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Faizan, Khorajiya* Dr. Khushbu Patel Khushbu Patel Dr. C. N. Patel. "Review Of the Combination Dosage Form of Sitagliptin Phosphate Monohydrate and Dapagliflozin Propanediol Monohydrate as an Anti-Diabetic Agent." International Journal of Pharmaceutical Sciences 3, no. 5 (2025): 2020–27. https://doi.org/10.5281/zenodo.15391282.
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Sitagliptin acting as Anti-Diabetic agent (Dipeptidyl peptidase-4 inhibitor) which boosts post prandial insulin release decreases Glucagon secretion and lower mean time as well as fasting blood glucose in type 2 diabetes mellitus. There is a strong rationale for combining a DPP-4i and a SGLT2i in patients with T2D because the two drugs exert different and complementary glucose-lowering effects. Dual therapy (initial combination or stepwise approach) is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin. This agent is used in combination with other oral hypoglycemic agents. Dapagliflozin acts as Sodium Glucose cotransporter-2(SGLT2) inhibitor. This agent is used in combination with diet and exercise to improve glycemic control in adult with type -2 diabetes mellitus. SGLT2 is major transporter of glucose whose inhibition induces glycosuria and lower blood sugar in type 2 diabetes mellitus. [2] According to the clinical trial Study of World Evidence with SGLT2 and DPP4 in Type2 diabetes mellitus patients in Spain which shows beneficial positive effect on patient of Diabetes Mellitus (Type-2) at the close level of 5-10 mg of Dapagliflozin and 50-100 mg of Sitagliptin. Cardiovascular disease remains the leading cause of mortality in patients with diabetes. Sodium-glucose cotransporter 2 inhibitors and dipeptidyl peptidase-4 inhibitors reported to have positive CV outcomes; especially, combination therapy with dapagliflozin and sitagliptin seem to be suitable therapeutic option. This review discusses introduction, chemistry, pharmacology, pharmacokinetic, rationale and clinical utility of combination therapy with dapagliflozin and sitagliptin in improving glycemic control and reducing cardiovascular events in patients with type 2 diabetes mellitus with multiple cardiovascular risk factors.
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Kim, Mi-kyung, and Jeong Hyun Park. "Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitor." Korean Journal of Medicine 87, no. 1 (2014): 14. http://dx.doi.org/10.3904/kjm.2014.87.1.14.
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Hendryx, Michael, Yi Dong, Jonas M. Ndeke, and Juhua Luo. "Sodium-glucose cotransporter 2 (SGLT2) inhibitor initiation and hepatocellular carcinoma prognosis." PLOS ONE 17, no. 9 (2022): e0274519. http://dx.doi.org/10.1371/journal.pone.0274519.
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Introduction Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs. Emerging findings from laboratory studies indicate that SGLT2 inhibitors can improve liver function and suppress the proliferation of hepatocellular carcinoma (HCC) cells. The aim of this study was to test the hypothesis that initiation of SGLT2 inhibitors improves HCC prognosis in a human population. Methods We used National Surveillance, Epidemiology and End Results (SEER)—Medicare linked data in the United States to evaluate the role of SGLT2 inhibitor initiation on the survival of HCC patients. 3,185 HCC patients newly diagnosed between 2014 and 2017 aged 66 years or older with pre-existing type 2 diabetes were included and followed to the end of 2019. Information on SGLT2 inhibitor initiation was extracted from the Medicare Part D file. Results SGLT2 inhibitor initiation was associated with significantly lower mortality risk after adjusting for potential confounders (HR = 0.68, 95% CI = 0.54–0.86) with stronger association for longer duration of use (HR = 0.60, 95% CI = 0.41–0.88). Further, we found that SGLT2 inhibitor initiation was associated with a lower risk mortality risk ranging from 14% to 60% regardless of patient demographic variables, tumor characteristics, and cancer treatments. Conclusion Our large SEER-Medicare linked data study indicates that SGLT2 inhibitor initiation was associated with improved overall survival of HCC patients with pre-existing type 2 diabetes compared with no SGLT2 inhibitor use. Further studies are needed to confirm our findings and elucidate the possible mechanisms behind the association.
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Kraemer, Anna Lena, and Ian Ramsey. "Sodium-glucose co-transporter 2 inhibitor treatment in diabetic cats." Companion Animal 30, no. 1 (2025): 2–7. https://doi.org/10.12968/coan.2024.0039.
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Sodium-glucose co-transporter 2 inhibitors are oral anti-hyperglycaemic agents that represent a new treatment strategy in feline diabetes mellitus and remove the need for daily injections, dose adjustments and glucose curves. Velagliflozin (Senvelgo; Boehringer Ingelheim) is currently the only licensed sodium-glucose co-transporter 2 inhibitor for use in cats in the UK. It induces glucosuria and thereby lowers blood glucose concentrations, reverses glucotoxicity and improves clinical signs. The most common side effect is loose stools, but these are often self-limiting and short-lived. The most concerning complication of treatment is euglycaemic diabetic ketoacidosis, which is best avoided by appropriate patient selection and effective treatment monitoring.
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Chen, Sha, Qian Wang, Andriana Christodoulou, et al. "Sodium Glucose Cotransporter-2 Inhibitor Empagliflozin Reduces Infarct Size Independently of Sodium Glucose Cotransporter-2." Circulation 147, no. 3 (2023): 276–79. http://dx.doi.org/10.1161/circulationaha.122.061688.
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Mahmood, Nasir, Muhammad Qasim, Talal Safdar, Shazia Yousaf, Muhammad Iqbal Qasim, and Amjad Ali. "Efficacy of Initiating Sodium Glucose Co Transporter 2 Inhibitor (SGLT2I) for Treatment of Type II Diabetes Mellitus." Pakistan Journal of Medical and Health Sciences 16, no. 1 (2022): 951–54. http://dx.doi.org/10.53350/pjmhs22161951.
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Sodium glucose co-transporter 2 (SGLT 2) inhibitors are hypoglycemic agents that have action on kidneys. They cause increased excretion of glucose via kidneys by reducing its absorption. In healthy individuals, kidneys filter almost all of the glucose and return it back into circulation, excreting only a minimum amount in the urine. This reabsorption is facilitated by SGLT 2 receptors which are found in early proximal tubule, with some assistance by sodium glucose co-transporter 1 (SGLT 1). In patients with type 2 diabetes mellitus (T2DM), activity of SGLT 2 is increased. This results in increased absorption of glucose in the bloodcausing further hyperglycemia. Objectives: To determine the efficacy of initiating sodium glucose co transporter2 inhibitor (SGLT2i) in patients with type 2 diabetes mellitus. Study design: Descriptive, case series study Study duration:28th April 2020 to 27th October 2020. Settings: Department of Medicine, Aziz Fatima hospital, Faisalabad and Diabetes & Endocrinology Ward of Hayatabad Medical Complex, Peshawar Materials & Methods: 150 patients with T2D aged between 18 to 60 years. Patients with pregnancy, CHF, those who had received an oral hypoglycemic medication other than metformin for more than 14 days were excluded. All the patients were given Dapagliflozin 10 mg once daily for 26 weeks. For evaluation of HbA1c, blood sampleswere checked and reported by pathologist at hospital. Efficacy was assessed after 26 weeks of treatment. Results:In this study, participants were in the age range from 18 to 60 years with mean age of 40.77 ± 9.42 years. Eighty three patients (55.33%) were between 18 to 40 years of age. Out of 150 patients, 93 (62.0%) were male and 57 (38.0%) were females with male to female ratio 1.6:1. In our study, efficacy of initiating sodium glucose co transporter -2 inhibitor (SGLT2i) in patients of type 2 diabetes mellitus was found in 65 (43.33%) patients. Conclusion: This study concluded that “the efficacy of initiating sodium glucose co transporter - 2 inhibitor (SGLT2i) in patients of type 2 diabetes mellitus is quite high.” Keywords: type 2 diabetes mellitus, sodium glucose co transporter -2 inhibitor,efficacy
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Ashoush, Nermeen. "REVIEW ONPHARMACOKINETICS OF EMPAGLIFLOZIN, AN INHIBITOR OF THE SODIUM GLUCOSE CO-TRANSPORTER-2 (SGLT-2)." Asian Journal of Pharmaceutical and Clinical Research 10, no. 7 (2017): 50. http://dx.doi.org/10.22159/ajpcr.2017.v10i7.18067.
