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1.
Zhonghua Yi Xue Za Zhi ; 104(22): 2059-2065, 2024 Jun 11.
Article in Chinese | MEDLINE | ID: mdl-38858216

ABSTRACT

Objective: To investigate the effect of Dapagliflozin, sodium-glucose cotransporter 2 inhibitor (SGLT2i), on contrast-induced acute kidney injury (CIAKI) in patients with type 2 diabetes mellitus (T2DM) after percutaneous coronary intervention(PCI). Methods: A cohort study. The clinical data of 366 patients with coronary heart disease combined with T2DM who underwent PCI in the Department of Cardiology, Tianjin University Chest Hospital, from June 2021 to June 2022 were retrospectively analyzed, including 218 males and 148 females, aged (64.6±11.0) years old. According to whether the patients had used Dapagliflozin or not, the selected patients were divided into SGLT2i group(n=124) and control group(n=242). The changes in cardiac indicators, renal function, and inflammatory response indicators before and 72 hours after PCI treatment were analyzed and compared between the two groups. The incidence rate of CIAKI in the two groups was analyzed, and the influencing factors of CIAKI were analyzed by multivariate logistic regression. The major adverse cardiac events (MACE) were recorded during the follow-up period of the two groups, and Kaplan-Meier survival analysis and log-rank test were used to compare the differences in MACE occurrence between the two group. Results: The left ventricular ejection fraction (LVEF) of the SGLT2i group was lower than that of the control group, and the proportion of patients with LVEF<45% and CIAKI risk score were higher than those of the control group, with statistical significance (all P<0.05). 72 h after PCI treatment, ß-2 Microglobulin(ß-2MG), cystatin-C(Cys-C), and neutrophil gelatinase-associated lipocalin (NGAL) in both groups were all increased compared to those before PCI treatment, with statistical significance (all P<0.05).ß-2MG, Cys-C, and NGAL in SGLT2i group were all lower than those in the control group, with statistical significance(all P<0.05).The levels of interleukin-6(IL-6), hypersensitive C-reactive protein (hs-CRP), and malondialdehyde in both groups of patients increased compared to preoperative levels, while the levels of superoxide dismutase (SOD) decreased compared to preoperative levels, with statistical significance (all P<0.05). The levels of IL-6, hs-CRP, and malondialdehyde in the SGLT2i group were lower than those in the control group, while SOD was higher than that in the control group, with statistical significance (all P<0.05). Among all patients included, 34 cases experienced CIAKI (9.8%), and the incidence of CIAKI in the SGLT2i group was lower than that in the control group [4.8% (6/124) vs 11.6% (28/242),P=0.037]. Multivariate logistic regression analysis showed that the use of dapagliflozin was a protective factor for CIAKI in T2DM patients receiving PCI treatment (OR=0.321, 95%CI: 0.127-0.816, P=0.017). After a follow-up of 14.0 (12.0, 16.2) months, the incidence of MACE in SGLT2i group was lower than that in the control group (7.3% vs 12.8%, P=0.048). Conclusions: Dapagliflozin may reduce the risk of CIAKI and MACE in T2DM patients after PCI treatment. Its mechanism may be related to the anti-inflammatory and antioxidant effects of SGLT2i.


Subject(s)
Acute Kidney Injury , Benzhydryl Compounds , Diabetes Mellitus, Type 2 , Glucosides , Percutaneous Coronary Intervention , Sodium-Glucose Transporter 2 Inhibitors , Humans , Male , Female , Percutaneous Coronary Intervention/adverse effects , Glucosides/therapeutic use , Benzhydryl Compounds/therapeutic use , Benzhydryl Compounds/adverse effects , Middle Aged , Retrospective Studies , Aged , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Contrast Media/adverse effects , Coronary Artery Disease , Cohort Studies
2.
J Natl Compr Canc Netw ; 22(2D)2024 Jun.
Article in English | MEDLINE | ID: mdl-38862004

