellitus. Front. Neurosci. 2021, 15, 708547.
  88. NCT04304261; Effects of SGLT2i on the Cognitive Function in T2DM Patient (ESCDP). Third Military Medical University: Chongqing, China, 2020. Available online: https://clinicaltrials.gov/show/NCT04304261 (accessed on 30 October 2023).
  89. Tang, H.; Shao, H.; Shaaban, C.E.; Yang, K.; Brown, J.; Anton, S.; Wu, Y.; Bress, A.; Donahoo, W.T.; DeKosky, S.T.; et al. Newer glucose-lowering Drugs and Risk of Dementia: A Systematic Review and meta-analysis of Observational Studies. J. Am. Geriatr. Soc. 2023, 71, 2096–2106.
  90. Panchal, S.; Chhabra, S.; Prasad, B.K.; Aich, B.; Rajani, A. Management of Cognitive Decline in T2DM—SGLT2 Inhibitors at Horizon. Indian J. Endocrinol. Metab. 2018, 22, 20406223221086996.
  91. Cardoso, R.; Graffunder, F.P.; Ternes, C.M.P.; Fernandes, A.; Rocha, A.V.; Fernandes, G.; Bhatt, D.L. SGLT2 Inhibitors Decrease Cardiovascular Death and Heart Failure Hospitalizations in Patients with Heart Failure: A Systematic Review and Meta-Analysis. EClinicalMedicine 2021, 36, 100933.
  92. Llorens-Cebrià, C.; Molina-Van den Bosch, M.; Vergara, A.; Jacobs-Cachá, C.; Soler, M.J. Antioxidant Roles of SGLT2 Inhibitors in the Kidney. Biomolecules 2022, 12, 143.
  93. Tsai, K.-F.; Chen, Y.-L.; Chiou, T.T.-Y.; Chu, T.-H.; Li, L.-C.; Ng, H.-Y.; Lee, W.-C.; Lee, C.-T. Emergence of SGLT2 Inhibitors as Powerful Antioxidants in Human Diseases. Antioxidants 2021, 10, 1166.
  94. Tang, H.; Dai, Q.; Shi, W.; Zhai, S.; Song, Y.; Han, J. SGLT2 Inhibitors and Risk of Cancer in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Diabetologia 2017, 60, 1862–1872.
  95. Chavda, V.; Vashi, R.; Patel, S. Cerebrovascular Complications of Diabetes: SGLT-2 Inhibitors as a Promising Future Therapeutics. Curr. Drug Targets 2021, 22, 1629–1636.
  96. Ren, D.; Sun, Y.; Zhang, D.; Li, D.; Liu, Z.; Jin, X.; Wu, H. SGLT2 Promotes Pancreatic Cancer Progression by Activating the Hippo Signaling Pathway via the HnRNPK-YAP1 Axis. Cancer Lett. 2021, 519, 277–288.
  97. Wu, W.; Zhang, Z.; Jing, D.; Huang, X.; Ren, D.; Shao, Z.; Zhang, Z. SGLT2 Inhibitor Activates the STING/IRF3/IFN-β Pathway and Induces Immune Infiltration in Osteosarcoma. Cell Death Dis. 2022, 13, s11419.
  98. Luo, J.; Hendryx, M.; Dong, Y. Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors and Non-Small Cell Lung Cancer Survival. Br. J. Cancer 2023, 128, 1541–1547.
  99. Shaikh, A.M.Y. SGLT2 Inhibitors and Cancer: Why Further Evidence Is Required. Diabetologia 2017, 60, 2536–2537.
  100. Scafoglio, C.; Hirayama, B.A.; Kepe, V.; Liu, J.; Ghezzi, C.; Satyamurthy, N.; Moatamed, N.A.; Huang, J.; Koepsell, H.; Barrio, J.R.; et al. Functional Expression of Sodium-Glucose Transporters in Cancer. Proc. Natl. Acad. Sci. USA 2015, 112, E4111–E4119.
  101. Wang, Y.; Yang, L.; Mao, L.; Zhang, L.; Zhu, Y.; Xu, Y.; Cheng, Y.; Sun, R.; Zhang, Y.; Ke, J.; et al. SGLT2 Inhibition Restrains Thyroid Cancer Growth via G1/S Phase Transition Arrest and Apoptosis Mediated by DNA Damage Response Signaling Pathways. Cancer Cell Int. 2022, 22, 74.
  102. Xian-Huan, B. Research Progress on Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Tumor. Drugs Clin. 2022, 36, 21756.
  103. Abouelkheir, M.; Taha, A.E. SGLT2 Inhibitors and Cancer: Is Immunity the Missing Link? J. Pharmacol. Clin. Res. 2019, 6, 555699.
  104. Hu, W.-S.; Lin, C.-L. Patients with Diabetes with and without Sodium-Glucose Cotransporter-2 Inhibitors Use with Incident Cancer Risk. J. Diabetes Complicat. 2023, 37, 108468.
  105. Ali, A.; Mekhaeil, B.; Biziotis, O.-D.; Tsakiridis, E.E.; Ahmadi, E.; Wu, J.; Wang, S.; Singh, K.; Menjolian, G.; Farrell, T.; et al. The SGLT2 Inhibitor Canagliflozin Suppresses Growth and Enhances Prostate Cancer Response to Radiotherapy. Commun. Biol. 2023, 6, 919.
  106. Bardaweel, S.; Issa, A. Exploring the Role of Sodium-Glucose Cotransporter as a New Target for Cancer Therapy. J. Pharm. Pharm. Sci. 2022, 25, 253–265.
  107. Hendryx, M.; Dong, Y.; Ndeke, J.M.; Luo, J. Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Initiation and Hepatocellular Carcinoma Prognosis. PLoS ONE 2022, 17, e0274519.
  108. Gyimesi, G.; Pujol-Giménez, J.; Kanai, Y.; Hediger, M.A. Sodium-Coupled Glucose Transport, the SLC5 Family, and Therapeutically Relevant Inhibitors: From Molecular Discovery to Clinical Application. Pflug. Arch. 2020, 472, 1177–1206.
  109. Wu, W.; Wang, Y.; Xie, J.; Fan, S. Empagliflozin: A Potential Anticancer Drug. Discov. Oncol. 2023, 14, 127.
  110. Komatsu, S.; Nomiyama, T.; Numata, T.; Kawanami, T.; Hamaguchi, Y.; Tanaka, T.; Inoue, R.; Yanase, T. SGLT2 Inhibitor Ipragliflozin Induces Breast Cancer Apoptosis via Membrane Hyperpolarization and Mitochondria Dysfunction. Diabetes 2018, 67, 255-OR.
  111. Perry, R.J.; Shulman, G.I. Sodium-Glucose Cotransporter-2 Inhibitors: Understanding the Mechanisms for Therapeutic Promise and Persisting Risks. J. Biol. Chem. 2020, 295, 14379–14390.
  112. Saijo, Y.; Okada, H.; Hata, S.; Nakajima, H.; Kitagawa, N.; Okamura, T.; Osaka, T.; Kitagawa, N.; Majima, S.; Senmaru, T.; et al. Reasons for Discontinuing Treatment with Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Diabetes in Real-World Settings: The KAMOGAWA-A Study. J. Clin. Med. 2023, 12, 6993.
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