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ABSTRACT Empagliflozin is an inhibitor of the sodium glucose co-transporter-2 (SGLT-2), which is found almost exclusively in the proximal tubules of nephrotic components in the kidneys. SGLT-2 accounts for about 90 percent of glucose reabsorption into the blood. Blocking SGLT-2 reduces blood glucose by blocking glucose reabsorption in the kidney and thereby excreting glucose (i.e., blood sugar) via the urine. Sodium glucose co-transporter-2 (SGLT-2) inhibitors are an optional second-line therapy after metformin; they are generally well tolerated with low risk of hypoglycemia. The various compounds differ with respect to their pharmacokinetic properties; however, their clinical efficacy appears to be similar. The clinical differences between the various compounds stem from effects other than hypoglycemic effects, their safety and side effects profile. The aim of this review was to investigate the different pharmacokinetic studies of empagliflozin in a concise way in the form of tables.
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Koch, Richard A., and Richard F. Clark. "Euglycemic Ketoacidosis With Sodium–Glucose Cotransporter-2 Inhibitor." American Journal of Therapeutics 25, no. 5 (2018): e590-e591. http://dx.doi.org/10.1097/mjt.0000000000000602.
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Mishra, Rahul, Ghada Elshimy, Lakshmi Kannan, and Rishi Raj. "Sodium–glucose cotransporter 2 inhibitor-associated severe epididymo-orchitis." BMJ Case Reports 15, no. 7 (2022): e250942. http://dx.doi.org/10.1136/bcr-2022-250942.
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A man in his late 50s, with uncontrolled type 2 diabetes mellitus (T2DM) and morbid obesity, presented to the hospital with complicated epididymo-orchitis. The onset of symptoms (scrotal pain, erythema and swelling) occurred after the use of empagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, for 2 months. His baseline antidiabetic medications were insulin, glipizide and metformin. Initially, he had failed treatment of epididymo-orchitis with oral levofloxacin for 3 weeks, followed by 2 weeks of doxycycline therapy. At the presentation to the hospital, an ultrasound of the scrotum revealed scrotal and right testicular abscess. The patient underwent right inguinal orchiectomy. Postoperatively, pus culture was positive for Enterococcus faecalis and Candida glabrata, and hence, he was treated with oral antibiotics including high-dose antifungal medications. Adequate wound care and regular follow-up demonstrated resolution of infection. This case highlights the risk of severe urogenital infection associated with the use of SGLT2 inhibitors in the setting of uncontrolled T2DM.
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Bhosale, Shilpushp, Akash Golani, Malini Premkumar Joshi, and Atul Prabhakar Kulkarni. "Perioperative euglycemic DKA: The YIN and YANG of sodium-glucose cotransporter 2 inhibitors." Journal of Anaesthesiology Clinical Pharmacology 41, no. 1 (2025): 193–95. https://doi.org/10.4103/joacp.joacp_59_24.
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Abstract Sodium-glucose cotransporter 2 inhibitors are gaining widespread acceptance in managing diabetic patients due to their favorable cardiac and renal protective effects. However, these drugs can cause a lethal complication described as sodium-glucose cotransporter 2 inhibitor-associated perioperative ketoacidosis (SAPKA) if they are continued until surgery. The FDA recommends stopping these medications at least 4–6 days before surgery to avoid the risk of euglycemic ketoacidosis, which can present a diagnostic challenge for perioperative physicians. We present three patients undergoing colorectal cancer surgeries who on SGLT2 inhibitors developed perioperative SGLT2i-associated perioperative ketoacidosis.
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Atul, Kshirasagar* Ms. Priyanka Zendekar Dr. Gajanan Sanap. "SGLT Inhibitors As Antidiabetic Agents." International Journal in Pharmaceutical Sciences 1, no. 11 (2023): 168–79. https://doi.org/10.5281/zenodo.10084378.
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One of the most prevalent metabolic diseases that significantly raises the burden of disease on the world health system is diabetes mellitus. Diabetes mellitus (DM) is linked to several illnesses and medical disorders, including atherosclerosis, obesity, hypertension, and cardiovascular diseases. Type 1 diabetes, Type 2 diabetes, and gestational diabetes are the three main forms of diabetes mellitus. Many medication classes, including insulin, biguanides, sulfonylureas, metformin, DPP4 inhibitors, GLP-1 inhibitors, and SGLT2 inhibitors, are used to treat or manage diabetes mellitus. Included in this review are the types of diabetes mellitus, medications that treat the condition, and the sodium/glucose co-transporter [SGLT2] inhibitors. Large proteins called sodium/glucose co-transporters (SGLT) enhance the transport of sugars like fructose, galactose, and fructose while also transporting sodium. across a cell's plasma membrane from a range of tissues. The kidney's reabsorption of glucose is enhanced by SGLT receptors. Reduced reabsorption of glucose and increased excretion of glucose through the urine are the results of SGLT2 inhibitor inhibition. FDA-approved medications that are used to manage or control diabetes mellitus include canagliflozin, dapagliflozin, and empagliflozin.
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Hamza Shabbir, Muhammad Rasikh, Khalid Bashir, et al. "Impact of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors on Cardiovascular Events in Type 2 Diabetes." Indus Journal of Bioscience Research 3, no. 1 (2025): 320–24. https://doi.org/10.70749/ijbr.v3i1.496.
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Introduction: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder marked by persistent hyperglycemia and insulin resistance. Objective: The main objective of the study is to find the impact of Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors on cardiovascular events in Type 2 diabetes. Methodology: This randomized control trial was conducted at Shalamar Hospital, Lahore, from 1st March to 31st August 2024. Data were collected from 195 patients. Data were collected at baseline and subsequent follow-up visits through standardized protocols. Results: Data were collected from 195 patients. Only 12.2% of patients in the SGLT2 inhibitor group experienced MACE, compared to 25.8% in the control group, reflecting a 52.7% relative risk reduction (p = 0.01). Similarly, heart failure hospitalizations were reduced to 5.1% in the SGLT2 inhibitor group compared to 15.5% in the control group, yielding a 67% relative risk reduction (p = 0.005). These findings highlight the significant cardiovascular protective effects of SGLT2 inhibitors. The Kaplan-Meier analysis revealed that patients in the SGLT2 inhibitor group had a significantly longer median time to the first cardiovascular event (11.5 months) compared to the control group (8.5 months), with a p-value of 0.002. Conclusion: It is concluded that sodium-glucose cotransporter-2 (SGLT2) inhibitors significantly reduce cardiovascular events in patients with type 2 diabetes mellitus, making them a pivotal advancement in diabetes management.
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Lim, Jia Leng, Georgina Bergero, Yogesh Acharya, James Shaw, and Aaron Liew. "Efficacy and Safety of a Sodium-Glucose Co-Transporter-2 Inhibitor Versus Placebo as an Add-on Therapy for People With Type 2 Diabetes Inadequately Treated With Metformin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Journal of the Endocrine Society 5, Supplement_1 (2021): A469—A470. http://dx.doi.org/10.1210/jendso/bvab048.959.
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Abstract Metformin monotherapy is often insufficient to achieve or sustain glycemic targets in people with type 2 diabetes. Therefore, we performed a systematic review and meta-analysis to assess the efficacy, safety and tolerability of sodium-glucose co-transporter-2 inhibitors versus placebo as add-on therapy after metformin in type 2 diabetes. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search was performed in the PubMed, www.clinicaltrials.gov and Cochrane Central Register of Controlled Trials databases for relevant randomized controlled trials up until 30th October 2020 that compared sodium-glucose co-transporter-2 inhibitors versus placebo as add-on therapy to metformin. A random-effects model was used. Thirteen randomized controlled trials (4270 participants) met the inclusion criteria. Compared with placebo, sodium-glucose co-transporter-2 inhibitor treatment, as add-on therapy to metformin, was associated with a significant reduction in HbA1c level (mean difference [MD]: -0.6%, 95% CI: -0.7, -0.5; p<0.01), fasting plasma glucose level (MD: -1.4mmol/l; 95% CI; -1.5, -1.3; p<0.01), weight (MD: -2.0kg; 95% CI: -2.2, -1.8; p<0.01), systolic blood pressure (MD: -4.7mmHg; 95% Cl: -5.4, -3.9; p<0.01) and diastolic blood pressure (MD: -2.0mmHg; 95% Cl: -2.5, -1.5; p<0.01). Significantly more participants achieved HbA1c <7% (odds ratio [OR]: 3.1; 95% CI: 2.6, 3.6; p<0.01) in the sodium-glucose co-transporter-2 inhibitor group. Genital mycotic infections (OR: 2.6; 95% CI: 1.4, 4.6; p<0.01) were more common with sodium-glucose co-transporter-2 inhibitors, but there was no significant statistical difference in urinary tract infections (OR: 1.4; 95% CI: 1.0, 2.0; p=0.06), in hypoglycemia (OR: 1.5; 95% CI: 1.0, 2.4; p=0.07), or in discontinuation rates due to adverse events (OR: 0.9; 95% CI: 0.6, 1.5; p=0.68) between the two groups. In summary, in comparison with placebo, add-on therapy with a sodium-glucose co-transporter-2 inhibitor is significantly more efficacious in lowering HbA1c, fasting plasma glucose, weight and blood pressure in people with type 2 diabetes following inadequate glycemic control with metformin. The rate of discontinuation due to adverse events was similar despite higher risk of genital mycotic infections.