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for development of hepatocellular carcinoma (HCC). The association between risk of developing HCC and treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP4i) is currently unknown. This study aimed to compare the risk of new-onset HCC in patients treated with SGLT2i versus DPP4i. METHODS: This was a retrospective cohort study of patients with T2DM in Hong Kong receiving either SGLT2i or DPP4i between January 1, 2015, and December 31, 2020. Patients with concurrent DPP4i and SGLT2i use were excluded. Propensity score matching (1:1 ratio) was performed by using the nearest neighbor search. Multivariable Cox regression was applied to identify significant predictors. RESULTS: A total of 62,699 patients were included (SGLT2i, n=22,154; DPP4i, n=40,545). After matching (n=44,308), 166 patients (0.37%) developed HCC: 36 in the SGLT2i group and 130 in the DPP4i group over 240,269 person-years. Overall, SGLT2i use was associated with lower risks of HCC (hazard ratio [HR], 0.42; 95% CI, 0.28-0.79) compared with DPP4i after adjustments. The association between SGLT2i and HCC development remained significant in patients with cirrhosis or advanced fibrosis (HR, 0.12; 95% CI, 0.04-0.41), hepatitis B virus (HBV) infection (HR, 0.32; 95% CI, 0.17-0.59), or hepatitis C virus (HCV) infection (HR, 0.41; 95% CI, 0.22-0.80). The results were consistent in different risk models, propensity score approaches, and sensitivity analyses. CONCLUSIONS: SGLT2i use was associated with a lower risk of HCC compared with DPP4i use after adjustments, and in the context of cirrhosis, advanced fibrosis, HBV infection, and HCV infection.


Subject(s)
Carcinoma, Hepatocellular , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Liver Neoplasms , Sodium-Glucose Transporter 2 Inhibitors , Humans , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/virology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Male , Female , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Retrospective Studies , Middle Aged , Aged , Risk Factors
3.
Cardiovasc Diabetol ; 23(1): 197, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849829

ABSTRACT

OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis. RESEARCH AND DESIGN METHODS: This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type 2 diabetes (T2D) without known heart failure. Subjects were randomized to 12 months of daily 10 mg dapagliflozin or placebo. For all patients, blood/plasma samples and cardiac magnetic resonance imaging (CMRI) were obtained at time of randomization and at the end of 12 months. Systemic inflammation was assessed by plasma IL-1B, TNFα, IL-6 and ketone levels and PBMC mitochondrial respiration, an emerging marker of sterile inflammation. Global myocardial strain was assessed by feature tracking; cardiac fibrosis was assessed by T1 mapping to calculate extracellular volume fraction (ECV); and cardiac tissue inflammation was assessed by T2 mapping. RESULTS: Between the baseline and 12-month time point, plasma IL-1B was reduced (- 1.8 pg/mL, P = 0.003) while ketones were increased (0.26 mM, P = 0.0001) in patients randomized to dapagliflozin. PBMC maximal oxygen consumption rate (OCR) decreased over the 12-month period in the placebo group but did not change in patients receiving dapagliflozin (- 158.9 pmole/min/106 cells, P = 0.0497 vs. - 5.2 pmole/min/106 cells, P = 0.41), a finding consistent with an anti-inflammatory effect of SGLT2i. Global myocardial strain, ECV and T2 relaxation time did not change in both study groups. GOV REGISTRATION: NCT03782259.


Subject(s)
Benzhydryl Compounds , Biomarkers , Diabetes Mellitus, Type 2 , Glucosides , Inflammation Mediators , Sodium-Glucose Transporter 2 Inhibitors , Humans , Benzhydryl Compounds/therapeutic use , Benzhydryl Compounds/adverse effects , Glucosides/therapeutic use , Glucosides/adverse effects , Female , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Male , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Middle Aged , Aged , Treatment Outcome , Inflammation Mediators/blood , Biomarkers/blood , Time Factors , Anti-Inflammatory Agents/therapeutic use , Fibrosis , Inflammation/drug therapy , Inflammation/blood , Inflammation/diagnosis , Double-Blind Method , Myocardium/pathology , Myocardium/metabolism , Diabetic Cardiomyopathies/etiology , Diabetic Cardiomyopathies/prevention & control , Diabetic Cardiomyopathies/diagnostic imaging , Diabetic Cardiomyopathies/drug therapy , Diabetic Cardiomyopathies/blood
4.
BMC Cardiovasc Disord ; 24(1): 285, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816795

ABSTRACT

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are recommended for treatment of heart failure (HF), regardless of type 2 diabetes (T2DM) status. However, limited data exist on SGLT2i prescribing in HF patients without T2DM or across HF subtypes. METHODS: This was a serial, cross-sectional study of US MarketScan commercial and Medicare claims (2013-2021). Prevalence of SGLT2i was calculated by calendar year among HFrEF and HFpEF patients and stratified by T2DM status. RESULTS: Among 218,066 HFrEF patients [mean (SD): 54.9 (8.92) years; 66.4% male], the prevalence of SGLT2i use increased from 0.3 to 18.6%, while among 150,437 HFpEF patients [56.5 (7.77) years; 47.6% male], it rose from 0.5 to 9.9%. These increases were driven by the subgroup with comorbid T2DM. SGLT2i prevalence use ratios among patients with T2DM compared to those without decreased from > 100 in 2018 to 3.8 in 2021 among HFrEF patients, and from 83.1 in 2018 to 17.5 in 2021, coinciding with the publication of landmark trials and corresponding changes in clinical guidelines. CONCLUSIONS: SGLT2i use rose rapidly following changes in guidelines but remained low among those without T2DM. By the end of the study, approximately 1 in 3 HFrEF and 1 in 5 HFpEF patients with T2DM were using an SGLT2i, compared to only 1 in 11 HFrEF and 1 in 85 HFpEF patients without T2DM. Future work identifying barriers with the uptake of GDMT, including SGLT2i, among HF patients is needed.


