Invokana (canagliflozin) / J&J, Daiichi Sankyo, Mitsubishi Tanabe, Mundipharma - LARVOL DELTA

Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors and Risk of Heart Failure Hospitalization in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Cureus) - "This benefit was consistent across most agents, including empagliflozin, canagliflozin, dapagliflozin, and sotagliflozin, while ertugliflozin showed a nonsignificant trend in the same direction. The results demonstrate that SGLT2 inhibitors confer clinically meaningful cardiorenal protection that is recognized to occur through mechanisms largely independent of glucose lowering, reinforcing their role as cornerstone agents in the management of T2DM. These findings highlight the importance of prioritizing SGLT2 inhibitors in contemporary diabetes care to reduce the global burden of heart failure (HF)."

Journal • Retrospective data • Review • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Canagliflozin inhibits NLRP3 Inflammasome activation to protect the Retinal Neurovascular Unit in a Mouse Retinal Vein Occlusion Model. (PubMed, Exp Eye Res) - "Results demonstrated that Canagliflozin reduced RNP formation, inhibited albumin leakage, attenuated glial cells activation, mitigated RGCs loss, and suppressed NLRP3 inflammasome activation in RVO mice, independent of its hypoglycemic and weight-reducing effects. These findings suggested that Canagliflozin protected the retinal NVUs in a mouse RVO model by inhibiting NLRP3 inflammasome activation."

Journal • Preclinical • Retinal Vein Occlusion • NLRP3

Serious adverse events reported with sodium-glucose cotransporter-2 (SGLT2) inhibitors in the FAERS database (2013-2024): a pharmacovigilance study. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Dapagliflozin and empagliflozin accounted for more than 70% SAE reports, followed by canagliflozin (26.63%). SAE reports contributed to a large proportion of reports with SGLT2i in the FAERS database. SAE profile of individual SGLT2i varied."

Adverse events • Journal • Serious adverse event • Dermatology • Inflammation • Metabolic Disorders • Pancreatitis

Canagliflozin as a Potential Preclinical Therapy for Tuberous Sclerosis Complex: Inhibition of Tsc2 -/- Cell Proliferation via Cell Cycle Arrest and Mitochondrial Dysfunction. (PubMed, Drug Des Devel Ther) - "Ca inhibits Tsc2 -/- cell proliferation through dual mechanisms of cell cycle arrest and mitochondrial impairment, demonstrating significant therapeutic potential for TSC-related lesions. These findings highlight Ca as a promising alternative to current mTOR inhibitors, warranting further investigation into its molecular targets and clinical applications."

Journal • Preclinical • Diabetes • Metabolic Disorders • Oncology • Rare Diseases • Type 2 Diabetes Mellitus

The sodium-glucose cotransporter-2 inhibitor canagliflozin alleviates endothelial dysfunction in a rat bypass model. (PubMed, Biochem Pharmacol) - "The reduced immunoreactivity of CD-31 was ameliorated in the IR + CANAinject and IR + CANAsuppl+inject groups. CANA alleviates endothelial dysfunction induced by IR injury in a rodent model of revascularization."

Journal • Preclinical • Cardiovascular • Metabolic Disorders • Reperfusion Injury • Transplantation • CD31 • PECAM1

Clinical pharmacokinetics on canagliflozin: a systematic review of in-vitro and in-vivo studies. (PubMed, Expert Rev Clin Pharmacol) - "Furthermore, co-administration of CFZ with rifampin in humans reduced Cmax by 28%, while with telmisartan in rats, CL/F decreased 31.1% initially, but increased 62.9% after 7 days. This review integrates all significant human PK parameters of CFZ by combining findings from existing studies, allowing researchers to develop and evaluate PK models for recommending model-based dose optimization. : CRD420251054714."