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Krishnan, Rekha, Rashmi Subramanian, and Raja Selvarajan. "SGLT2 Inhibitor: A Cardio-Renal Metabolic Pill." International Journal of Health Sciences and Research 13, no. 1 (2023): 133–41. http://dx.doi.org/10.52403/ijhsr.20230119.
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Cardiovascular disease and renal disease continue to be the leading causes of morbidity and mortality among people with type 2 diabetes mellitus, despite decades of research into risk-reduction approaches. sodium-glucose transport protein 2 (SGLT2) inhibitors have been approved by the US Food and Drug Administration (FDA) for improving blood sugar control in adult patients with type 2 diabetes mellitus (T2DM Four types of sodium-glucose transport protein 2 (SGLT2) inhibitors (Canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) inhibit SGLT-2 protein expression in renal proximal convoluted tubules, reducing filtration glucose resorption, decreasing Renal Glucose Thresholds (RTG), and increasing urinary glucose excretion. As cardiovascular and renal disease are closely linked to metabolic abnormalities associated with type 2 diabetes mellitus, these conditions can be considered cardiovascular-renal-metabolic disease states. Patients with cardiovascular-renal-metabolic disease states need a holistic approach to managing their disease states. In this article, we discuss the cardiovascular and renal metabolic risks associated with type 2 diabetes mellitus and discuss the mechanism and clinical benefits of SGLT2 inhibitors. Key words: sodium-glucose transport protein 2; glycemic control; Type 2 Diabetes Mellitus; Cardiovascular disease; chronic kidney disease.
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Prattichizzo, Francesco, Lucia La Sala, Lars Rydén, et al. "Glucose-lowering therapies in patients with type 2 diabetes and cardiovascular diseases." European Journal of Preventive Cardiology 26, no. 2_suppl (2019): 73–80. http://dx.doi.org/10.1177/2047487319880040.
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Type 2 diabetes mellitus is a major risk factor for developing cardiovascular disease, and many patients with diabetes have prevalent cardiovascular complications. Recent cardiovascular outcome clinical trials suggest that certain new glucose-lowering drugs are accompanied by additional cardioprotective properties. Indeed, selected glucagon-like peptide-1 receptor agonists have a proved cardiovascular benefit in terms of a reduced incidence of ischaemic events, while sodium/glucose co-transporter-2 inhibitors have also shown significant protection, with a striking effect on heart failure and renal endpoints. These findings have been integrated in recent guidelines which now recommend prescribing (when initial metformin monotherapy fails) a glucagon-like peptide-1 receptor agonist or a sodium/glucose co-transporter-2 inhibitor with clinical trial-confirmed benefit in patients with diabetes and atherosclerotic cardiovascular disease, and a sodium/glucose co-transporter-2 inhibitor in such patients with heart failure or chronic kidney disease at initial stages. Furthermore, the new 2019 European Society of Cardiology guidelines in collaboration with the European Association for the Study of Diabetes recommend a glucagon-like peptide-1 receptor agonist or a sodium/glucose co-transporter-2 inhibitor in treatment-naive patients with type 2 diabetes mellitus with pre-existing cardiovascular disease or at high cardiovascular risk. Future research will disentangle the mechanisms underpinning these beneficial effects and will also establish to what extent these results are generalisable to the whole diabetes population. In the meantime, available evidence should prompt a wide diffusion of these two classes of drugs among patients with diabetes and cardiovascular disease. Here, we briefly summarise recent findings emerging from cardiovascular outcome clinical trials, discuss their impact on treatment algorithms and propose new possible approaches to improve our knowledge further regarding the cardiovascular effect of glucose-lowering medications.
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Klinkner, Gwen, and Maggie Steingraber-Pharr. "Euglycemic Diabetic Ketoacidosis Associated With SGLT2 Inhibitor Therapy: A Case Report." AACN Advanced Critical Care 34, no. 1 (2023): 27–32. http://dx.doi.org/10.4037/aacnacc2023830.
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Sodium-glucose cotransporter-2 inhibitors are now considered second-line treatment agents for type 2 diabetes and offer a unique treatment approach with added cardiorenal benefits. Drugs in this class increase the risk of euglycemic diabetic ketoacidosis, which may be difficult to diagnose if clinicians are not aware of the risk factors and subtle symptoms. This article describes a case of euglycemic diabetic ketoacidosis in a patient with coronary artery disease who was taking a sodium-glucose cotransporter-2 inhibitor and experienced acute mental status changes immediately after heart catheterization.
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Sabirov, I. S., I. T. Murkamilov, and V. V. Fomin. "Potential mechanisms underlying cardiovascular protection by sodium glucose cotransporter 2 inhibitors (empagliflozin)." Complex Issues of Cardiovascular Diseases 10, no. 3 (2021): 79–89. http://dx.doi.org/10.17802/2306-1278-2021-10-3-79-89.
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The presented literature review is devoted to the cardioprotective capabilities of a new class of antihyperglycemic drugs - sodium-glucose cotransporter 2 inhibitors (SGLT2), which improve glycemic control through an insulin-independent mechanism of action associated with an increase in urinary glucose excretion. The article presents the results of large-scale clinical trials on the use of SGLT2 inhibitors in patients with and without diabetes, and with cardiovascular diseases or multiple cardiovascular risk factors. A number of the most frequently discussed cardiac specific mechanisms mediated by the SGLT2 inhibitor affecting the Abstract state of the cardiovascular system are presented. Moreover, the article presents the results of a placebo-controlled clinical trial entitled “Empagliflozin reduces mortality in patients with type 2 diabetes at high cardiovascular risk” (EMPA-REG oUtcOmE) to analyze the cardioprotective capabilities of SGLT2 inhibitor empagliflozin in patients with type 2 diabetes and concomitant cardiovascular diseases. The article emphasizes the importance of further research to determine the degree of contribution of the above-mentioned mechanisms to the cardioprotective potential of SGLT2 inhibitors. PubMed database was used to identify relevant studies and systematic reviews.
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Reddy, N. Surendra, P. Lakshmi, G. Divya, T. S. Durga Prasad, and D. Ranganayakulu. "Dapagliflozin: A new class of drug in the treatment of Type 2 diabetes." Research in Pharmacy and Health Sciences 2, no. 3 (2016): 157–59. http://dx.doi.org/10.32463/rphs.2016.v02i03.31.
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Sodium-glucose co-transporter (SGLT) inhibitors are a new group of oral medications used for treating type 2 diabetes. Dapagliflozin was approved in January 8th, 2014 and is the second selective inhibitor of the sodium-glucose co-transporter 2 (SGLT2) to be marketed in the US. It is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 Diabetes Mellitus (T2DM).It is available 5mg and 10 mg in film coated tablets. It acts by inhibiting SGLT2 decreases plasma glucose by increasing urinary glucose excretion. The common adverse reactions are genital mycotic infection, nasopharyngitis, urinary tract infections, back pain, urination increase, nausea, influenza. It is contraindicated in hypertension, renal impairment, hypoglycemia, genital myotic infections and bladder cancer.
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Glover, Sarah, Matthew E. Borrego, Gretchen M. Ray, and Melissa H. Roberts. "Sodium-Glucose Cotransporter 2 Inhibitor Use Among Individuals Age." ClinicoEconomics and Outcomes Research Volume 14 (July 2022): 465–77. http://dx.doi.org/10.2147/ceor.s361886.
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Kalra, Sanjay, ManashP Baruah, and Rakesh Sahay. "Medication counselling with sodium glucose transporter 2 inhibitor therapy." Indian Journal of Endocrinology and Metabolism 18, no. 5 (2014): 597. http://dx.doi.org/10.4103/2230-8210.139206.
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Heyman, Samuel N., Mogher Khamaisi, Christian Rosenberger, Auryan Szalat, and Zaid Abassi. "Increased Hematocrit During Sodium-Glucose Cotransporter-2 Inhibitor Therapy." Journal of Clinical Medicine Research 9, no. 2 (2017): 176–77. http://dx.doi.org/10.14740/jocmr2849w.