Subject(s)
Diabetes Mellitus, Type 2 , Heart Failure , Practice Patterns, Physicians' , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Male , Heart Failure/drug therapy , Heart Failure/diagnosis , Heart Failure/physiopathology , Heart Failure/epidemiology , Female , Cross-Sectional Studies , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Aged , Practice Patterns, Physicians'/trends , United States/epidemiology , Middle Aged , Time Factors , Drug Prescriptions , Databases, Factual , Stroke Volume/drug effects , Medicare , Comorbidity , Guideline Adherence/trends
5.
Diabetes Obes Metab ; 26(7): 2905-2914, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38719436

ABSTRACT

AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear. MATERIALS AND METHODS: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease). RESULTS: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (ß = -0.609, p = .039; ß = -2.298, p < .001; ß = -0.936, p = .048; ß = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001). CONCLUSIONS: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes.


Subject(s)
Databases, Factual , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Disease Progression , Glomerular Filtration Rate , Renal Insufficiency, Chronic , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Glomerular Filtration Rate/drug effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/physiopathology , Male , Female , Japan/epidemiology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/complications , Middle Aged , Aged , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/physiopathology , Kidney/drug effects , Kidney/physiopathology
6.
Pharmacoepidemiol Drug Saf ; 33(5): e5800, 2024 May.
Article in English | MEDLINE | ID: mdl-38719731

ABSTRACT

PURPOSE: This study was undertaken to evaluate the potential risk of acute pancreatitis with empagliflozin in patients with type 2 diabetes (T2D) newly initiating empagliflozin. METHODS: Data from two large US claims databases were analyzed in an observational study of patients with T2D receiving metformin who were newly prescribed empagliflozin versus sulfonylurea (SU). Because dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have been associated with the risk of acute pancreatitis in some studies, patients on these agents were excluded. Using pooled analyses of data from the two databases (2014-2021), patients initiating empagliflozin were matched 1:1 within database to patients initiating SU using propensity scores (PS) that incorporated relevant demographic and clinical characteristics. Prespecified sensitivity analyses were performed for design parameters. RESULTS: The analyses identified 72 661 new users of empagliflozin and 422 018 new users of SUs, with both patient groups on concurrent metformin therapy. Baseline characteristics within treatment groups appeared to be similar across the 72 621 matched pairs. After mean follow-up of ~6 months, incidence rates of acute pancreatitis in the pooled matched cohort were 10.30 (95% confidence interval [CI] 9.29-11.39) events per 1000 patient-years (PY) for empagliflozin and 11.65 (95% CI 10.59-12.77) events per 1000 PY for SUs. On a background of metformin, patients newly initiating empagliflozin did not have an increased risk of acute pancreatitis compared with those initiating an SU (pooled PS matched hazard ratio 0.88 [0.76-1.02]) across 75621.42 PY of follow-up. CONCLUSIONS: The results of this voluntary post-approval safety study provide additional evidence that the use of empagliflozin for the treatment of T2D is not associated with an increased risk of acute pancreatitis.


Subject(s)
Benzhydryl Compounds , Diabetes Mellitus, Type 2 , Glucosides , Metformin , Pancreatitis , Sulfonylurea Compounds , Humans , Benzhydryl Compounds/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Pancreatitis/chemically induced , Pancreatitis/epidemiology , Glucosides/adverse effects , Glucosides/therapeutic use , Glucosides/administration & dosage , Sulfonylurea Compounds/adverse effects , Sulfonylurea Compounds/therapeutic use , Male , Female , Middle Aged , Aged , Metformin/adverse effects , Metformin/administration & dosage , Metformin/therapeutic use , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/administration & dosage , Databases, Factual , Incidence , Product Surveillance, Postmarketing/statistics & numerical data , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Adult , United States/epidemiology , Propensity Score
7.
Pak J Pharm Sci ; 37(2): 357-366, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38767103