Journal • PK/PD data • Preclinical • Review • Diabetes • Metabolic Disorders • Renal Disease • Type 2 Diabetes Mellitus

Efficacy & safety of sodium-glucose cotransporter-2 inhibitors in polycystic ovary syndrome: A meta-analysis with trial sequential analysis. (PubMed, Indian J Med Res) - "Results Five RCTs with 'low' risk of bias, including 205 patients with PCOS, receiving SGLT2i (empagliflozin, licogliflozin, dapagliflozin, and canagliflozin alone and in combination with metformin) or control (placebo, metformin, or exenatide) were evaluated in the meta-analysis. Interpretation & conclusions The findings of this meta-analysis suggest that SGLT2i improves the hormonal and glycaemic indices in patients with PCOS. It can prove to be a safe alternative in patients not responding to or intolerant of standard pharmacological treatments."

Clinical • Journal • Retrospective data • Acne Vulgaris • Endocrine Disorders • Genetic Disorders • Infertility • Obesity • Polycystic Ovary Syndrome • Sexual Disorders • Women's Health

Pleiotropic Effects of SGLT2 Inhibitors: A Focus on Macrophage-Mediated Action. (PubMed, Pharmacol Res) - "This review summarizes the mechanisms by which dapagliflozin, empagliflozin, and canagliflozin regulate macrophage polarization, metabolic reprogramming, and inflammatory responses. Additionally, their anti-inflammatory effects extend toothers like non-alcoholic fatty liver disease and inflammatory bowel disease. Collectively, SGLT2 inhibitors exhibit multi-organ protective potential through macrophage modulation, positioning them as promising immunomodulatory agents beyond glucose-lowering therapy."

Journal • Review • Atherosclerosis • Cardiovascular • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Renal Disease • Type 2 Diabetes Mellitus • AMPK • IL1B • IL6 • TNFA

Comparison of three types of drugs for cardiovascular and renal benefits in type 2 diabetes mellitus. (PubMed, World J Diabetes) - "T2DM, as one of the most common chronic metabolic diseases, is also one of the most significant risk factors for CVD and CKD. GLP-1RA, SGLT2i, and nsMRAs have emerged as novel therapeutic agents to comprehensively manage T2DM-related CVD and CKD. We conducted a network meta-analysis to compare the efficacy and safety of GLP-1RAs, SGLT2i, and nsMRA in patients with T2DM."

Journal • Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Myocardial Infarction • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Effects of canagliflozin combined with metformin therapy on insulin sensitivity in patients with type 2 diabetes mellitus. (PubMed, Eur J Med Res) - "The combination of canagliflozin and metformin in the treatment of T2DM not only effectively reduces blood glucose levels but also significantly improves insulin sensitivity and pancreatic function, with good safety profiles. For T2DM patients with obesity or insulin resistance, the combination therapy may offer additional benefits in terms of weight management and enhanced insulin sensitivity."

Journal • Diabetes • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Special vascular risk with Canagliflozin. (PubMed, Diabetes Obes Metab) - No abstract available

Journal

Comparison chart: Sodium-glucose cotransporter 2 (SGLT2) inhibitors. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Noninsulin drugs for type 2 diabetes. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

SUPER: SGLT2 Inhibitor Utilization Re-perfusion Therapy (clinicaltrials.gov) - P4 | N=150 | Not yet recruiting | Sponsor: Taichung Veterans General Hospital | Initiation date: Jun 2025 ➔ Dec 2025

Trial initiation date • Cardiovascular • Ischemic stroke • Reperfusion Injury

Glucagon-like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter-2 Inhibitors Reduce Dementia Risk in Type 2 Diabetes: A Comprehensive Bayesian Network Meta-Analysis (AHA 2025) - "For all-cause dementia versus control according to the SUCRA: albiglutide (RR: 0.03, 95% CrI: 0.00 to 0.08; SUCRA: 94.4%), lixisenatide (RR: 0.08, 95% CrI: 0.00 to 0.20; SUCRA: 93.62%), efpeglenatide (RR: 0.24, 95% CrI: 0.00 to 1.38; SUCRA: 70.09%), canagliflozin (RR: 0.31, 95% CrI: 0.01 to 1.47; SUCRA: 61.81%), semaglutide (RR: 0.50, 95% CrI: 0.03 to 1.98; SUCRA: 50.06%), liraglutide (RR: 2.12, 95% CrI: 0.02 to 9.89; SUCRA: 41.91%), empagliflozin (RR: 0.68, 95% CrI: 0.05 to 2.35; SUCRA: 39.63%), exenatide (RR: 4.13, 95% CrI: 0.02 to 20.28; SUCRA: 35.41%), dulaglutide (RR: 3.38, 95% CrI: 0.03 to 15.72; SUCRA: 32.89%), dapagliflozin (RR: 1.19, 95% CrI: 0.09 to 4.96; SUCRA: 30.37%), ertugliflozin (RR: 6.79, 95% CrI: 0.02 to 29.23; SUCRA: 30.1%), control (SUCRA: 19.67%). GLP-1RAs and SGLT2is reduce dementia risk, with albiglutide and lixisenatide excelling for all-cause dementia, dapagliflozin and ertugliflozin for vascular dementia, and dulaglutide for Alzheimer's...."