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Petunina, N. A., E. V. Goncharova, M. Е. Теlnova, I. A. Kuzina, N. S. Martirosyan, and A. Yu Sochneva. "Modern inhibitor of sodium-glucose cotransporter type 2 – ertugliflozin." Meditsinskiy sovet = Medical Council, no. 6 (May 12, 2023): 234–40. http://dx.doi.org/10.21518/ms2022-032.
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Diabetes mellitus, a well-known risk of cardiovascular disease (CVD), in patients with type 2 diabetes mellitus (DM2) Hyperglycemia has been found to be an increased risk of coronary heart disease and mortality. In real clinical practice, physicians are faced with the problem of choice when prescribing new hypoglycemic drugs in patients with type 2 diabetes and high cardiovascular risk. Modern possibilities and approaches to the treatment of DM2 have contributed to the creation of a promising class of hypoglycemic drugs that block renal glucose reabsorption - inhibitors of the sodium-glucose cotransporter type 2 (iSGLT-2). The unique mechanism of SGLT2 inhibition not only improves glycemic control, but also has cardio- and nephroprotective effects in patients with DM2 and at high cardiovascular risk. According to current recommendations, when choosing the tactics of treating patients with DM2 and the presence of risk factors for cardiovascular diseases or confirmed atherosclerotic cardiovascular diseases, preference is given to GLP-1 and/or iSGLT-2 receptor agonists in combination with the first-line drug, metformin. This article presents the main results of the efficacy and safety of ertugliflozin in a number of clinical studies and its beneficial effect not only on glycemic control, but also on cardio- and nephroprotective effects. The article also reflects the key results of an extensive program of randomized clinical trials VERTIS (acronym for eValuation of ERTugliflozinefficacy and Safety; evaluation of the efficacy and safety of ertugliflozin): including patients with type 2 diabetes and established atherosclerotic cardiovascular disease (VERTIS CV), with type 2 diabetes and CKD 3rd stage (VERTIS RENAL), as well as VERTIS MONO, VERTIS MET, VERTIS SITA, VERTIS SU and VERTIS FACTORIAL.
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Nickol, J., A. Azmeen, D. Stoller, E. Lyden, R. Zolty, and S. Lundgren. "Sodium Glucose Co-Transporter 2 Inhibitor Use Post-Transplant." Journal of Heart and Lung Transplantation 44, no. 4 (2025): S624. https://doi.org/10.1016/j.healun.2025.02.1341.
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S, S. Singh. "Intractable Metabolic Acidosis Requiring Hemodialysis in a Patient of Lada Treated with Sglt – 2 Inhibitor." International Journal of Medical and Pharmaceutical Research 4, no. 5 (2023): 264–66. https://doi.org/10.5281/zenodo.8419053.
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Sodium Glucose co-transporter – 2 (SGLT-2) inhibitors are class of oral antidiabetic drugs used in the treatment of Type II diabetes Mellitus. They act on the SGLT- 2 protein expressed in the renal proximal convoluted tubules to reduce the absorption of filtered glucose, decrease the renal threshold of glucose and promote glucose excretion. They have gained popularity due to their beneficial effects on heart and kidneys. However their use is associated with increased risk of Euglycemic ketoacidosis. Here we present a case where SGLT – 2 inhibitor used in combination with Insulin in a patient of LADA was associated with D.K.A where severe Metabolic acidosis persisted even after correction of hyperglycemia and dehydration which did not respond to continuous infusion of Dextrose, insulin and Sodium bicarbonate, ultimately requiring Hemodialysis.
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Philippaert, Koenraad, Subha Kalyaanamoorthy, Mohammad Fatehi, et al. "Cardiac Late Sodium Channel Current Is a Molecular Target for the Sodium/Glucose Cotransporter 2 Inhibitor Empagliflozin." Circulation 143, no. 22 (2021): 2188–204. http://dx.doi.org/10.1161/circulationaha.121.053350.
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Background: SGLT2 (sodium/glucose cotransporter 2) inhibitors exert robust cardioprotective effects against heart failure in patients with diabetes, and there is intense interest to identify the underlying molecular mechanisms that afford this protection. Because the induction of the late component of the cardiac sodium channel current (late- I Na ) is involved in the etiology of heart failure, we investigated whether these drugs inhibit late- I Na . Methods: Electrophysiological, in silico molecular docking, molecular, calcium imaging, and whole heart perfusion techniques were used to address this question. Results: The SGLT2 inhibitor empagliflozin reduced late- I Na in cardiomyocytes from mice with heart failure and in cardiac Nav1.5 sodium channels containing the long QT syndrome 3 mutations R1623Q or ΔKPQ. Empagliflozin, dapagliflozin, and canagliflozin are all potent and selective inhibitors of H 2 O 2 -induced late- I Na (half maximal inhibitory concentration = 0.79, 0.58, and 1.26 µM, respectively) with little effect on peak sodium current. In mouse cardiomyocytes, empagliflozin reduced the incidence of spontaneous calcium transients induced by the late- I Na activator veratridine in a similar manner to tetrodotoxin, ranolazine, and lidocaine. The putative binding sites for empagliflozin within Nav1.5 were investigated by simulations of empagliflozin docking to a three-dimensional homology model of human Nav1.5 and point mutagenic approaches. Our results indicate that empagliflozin binds to Nav1.5 in the same region as local anesthetics and ranolazine. In an acute model of myocardial injury, perfusion of isolated mouse hearts with empagliflozin or tetrodotoxin prevented activation of the cardiac NLRP3 (nuclear-binding domain-like receptor 3) inflammasome and improved functional recovery after ischemia. Conclusions: Our results provide evidence that late- I Na may be an important molecular target in the heart for the SGLT2 inhibitors, contributing to their unexpected cardioprotective effects.
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Dobbins, Robert L., Frank L. Greenway, Lihong Chen, et al. "Selective sodium-dependent glucose transporter 1 inhibitors block glucose absorption and impair glucose-dependent insulinotropic peptide release." American Journal of Physiology-Gastrointestinal and Liver Physiology 308, no. 11 (2015): G946—G954. http://dx.doi.org/10.1152/ajpgi.00286.2014.
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GSK-1614235 and KGA-2727 are potent, selective inhibitors of the SGLT1 sodium-dependent glucose transporter. Nonclinical (KGA-2727) and clinical (GSK-1614235) trials assessed translation of SGLT1 inhibitor effects from rats to normal human physiology. In rats, KGA-2727 (0.1 mg/kg) or vehicle was given before oral administration of 3- O-methyl-α-d-glucopyranose (3- O-methylglucose, 3-OMG) containing 3-[3H]OMG tracer. Tracer absorption and distribution were assessed from plasma, urine, and fecal samples. SGLT1 inhibition reduced urine 3-OMG recovery and increased fecal excretion. SGLT1 inhibitor effects on plasma glucose, insulin, gastric inhibitory peptide (GIP), and glucagon-like peptide-1 (GLP-1) concentrations were also measured during a standard meal. Incremental glucose, insulin, and GIP concentrations were decreased, indicating downregulation of β-cell and K cell secretion. Minimal effects were observed in the secretion of the L cell product, GLP-1. With the use of a three-way, crossover design, 12 healthy human subjects received placebo or 20 mg GSK-1614235 immediately before or after a meal. Five minutes into the meal, 3-OMG was ingested. Postmeal dosing had little impact, yet premeal dosing delayed and reduced 3-OMG absorption, with an AUC0–10 of 231 ± 31 vs. 446 ± 31 μg·h−1·ml−1, for placebo. Recovery of tracer in urine was 1.2 ± 0.7 g for premeal dosing and 2.2 ± 0.1 g for placebo. Incremental concentrations of insulin, C-peptide, and GIP were reduced for 2 h with premeal GSK-1614235. Total GLP-1 concentrations were significantly increased, and a trend for increased peptide YY (PYY) was noted. SGLT1 inhibitors block intestinal glucose absorption and reduce GIP secretion in rats and humans, suggesting SGLT1 glucose transport is critical for GIP release. Conversely, GLP-1 and PYY secretion are enhanced by SGLT1 inhibition in humans.
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Song, Su Hyun, and Eun Hui Bae. "Sodium-Glucose Cotransporter 2 Inhibitors for Chronic Kidney Disease: A Comprehensive Review." Korean Journal of Medicine 99, no. 2 (2024): 61–68. http://dx.doi.org/10.3904/kjm.2024.99.2.61.
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Chronic Kidney Disease (CKD) is a major global health burden. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated potential in slowing CKD progression. We evaluated the expanding role of SGLT2 inhibitors, emphasizing their renoprotective benefits in diabetic and non-diabetic CKD patients. We also investigated the underlying mechanisms, including the reduction of glomerular hypertension via modulation of tubuloglomerular feedback. Our study critically analyzed current indications for SGLT2 inhibitor therapy based on recent clinical trial data. To optimize patient outcomes, we present a comprehensive analysis of practical considerations for the prescription of SGLT2 inhibitors, including the potential initial decline in the estimated glomerular filtration rate and a review of adverse events.
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Choi, Min-Koo, So Jeong Nam, Hye-Young Ji, Mi Jie Park, Ji-Soo Choi, and Im-Sook Song. "Comparative Pharmacokinetics and Pharmacodynamics of a Novel Sodium-Glucose Cotransporter 2 Inhibitor, DWP16001, with Dapagliflozin and Ipragliflozin." Pharmaceutics 12, no. 3 (2020): 268. http://dx.doi.org/10.3390/pharmaceutics12030268.
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Since sodium-glucose cotransporter 2 (SGLT2) inhibitors reduced blood glucose level by inhibiting renal tubular glucose reabsorption mediated by SGLT2, we aimed to investigate the pharmacokinetics and kidney distribution of DWP16001, a novel SGLT2 inhibitor, and to compare these properties with those of dapagliflozin and ipragliflozin, representative SGLT2 inhibitors. The plasma exposure of DWP16001 was comparable with that of ipragliflozin but higher than that of dapagliflozin. DWP16001 showed the highest kidney distribution among three SGLT2 inhibitors when expressed as an area under curve (AUC) ratio of kidney to plasma (85.0 ± 16.1 for DWP16001, 64.6 ± 31.8 for dapagliflozin and 38.4 ± 5.3 for ipragliflozin). The organic anion transporter-mediated kidney uptake of DWP16001 could be partly attributed to the highest kidney uptake. Additionally, DWP16001 had the lowest half-maximal inhibitory concentration (IC50) to SGLT2, a target transporter (0.8 ± 0.3 nM for DWP16001, 1.6 ± 0.3 nM for dapagliflozin, and 8.9 ± 1.7 nM for ipragliflozin). The inhibition mode of DWP16001 on SGLT2 was reversible and competitive, but the recovery of the SGLT2 inhibition after the removal of SGLT2 inhibitors in CHO cells overexpressing SGLT2 was retained with DWP16001, which is not the case with dapagliflozin and ipragliflozin. In conclusion, selective and competitive SGLT2 inhibition of DWP16001 could potentiate the efficacy of DWP16001 in coordination with the higher kidney distribution and retained SGLT2 inhibition of DWP16001 relative to dapagliflozin and ipragliflozin.
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Bardhi, Olgert, Matthew D. Bloom, and Maryam Sattari. "Euglycaemic diabetic ketoacidosis in a patient with pancreatitis and type 2 diabetes on empagliflozin." BMJ Case Reports 15, no. 6 (2022): e247921. http://dx.doi.org/10.1136/bcr-2021-247921.
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Sodium glucose cotransporter-2 (SGLT2) inhibitors are glucose-lowering drugs with proven efficacy in treating type 2 diabetes mellitus, and more recently, have been shown to improve heart failure outcomes in patients without diabetes. A rare complication of SGLT2 inhibitor use is the development of euglycaemic diabetic ketoacidosis (EDKA), characterised by euglycaemia (blood glucose level <250 mg/dL), metabolic acidosis (arterial pH <7.3 and serum bicarbonate <18 mEq/L), and ketonaemia. Given patients with EDKA do not present with the typical manifestations of diabetic ketoacidosis, including marked hyperglycaemia and dehydration, the diagnosis of EDKA may be missed and initiation of treatment delayed. We present the case of a man with recent SGLT2 inhibitor use and multiple other risk factors who developed EDKA.
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Baek, Jong Ha, Tae Jung Oh, Ju-Young Moon, et al. "The Effect of Long-term Sodium-glucose Cotransporter 2 Inhibitor Treatment on Renal Function in the Patients with Type 2 Diabetes." Korean Journal of Medicine 95, no. 4 (2020): 236–43. http://dx.doi.org/10.3904/kjm.2020.95.4.236.
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Chronic kidney disease is developed commonly in type 2 diabetes mellitus (T2DM) and is the most common cause of end-stage renal disease and related cardiovascular complications. Meanwhile, despite the current standard of care including optimized glucose control and the use of single-agent blockade of the renin-angiotensin-aldosterone system (RAAS), patients with T2DM remain at increased risk for death and complications from cardiorenal causes. The recent studies using sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown not only glucose lowering effect, but also a reduction in blood pressure, weight loss, and a lowering cardiovascular risk. Regarding renal outcomes, the use of SGLT2 inhibitor slows the progression of kidney disease compared to placebo when added to standard care. However, concern has been raised that currently available SGLT2 inhibitors in Korea may be also associated with improved renal outcomes with long-term treatment. As a result, we aimed to evaluate the effect of long-term SGLT2 inhibitor treatment on renal function in the patients with T2DM using meta-analysis. (Korean J Med 2020;95:236-243)
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Siao, Wun-Zhih, Tsung-Kun Lin, Jing-Yang Huang, Chin-Feng Tsai, and Gwo-Ping Jong. "The association between sodium-glucose cotransporter 2 inhibitors and incident dementia: A nationwide population-based longitudinal cohort study." Diabetes and Vascular Disease Research 19, no. 3 (2022): 147916412210981. http://dx.doi.org/10.1177/14791641221098168.
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Background The association of the use of sodium-glucose cotransporter 2 (SGLT2) inhibitor and incident dementia remains unclear. This study aimed to evaluate the risk of incident dementia with the use of SGLT2 inhibitor. Methods This is a population-based cohort study utilizing Taiwan’s National Health Insurance Research Database. Each patient who took SGLT2 inhibitors was assigned to the SGLT2 inhibitor group, whereas 1:1 propensity score-matched randomly selected patients who were nonusers of SGLT2 inhibitors were assigned to the non-SGLT2 inhibitor group. The study outcome was incident dementia. Results A total of 976,972 patients newly diagnosed with type 2 diabetes mellitus (DM) between 2011 and 2018 were included in this study. After the patients’ propensity score matching by age, sex, duration of DM, comorbidities and drug index date of the patients, a total of 103,247 patients in the SGLT2 inhibitor group and 103,247 in the non-SGLT2 inhibitor group were enrolled for analysis. The SGLT2 inhibitor group was associated with a lower risk of incident dementia (adjusted hazard ratio: 0.89, 95% confidence interval: 0.82–0.96; p = .0021). Diabetic complications were significantly lower in the SGLT2 inhibitor group compared with the non-SGLT2 group. Sensitivity analysis was also consistent with the main analysis. Conclusions Patients with type 2 DM who were prescribed SGLT2 inhibitors were associated with a lower risk of incident dementia compared with those not prescribed SGLT2 inhibitors in real-world practice.
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Rozado, José, Daniel García Iglesias, Miguel Soroa, et al. "Sodium-Glucose Cotransporter-2 Inhibitors at Discharge from Cardiology Hospitalization Department: Decoding A New Clinical Scenario." Journal of Clinical Medicine 9, no. 8 (2020): 2600. http://dx.doi.org/10.3390/jcm9082600.
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Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) are new glucose-lowering drugs (GLDs) with demonstrated cardiovascular benefits in patients with heart disease and type-2 diabetes mellitus (T2DM). However, their safety and efficacy when prescribed at hospital discharge are unexplored. This prospective, observational, longitudinal cohort study included 104 consecutive T2DM patients discharged from the cardiology department between April 2018 and February 2019. Patients were classified based on SGLT-2 inhibitor prescription and adjusted by propensity-score matching. The safety outcomes included discontinuation of GLDs; worsening renal function; and renal, hepatic, or metabolic hospitalization. The efficacy outcomes were death from any cause, cardiovascular death, cardiovascular readmission, and combined clinical outcome (cardiovascular death or readmission). The results showed that, the incidence rates of safety outcomes were similar in the SGLT-2 inhibitor or non-SGLT-2 inhibitor groups. Regarding efficacy, the SGLT-2 inhibitors group resulted in a lower rate of combined clinical outcomes (18% vs. 42%; hazard ratio (HR), 0.35; p = 0.02), any cause death (0% vs. 24%; HR, 0.79; p = 0.001) and cardiovascular death (0% vs. 17%; HR, 0.83; p = 0.005). No significant differences were found in cardiovascular readmissions. SGLT-2 inhibitor prescription at hospital discharge in patients with heart disease and T2DM was safe, well tolerated, and associated with a reduction in all-cause and cardiovascular deaths.