Retrospective data • Alzheimer's Disease • Cardiovascular • CNS Disorders • Dementia • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

SGLT2 Inhibitors in LVAD Patients: A Multi-Center Propensity-Matched Cohort Analysis (AHA 2025) - "Patients were stratified based on exposure to SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin) post-implant. In this large real-world analysis, SGLT2 inhibitor use in LVAD patients was associated with markedly reduced 1-year mortality and improved cardiorenal and infectious outcomes. These findings suggest a potential role for SGLT2i in optimizing medical therapy in LVAD recipients, a population not included in pivotal HF trials. This retrospective analysis may be affected by residual confounding despite rigorous matching."

Clinical • Acute Kidney Injury • Cardiovascular • Congestive Heart Failure • Heart Failure • Infectious Disease • Nephrology • Renal Disease

Impact of diabetes on the effects of SGLT2 inhibitors on kidney outcomes: An updated drug/dose-dependent meta-analysis. (PubMed, Clin Nephrol) - "SGLT2 inhibitors confer renal protection in both diabetic and non-diabetic populations, supporting their use in CKD management across a broad spectrum of patients. However, careful drug selection is warranted in diabetic patients at risk for DKA."

Journal • Retrospective data • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease

The Relationship between Sodium-Glucose Co-Transporter 2 Inhibitors and Erythrocytosis: A Retrospective Review from a Large Urban Center (ASH 2024) - "The most popular SGLT-2 inhibitor was empagliflozin (79.4%) followed by dapagliflozin (8.8%), ertugliflozin (8.8%), and canagliflozin ( 3%). Given the considerable benefit of SGLT2i, further studies could focus on long-term patient monitoring, as the benefits of continuing SGLT2i may outweigh the risks of discontinuation. Additionally, further education should be provided to primary care providers regarding the possibility of erythrocytosis while on SGLT2i to prevent unnecessary workup, especially if the time to peak Hb/HCT levels is around two years, as our study showed."

Retrospective data • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Hematological Disorders • Metabolic Disorders • Nephrology • Obstructive Sleep Apnea • Renal Disease • Respiratory Diseases • Sleep Disorder • Venous Thromboembolism • JAK2

Association of SGLT2 Inhibitors with Reduced Mortality and Improved Clinical Outcomes in Patients with Cancer and CKD: A Real-World Propensity-Matched Analysis (KIDNEY WEEK 2025) - "Patients prescribed SGLT2i (dapagliflozin, empagliflozin, canagliflozin, ertugliflozin, sotagliflozin) were matched 1:1 to controls without SGLT2i. Conclusion SGLT2i use in cancer patients with CKD is associated with substantial reductions in mortality and major adverse renal, cardiovascular, and healthcare utilization outcomes, but is linked to a higher hazard of DKA. These findings support SGLT2i therapy as a promising strategy in this vulnerable population, with appropriate DKA risk monitoring."

Clinical • Clinical data • Real-world • Real-world evidence • Acute Kidney Injury • Anemia • Chronic Kidney Disease • Congestive Heart Failure • Diabetic Nephropathy • Fatigue • Heart Failure • Metabolic Disorders • Myocardial Infarction • Nephrology • Oncology • Renal Disease

Impact of SGLT2 Inhibitor Use on Cardiac Allograft Vasculopathy and Other Clinical Outcomes in Heart Transplant Recipients: A Propensity-Matched Real-World Study (AHA 2025) - "Exposure was defined as initiation of SGLT2i therapy within 5 years after transplant (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin). In this multicenter real-world cohort of heart transplant recipients, SGLT2 inhibitor use was associated with significantly reduced all-cause mortality, rejection and hospitalization, without an increase in transplant rejection. There was no significant increase in CAV. These findings support the potential role of SGLT2i as a safe adjunct in selected post-transplant patients."