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Putra, Muhammad Gilang Dwi. "Sodium Glucose Co-Transporter-2 (SGLT 2) Inhibitor as A Therapy For Heart Failure With Low Ejection Fraction (HFrEF)." FITOFARMAKA: Jurnal Ilmiah Farmasi 12, no. 2 (2022): 148–55. http://dx.doi.org/10.33751/jf.v12i2.5767.
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Heart failure is a major cause of cardiovascular morbidity and mortality worldwide despite advances in prevention and management. Recent clinical trial findings have shown that sodium-glucose co-transporter 2 inhibitor (SGLT2i) produces effects other than lowering blood glucose levels, i.e., exhibits beneficial cardiovascular effects. The purpose of this paper is to determine the role of SGLT2i in heart failure patients with low ejection fraction (HFrEF) so that it can be used as a guide for future management. This study is a narrative review by searching on Google Scholar through several keywords. The period including articles obtained is articles from 2014 to 2022. The diuretic effect of SGLT2i can cause an increase in cardiac preload. The reduction in cardiac afterload likely occurs through a decrease in blood pressure and arterial stiffness resulting in increased endocardial blood flow. SGLT2i has a beneficial effect on the heart remodeling process. SGLT2i can prevent heart failure by increasing the production of ATP from the oxidation of ketone bodiesSGLT2i in heart failure patients can reduce blood pressure, maintain a decrease in eGFR and reduce the risk of acute kidney injury (AKI) in patients. SGLT2i is very effective in the treatment of HFrEF patients. Because of these advantages, further research is needed in Indonesia in order to determine the effectiveness and impact of giving SGLT2i to HFrEF patients in Indonesia.
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Kim, Won Jin, and Sang Soo Kim. "The Side Effects of Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor." Journal of Korean Diabetes 15, no. 3 (2014): 158. http://dx.doi.org/10.4093/jkd.2014.15.3.158.
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Baruah, ManashPratim, BM Makkar, VikrantB Ghatnatti, and Kaushik Mandal. "Sodium glucose co-transporter-2 inhibitor: Benefits beyond glycemic control." Indian Journal of Endocrinology and Metabolism 23, no. 1 (2019): 140. http://dx.doi.org/10.4103/ijem.ijem_160_17.
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Baig, Muhammad Akbar, and Joshua Nogar. "Euglycemia despite a sodium glucose co-transporter 2 inhibitor overdose." World Journal of Emergency Medicine 13, no. 2 (2022): 147. http://dx.doi.org/10.5847/wjem.j.1920-8642.2022.050.
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Bogdanffy, Matthew S., Robert F. Stachlewitz, Susan van Tongeren, et al. "Nonclinical Safety of the Sodium-Glucose Cotransporter 2 Inhibitor Empagliflozin." International Journal of Toxicology 33, no. 6 (2014): 436–49. http://dx.doi.org/10.1177/1091581814551648.
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Empagliflozin, a selective inhibitor of the renal tubular sodium-glucose cotransporter 2, was developed for treatment of type 2 diabetes mellitus. Nonclinical safety of empagliflozin was studied in a battery of tests to support global market authorization. Safety pharmacology studies indicated no effect of empagliflozin on measures of respiratory or central nervous system function in rats or cardiovascular safety in telemeterized dogs. In CD-1 mouse, Wistar Han rat, or beagle dogs up to 13, 26, or 52 weeks of treatment, respectively, empagliflozin exhibited a toxicity profile consistent with secondary supratherapeutic pharmacology related to glucose loss and included decreased body weight and body fat, increased food consumption, diarrhea, dehydration, decreased serum glucose and increases in other serum parameters reflective of increased protein catabolism, gluconeogenesis, and electrolyte imbalances, and urinary changes such as polyuria and glucosuria. Microscopic changes were consistently observed in kidney and included tubular nephropathy and interstitial nephritis (dog), renal mineralization (rat) and tubular epithelial cell karyomegaly, single cell necrosis, cystic hyperplasia, and hypertrophy (mouse). Empagliflozin was not genotoxic. Empagliflozin was not carcinogenic in female mice or female rats. Renal adenoma and carcinoma were induced in male mice only at exposures 45 times the maximum clinical dose. These tumors were associated with a spectrum of nonneoplastic changes suggestive of a nongenotoxic, cytotoxic, and cellular proliferation-driven mechanism. In male rats, testicular interstitial cell tumors and hemangiomas of the mesenteric lymph node were observed; both tumors are common in rats and are unlikely to be relevant to humans. These studies demonstrate the nonclinical safety of empagliflozin.
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Alipour, Meysam, Jalal Rezaei, Venus Shahabi Rabori, et al. "Limb amputation following sodium-glucose cotransporter type 2 inhibitor therapy." Journal of Preventive Epidemiology 10, no. 1 (2024): e38251. https://doi.org/10.34172/jpe.2025.38251.
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This review article examines the association between sodium-glucose cotransporter type 2 inhibitors (SGLT2i) and the risk of limb amputation, particularly in patients with type 2 diabetes mellitus. This review aims to provide a comprehensive understanding of the risks associated with SGLT2i therapy and to inform future research directions in this area. While SGLT2i medications, such as canagliflozin, are recognized for their cardiovascular and renal benefits, emerging evidence suggests a potential increase in the risk of lower limb amputations (LLAs) among users compared to non-users of SGLT2i. This review synthesizes findings from various studies that report a slightly elevated risk of amputation linked to SGLT2i therapy, with mechanisms proposed including diuretic-induced hypovolemia and the partial inhibition of sodium-glucose cotransporter 1. Factors such as pre-existing peripheral artery disease (PAD), sensory neuropathy, and poor foot health are identified as significant risk enhancers for lower limb amputations in this patient population. In conclusion, patients with these conditions are at increased risk of limb ischemia and subsequent amputation, and the administration of SGLT2 inhibitors may potentially further increase this risk.
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Nassif, Michael E., and James L. Januzzi. "Implementing Sodium-Glucose Cotransporter-2 Inhibitor Therapy for Heart Failure." Journal of the American College of Cardiology 80, no. 19 (2022): 1785–87. http://dx.doi.org/10.1016/j.jacc.2022.09.008.
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Ramakrishnan, Pavithra, Neetika Garg, Samantha Pabich, Didier A. Mandelbrot, and Kurtis J. Swanson. "Sodium-glucose cotransporter-2 inhibitor use in kidney transplant recipients." World Journal of Transplantation 13, no. 5 (2023): 239–49. http://dx.doi.org/10.5500/wjt.v13.i5.239.
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Type 1 diabetes mellitus (T1DM) is one of the important causes of chronic kidney disease (CKD) and end-stage renal failure (ESRF). Even with the best available treatment options, management of T1DM poses significant challenges for clinicians across the world, especially when associated with CKD and ESRF. Substantial increases in morbidity and mortality along with marked rise in treatment costs and marked reduction of quality of life are the usual consequences of onset of CKD and progression to ESRF in patients with T1DM. Simultaneous pancreas-kidney transplant (SPK) is an attractive and promising treatment option for patients with advanced CKD/ESRF and T1DM for potential cure of these diseases and possibly several complications. However, limited availability of the organs for transplantation, the need for long-term immunosuppression to prevent rejection, peri- and post-operative complications of SPK, lack of resources and the expertise for the procedure in many centers, and the cost implications related to the surgery and postoperative care of these patients are major issues faced by clinicians across the globe. This clinical update review compiles the latest evidence and current recommendations of SPK for patients with T1DM and advanced CKD/ESRF to enable clinicians to care for these diseases.
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Balkanski, Stefan. "Dapagliflozin – structure, synthesis, and new indications." Pharmacia 68, no. (3) (2021): 591–96. https://doi.org/10.3897/pharmacia.68.e70626.
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Dapagliflozin is a sodium-glucose co-transporter-2 (SGLT2) inhibitors used in the treatment of patients with type 2 diabetes. An aryl glycoside with significant effect as glucose-lowering agents, Dapagliflozin also has indication for patients with Heart Failure and Chronic Kidney Disease. This review examines the structure, synthesis, analysis, structure activity relationship and uses of the product. The studies behind this drug have opened the doors for the new line of treatment – a drug that reduces blood glucoses, decreases the rate of heart failures, and has a positive effect on patients with chronic kidney disease.
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Chonko, Kayla, Giavanna Russo-Alvarez, Diana Isaacs, Lu Wang, and Amanda Soric. "Prevalence of Sodium Glucose Cotransporter 2 (SGLT-2) Inhibitor Prescribing in Patients with Type 2 Diabetes Mellitus and Reduced Estimated Glomerular Filtration Rate." INNOVATIONS in pharmacy 14, no. 2 (2023): 9. http://dx.doi.org/10.24926/iip.v14i2.5456.
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Sodium glucose cotransporter 2 (SGLT-2) inhibitors have demonstrated benefit in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), including slowing the progression of CKD and lowering the risk of kidney failure and death. Despite this evidence, literature suggests SGLT-2 inhibitors are underutilized in this population. To assess prescribing practices and identify potential variables predictive of SGLT-2 inhibitor prescribing, a non-interventional, retrospective, cross-sectional study was conducted in patients with T2DM and reduced estimated glomerular filtration rate (eGFR). The primary outcome compared prevalence of SGLT-2 inhibitor prescribing in patients with T2DM and eGFR of 30-44 mL/min/1.73m2 to patients with T2DM and eGFR 45-59 mL/min/1.73m2. The secondary outcome described possible predictors of prescribing SGLT-2 inhibitors in this population. Of the 9,387 patients identified with T2DM and reduced eGFR, an SGLT-2 inhibitor was prescribed to 324 (12.2%) patients with eGFR of 30-44 mL/min/1.73m2 versus 799 (11.9%) patients with eGFR of 45-59 mL/min/1.73m2. Patients more likely to be prescribed SGLT-2 inhibitors were younger, male, had a higher body mass index (BMI), a higher hemoglobin A1c (HbA1c), were on other antihyperglycemic medications, had concomitant cardiovascular disease, or had concomitant heart failure. This study found no significant difference in prevalence of SGLT-2 inhibitor prescribing between patients with T2DM and eGFR 30-44 mL/min/1.73m2 versus eGFR 45-59 mL/min/1.73m2 (p=0.70). Further exploration into the causes of low SGLT-2 inhibitor prescribing prevalence is warranted given the growing evidence supporting the use of these agents in patients with T2DM and reduced renal function.
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Hsieh, Cheng-Yang, and Sheng-Feng Sung. "From Kidney Protection to Stroke Prevention: The Potential Role of Sodium Glucose Cotransporter-2 Inhibitors." International Journal of Molecular Sciences 24, no. 1 (2022): 351. http://dx.doi.org/10.3390/ijms24010351.
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Chronic kidney disease (CKD) is an independent risk factor for stroke and covert cerebrovascular disease, and up to 40% of stroke patients have concomitant CKD. However, the so-called “cerebrorenal interaction” attracted less attention compared to its cardiorenal counterpart. Diabetes is the leading cause of CKD. The sodium–glucose cotransporter (SGLT) 2 inhibitor is a relatively new class of oral anti-diabetic drugs and has cardiorenal benefits in addition to glucose-lowering effects. In the present perspective, we would like to review the current status and future potential of the SGLT2 inhibitor in cerebro–renal interactions and strokes regardless of the status of diabetes. We propose the potential roles of baseline renal functions and SGLT1/2 dual inhibition in stroke prevention, as well as the additional benefits of reducing atrial fibrillation and hemorrhagic stroke for SGLT2 inhibitors. Further clinical trials are anticipated to test whether SGLT2 inhibitors can fulfill the long-standing unmet clinical need and stop such a vicious cycle of cerebro–renal interaction.
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Sipos, Ádám, Eszter Szennyes, Nikolett Éva Hajnal, et al. "Dual-Target Compounds against Type 2 Diabetes Mellitus: Proof of Concept for Sodium Dependent Glucose Transporter (SGLT) and Glycogen Phosphorylase (GP) Inhibitors." Pharmaceuticals 14, no. 4 (2021): 364. http://dx.doi.org/10.3390/ph14040364.
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A current trend in the quest for new therapies for complex, multifactorial diseases, such as diabetes mellitus (DM), is to find dual or even multi-target inhibitors. In DM, the sodium dependent glucose cotransporter 2 (SGLT2) in the kidneys and the glycogen phosphorylase (GP) in the liver are validated targets. Several (β-D-glucopyranosylaryl)methyl (het)arene type compounds, called gliflozins, are marketed drugs that target SGLT2. For GP, low nanomolar glucose analogue inhibitors exist. The purpose of this study was to identify dual acting compounds which inhibit both SGLTs and GP. To this end, we have extended the structure-activity relationships of SGLT2 and GP inhibitors to scarcely known (C-β-D-glucopyranosylhetaryl)methyl arene type compounds and studied several (C-β-D-glucopyranosylhetaryl)arene type GP inhibitors against SGLT. New compounds, such as 5-arylmethyl-3-(β-D-glucopyranosyl)-1,2,4-oxadiazoles, 5-arylmethyl-2-(β-D-glucopyranosyl)-1,3,4-oxadiazoles, 4-arylmethyl-2-(β-D-glucopyranosyl)pyrimidines and 4(5)-benzyl-2-(β-D-glucopyranosyl)imidazole were prepared by adapting our previous synthetic methods. None of the studied compounds exhibited cytotoxicity and all of them were assayed for their SGLT1 and 2 inhibitory potentials in a SGLT-overexpressing TSA201 cell system. GP inhibition was also determined by known methods. Several newly synthesized (C-β-D-glucopyranosylhetaryl)methyl arene derivatives had low micromolar SGLT2 inhibitory activity; however, none of these compounds inhibited GP. On the other hand, several (C-β-D-glucopyranosylhetaryl)arene type GP inhibitor compounds with low micromolar efficacy against SGLT2 were identified. The best dual inhibitor, 2-(β-D-glucopyranosyl)-4(5)-(2-naphthyl)-imidazole, had a Ki of 31 nM for GP and IC50 of 3.5 μM for SGLT2. This first example of an SGLT-GP dual inhibitor can prospectively be developed into even more efficient dual-target compounds with potential applications in future antidiabetic therapy.
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Shi, Fang-Hong, Hao Li, Long Shen, et al. "Beneficial Effect of Sodium-Glucose Co-transporter 2 Inhibitors on Left Ventricular Function." Journal of Clinical Endocrinology & Metabolism 107, no. 4 (2021): 1191–203. http://dx.doi.org/10.1210/clinem/dgab834.
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Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowered the risk of cardiovascular events in patients with diabetes or heart failure (HF) with reduced ejection fraction, whether they directly promote cardiac function remains unclear. Therefore, we sought to determine whether SGLT2 inhibitors could improve left ventricular (LV) function in these patients. Methods A literature search was conducted using MEDLINE, EMBASE, and Cochrane Library databases from their inception to July 9, 2021. Randomized clinical trials and cohort studies that reported LV function-related variables were included. Results Thirteen studies comprising 1437 patients (830 SGLT2 inhibitor-treated and 607 non-SGLT2 inhibitor-treated patients) and representing 7 randomized controlled trials with 640 individuals and 6 cohort studies with 797 individuals were included in this meta-analysis. LV regression [LV mass (LVM)], LV ejection fractions (LVEF), LV volumes [LV end-diastolic volumes and systolic volumes (LVEDV and LVESV, respectively], and LV diastolic function [mitral inflow E velocity to tissue Doppler e’ ratio, E/e’ and left atrial volume index (LAVI)] were all significantly improved in patients treated with SGLT2 inhibitors (weighted mean differences, 95% CI, LVM: −6.319 g, −10.850 to −1.789; LVEF: 2.458%, 0.693 to 4.224; LVEDV: −9.134 mL, −15.808 to −2.460; LVESV: −8.440 mL, −15.093 to −1.787; LAVI: −2.791 mL/m2, −.554 to −1.027; E/e’: −1.567, −2.440 to −0.698). Subgroup analysis further confirmed the improvement of LV function mainly in patients with HF or those receiving empagliflozin treatment. Conclusions Treatment with SGLT2 inhibitors can significantly improve LV function in patients with or without diabetes (especially those with HF or undergoing empagliflozin treatment).
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Kambara, Takahiro, Rei Shibata, Hiroyuki Osanai, et al. "Importance of sodium-glucose cotransporter 2 inhibitor use in diabetic patients with acute heart failure." Therapeutic Advances in Cardiovascular Disease 13 (January 2019): 175394471989450. http://dx.doi.org/10.1177/1753944719894509.