Clinical • Clinical data • Real-world • Real-world evidence • Cardiovascular • Immunology • Transplant Rejection • Transplantation

Computational Analysis of Inhibitor Binding in SGLT2 Variants (KIDNEY WEEK 2025) - "The binding of dapagliflozin and empagliflozin was different to the WT with E99FS, while the binding of dapagliflozin and canagliflozin were different to the wild type in the F98L and Q457H models. SGLT2-MAP17 complex with empagliflozin (green) from PDB 7VSI. Key residues for binding are highlighted in orange."

Cardiovascular • Diabetes • Metabolic Disorders • Nephrology • PDZK1IP1

SGLT2 Inhibitors Rather Than GLP-1 Receptor Agonists Lower the Risk of Kidney Failure: A Systematic Review and Network Meta-Analysis (KIDNEY WEEK 2025) - "Randomized controlled trials (RCTs) comparing SGLT2i or non-exendin-4 GLP-1RA (liraglutide, dulaglutide and semaglutide) vs placebo in adults were considered. No evidence of inconsistency (p = 0.135) or publication bias was detected. Conclusion SGLT2i reduced the risk of kidney failure with empagliflozin, dapagliflozin, and canagliflozin ranking highest, supporting their preferential use in persons at high risk of kidney failure"

Retrospective data • Review • Chronic Kidney Disease • Renal Disease

Efficacy and Safety of Canagliflozin in Patients with Persistent Drop in eGFR Below 30 mL/min per 1.73 m2: Insights from the CREDENCE Clinical Trial (KIDNEY WEEK 2025) - "Figure. Clinical outcomes in patients with persistent GFR decline <30 ml/min/1.73m 2 ."

Clinical • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

SGLT2 Inhibitors and Clinical Outcomes in Kidney Transplant Recipients with Diabetes: A Real-World Cohort Analysis (KIDNEY WEEK 2025) - "Cohort A (n=10,377) included patients on SGLT2 inhibitors (empagliflozin, dapagliflozin, or canagliflozin), while Cohort B (n=95,150) included those not on these agents. Conclusion Among diabetic kidney transplant recipients, SGLT2 inhibitor use was associated with improved graft and patient survival, reduced dialysis dependence, and favorable cardiovascular and infectious outcomes. These findings support the safe use of SGLT2 inhibitors in this population and highlight the need for prospective studies."

Clinical • Clinical data • Real-world • Real-world evidence • Cardiovascular • Diabetes • Diabetic Nephropathy • Infectious Disease • Metabolic Disorders • Myocardial Infarction • Nephrology • Transplantation • Type 2 Diabetes Mellitus

Effect of SGLT2 Inhibitors on Kidney Outcomes in IgAN Following Kidney Transplant: A Real-World Comparative Analysis (KIDNEY WEEK 2025) - "Patients were stratified into two cohorts: Cohort A: Patients who received an SGLT2 inhibitor (empagliflozin, dapagliflozin, or canagliflozin; n=2,068) Cohort B: Patients with no record of SGLT2 use (n=28,005) Primary outcomes included graft failure, dialysis dependence, IgAN recurrence (hematuria), proteinuria, and mortality, assessed using risk ratios and Kaplan–Meier survival analyses. Conclusion In kidney transplant recipients with IgA nephropathy, SGLT2 inhibitor use was associated with a significant reduction in graft failure and dialysis dependence, without an increased risk of hematuria recurrence or proteinuria. These findings support the potential role of SGLT2 inhibitors in improving post-transplant renal outcomes in patients with IgAN, warranting further prospective studies to validate safety and long-term efficacy."

Clinical • Real-world • Real-world evidence • Glomerulonephritis • IgA Nephropathy • Nephrology • Transplantation