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Background: It is known that once heart failure occurs in older patients with diabetes, the overall prognosis is extremely poor. We investigated whether early initiation of SGLT2 inhibitor therapy after admission was beneficial for diabetic patients requiring inpatient treatment for acute heart failure. Methods: We retrospectively assessed consecutive patients with comorbid diabetes who were admitted to the Department of Cardiology in Tosei General Hospital for treatment of acute heart failure. Patients were divided into two groups: those who initiated SGLT2 inhibitor therapy (SGLT2 inhibitor group; mean age: 73 ± 9 years) and those who did not receive the inhibitors during hospitalization (conventional treatment group; mean age: 75 ± 10 years). Results: No intergroup differences were observed in the distribution of either the severity or classes of heart failure on admission. Glycosylated hemoglobin levels were significantly higher in the SGLT2 inhibitor group (HbA1c: 8.1% ± 0.8%) than in the conventional treatment group (HbA1c: 7.1% ± 0.8%) ( p = 0.003). After admission, patients in both groups recovered equally well, and in almost the same period of time, before discharge. The rate of diuretics use at the time of discharge in the SGLT2 inhibitor group ( n = 8, 67%) was significantly lower than that in the conventional treatment group ( n = 19, 100%) ( p = 0.016). In particular, the dose of loop diuretics in the conventional treatment group was 34 ± 4 mg/day while that in the SGLT2 inhibitor group was significantly lower at 13 ± 5 mg/day ( p = 0.008). During hospitalization, the incidence of acute kidney injury was significantly higher in the conventional treatment group ( n = 11, 58%) than in the SGLT2 inhibitor group ( n = 2, 16%) ( p = 0.031). Conclusions: For the treatment and management of heart failure in patients with diabetes, early initiation of SGLT2 inhibitor therapy appears to be effective.
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Perry, Rachel J., and Gerald I. Shulman. "Sodium-glucose cotransporter-2 inhibitors: Understanding the mechanisms for therapeutic promise and persisting risks." Journal of Biological Chemistry 295, no. 42 (2020): 14379–90. http://dx.doi.org/10.1074/jbc.rev120.008387.
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In a healthy person, the kidney filters nearly 200 g of glucose per day, almost all of which is reabsorbed. The primary transporter responsible for renal glucose reabsorption is sodium-glucose cotransporter-2 (SGLT2). Based on the impact of SGLT2 to prevent renal glucose wasting, SGLT2 inhibitors have been developed to treat diabetes and are the newest class of glucose-lowering agents approved in the United States. By inhibiting glucose reabsorption in the proximal tubule, these agents promote glycosuria, thereby reducing blood glucose concentrations and often resulting in modest weight loss. Recent work in humans and rodents has demonstrated that the clinical utility of these agents may not be limited to diabetes management: SGLT2 inhibitors have also shown therapeutic promise in improving outcomes in heart failure, atrial fibrillation, and, in preclinical studies, certain cancers. Unfortunately, these benefits are not without risk: SGLT2 inhibitors predispose to euglycemic ketoacidosis in those with type 2 diabetes and, largely for this reason, are not approved to treat type 1 diabetes. The mechanism for each of the beneficial and harmful effects of SGLT2 inhibitors—with the exception of their effect to lower plasma glucose concentrations—is an area of active investigation. In this review, we discuss the mechanisms by which these drugs cause euglycemic ketoacidosis and hyperglucagonemia and stimulate hepatic gluconeogenesis as well as their beneficial effects in cardiovascular disease and cancer. In so doing, we aim to highlight the crucial role for selecting patients for SGLT2 inhibitor therapy and highlight several crucial questions that remain unanswered.
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Blaschek, Wolfgang. "Natural Products as Lead Compounds for Sodium Glucose Cotransporter (SGLT) Inhibitors." Planta Medica 83, no. 12/13 (2017): 985–93. http://dx.doi.org/10.1055/s-0043-106050.
Full textAbstract:
AbstractGlucose homeostasis is maintained by antagonistic hormones such as insulin and glucagon as well as by regulation of glucose absorption, gluconeogenesis, biosynthesis and mobilization of glycogen, glucose consumption in all tissues and glomerular filtration, and reabsorption of glucose in the kidneys. Glucose enters or leaves cells mainly with the help of two membrane integrated transporters belonging either to the family of facilitative glucose transporters (GLUTs) or to the family of sodium glucose cotransporters (SGLTs). The intestinal glucose absorption by endothelial cells is managed by SGLT1, the transfer from them to the blood by GLUT2. In the kidney SGLT2 and SGLT1 are responsible for reabsorption of filtered glucose from the primary urine, and GLUT2 and GLUT1 enable the transport of glucose from epithelial cells back into the blood stream.The flavonoid phlorizin was isolated from the bark of apple trees and shown to cause glucosuria. Phlorizin is an inhibitor of SGLT1 and SGLT2. With phlorizin as lead compound, specific inhibitors of SGLT2 were developed in the last decade and some of them have been approved for treatment mainly of type 2 diabetes. Inhibition of SGLT2 eliminates excess glucose via the urine. In recent times, the dual SGLT1/SGLT2 inhibitory activity of phlorizin has served as a model for the development and testing of new drugs exhibiting both activities.Besides phlorizin, also some other flavonoids and especially flavonoid enriched plant extracts have been investigated for their potency to reduce postprandial blood glucose levels which can be helpful in the prevention and supplementary treatment especially of type 2 diabetes.
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Ritchie, Duncan Taylor, and James Dixon. "SGLT-2 inhibitor associated euglycaemic diabetic ketoacidosis in an orthopaedic trauma patient." BMJ Case Reports 15, no. 9 (2022): e250233. http://dx.doi.org/10.1136/bcr-2022-250233.
Full textAbstract:
Euglycaemic diabetic ketoacidosis is a serious but rare adverse effect of treatment with sodium-glucose cotransporter-2 (SGLT-2) inhibitors. A man in his 60s with type 2 diabetes mellitus underwent total hip replacement for an intracapsular neck of femur fracture. His SGLT-2 inhibitor was continued perioperatively and blood glucose levels were normal throughout the admission. A diagnosis of severe euglycaemic diabetic ketoacidosis was made in the operating theatre which required treatment in a critical care unit. This resulted in increased morbidity due to decreased postoperative mobilisation and a new requirement for subcutaneous insulin. This case highlights the need for withholding SGLT-2 inhibitors in patients admitted for emergency surgery and a need for regular ketone monitoring in these patients, even in the context of normoglycaemia.
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Shrestha, Abhigan Babu, Anupam Halder, Kripa Rajak, et al. "Cardioprotective effects of sodium glucose cotransporter 2 inhibitor versus dipeptidyl peptidase 4 inhibitor in type 2 diabetes: A meta-analysis of comparative safety and efficacy." SAGE Open Medicine 12 (January 2024). http://dx.doi.org/10.1177/20503121241261204.
Full textAbstract:
Background: Sodium glucose cotransporter 2 inhibitors are recommended for the treatment of heart failure due to their cardioprotective effects, despite primarily being used as antidiabetic medications. However, the comparative profile of two antidiabetic drugs, sodium glucose cotransporter 2 inhibitors with dipeptidyl peptidase 4 inhibitor remains unclear. Study hypothesis: This study aims to compare the safety and efficacy profiles of sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase 4 inhibitor drugs. Methods: A comprehensive search was conducted in PubMed, Scopus, Web of Science, Google Scholar, and ClinicalTrials.gov using appropriate Medical Subject Headings terms from inception until February 23, 2023. The outcomes were pooled using a random-effects model for hazard ratio with a 95% confidence interval. A p-value of <0.05 was considered statistically significant. Results: Twelve studies were included after systematic screening, with a sample size of 745,688 for sodium glucose cotransporter 2 inhibitors and 769,386 for dipeptidyl peptidase 4 inhibitor. The mean age in each group was 61.1 (8.52) and 61.28 (9.25) years, respectively. Upon pooling the included articles with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase 4 inhibitor, the primary outcome of all-cause death demonstrated an hazard ratio of 0.64 (0.57, 0.70), I2: 65.54%, p < 0.001, and major adverse cardiovascular events yielded an hazard ratio of 0.76 (0.65, 0.86), I2: 87.83%, p < 0.001. The secondary outcomes included myocardial infarction with an hazard ratio of 0.84 (0.78, 0.90), I2: 47.64%, p < 0.001, stroke with an hazard ratio of 0.81 (0.75, 0.87), I2: 36.78%, p < 0.001, and hospitalization with an hazard ratio of 0.62 (0.53, 0.70), I2: 83.32%, p < 0.001. Conclusion: Our findings suggest that compared to dipeptidyl peptidase 4 inhibitor, initiating treatment with sodium glucose cotransporter 2 inhibitors provides cardiovascular disease protection and may be considered in patients with type 2 diabetes.