ABSTRACT

Insulin resistance complicates diabetes care. Its effectiveness and tolerability as an addition to metformin, DPP4 inhibitor and insulin treatment in type 2 diabetic patients will be examined in this research. Participants with type 2 diabetes from poor socio-economic backgrounds had HbA1c values ≥8.5% when using Insulin+Metformin+DPP-4 inhibitors. They received 10mg Empagliflozin daily for 12 weeks (n=143). The main outcome was change in HbA1c at 12th week from baseline. Secondary outcomes were baseline weight and week 12 FPG. Adjusted mean (SE) HbA1c increases at week 12 were: Mean ± SD 10.38 (6.8-17.0) vs. Mean±SD 9.05±1.77 (5.60-16.0) with empagliflozin 10mg. When added to the regimen, empagliflozin significantly reduced FPG, systolic and diastolic blood pressure. The mean (SE) BMI increases from baseline were 31.28±5.89 (16.0-66.0) and 29.73±5.47 (3.0-46.0) with 10mg empagliflozin. Two individuals experienced urinary tract infections as AEs, but no genital infections. Adding empagliflozin 10mg daily to metformin+DPP4 inhibitor+insulin improved glycemic control, body weight and blood pressure for 12 weeks. The intervention was well-tolerated, highlighting empagliflozin's therapeutic potential.


Subject(s)
Benzhydryl Compounds , Diabetes Mellitus, Type 2 , Drug Therapy, Combination , Glucosides , Hypoglycemic Agents , Insulin , Metformin , Obesity , Humans , Glucosides/adverse effects , Glucosides/administration & dosage , Glucosides/therapeutic use , Benzhydryl Compounds/adverse effects , Benzhydryl Compounds/therapeutic use , Benzhydryl Compounds/administration & dosage , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/administration & dosage , Middle Aged , Male , Female , Metformin/administration & dosage , Metformin/therapeutic use , Metformin/adverse effects , Obesity/drug therapy , Glycated Hemoglobin/metabolism , Treatment Outcome , Blood Glucose/drug effects , Blood Glucose/metabolism , Adult , Aged , Administration, Oral , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/administration & dosage , Sodium-Glucose Transporter 2 Inhibitors/administration & dosage , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects
8.
Cochrane Database Syst Rev ; 5: CD015588, 2024 05 21.
Article in English | MEDLINE | ID: mdl-38770818

ABSTRACT

BACKGROUND: Diabetes is associated with high risks of premature chronic kidney disease (CKD), cardiovascular diseases, cardiovascular death and impaired quality of life. People with diabetes are more likely to develop kidney impairment, and approximately one in three adults with diabetes have CKD. People with CKD and diabetes experience a substantially higher risk of cardiovascular outcomes. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors have shown potential effects in preventing kidney and cardiovascular outcomes in people with CKD and diabetes. However, new trials are emerging rapidly, and evidence synthesis is essential to summarising cumulative evidence. OBJECTIVES: This review aimed to assess the benefits and harms of SGLT2 inhibitors for people with CKD and diabetes. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 17 November 2023 using a search strategy designed by an Information Specialist. Studies in the Register are continually identified through regular searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled studies were eligible if they evaluated SGLT2 inhibitors versus placebo, standard care or other glucose-lowering agents in people with CKD and diabetes. CKD includes all stages (from 1 to 5), including dialysis patients. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the study risk of bias. Treatment estimates were summarised using random effects meta-analysis and expressed as a risk ratio (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The primary review outcomes were all-cause death, 3-point and 4-point major adverse cardiovascular events (MACE), fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, and kidney failure. MAIN RESULTS: Fifty-three studies randomising 65,241 people with CKD and diabetes were included. SGLT2 inhibitors with or without other background treatments were compared to placebo, standard care, sulfonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitors, or insulin. In the majority of domains, the risks of bias in the included studies were low or unclear. No studies evaluated the treatment in children or in people treated with dialysis. No studies compared SGLT2 inhibitors with glucagon-like peptide-1 receptor agonists or tirzepatide. Compared to placebo, SGLT2 inhibitors decreased the risk of all-cause death (20 studies, 44,397 participants: RR 0.85, 95% CI 0.78 to 0.94; I2 = 0%; high certainty) and cardiovascular death (16 studies, 43,792 participants: RR 0.83, 95% CI 0.74 to 0.93; I2 = 29%; high certainty). Compared to placebo, SGLT2 inhibitors probably make little or no difference to the risk of fatal or nonfatal MI (2 studies, 13,726 participants: RR 0.95, 95% CI 0.80 to 1.14; I2 = 24%; moderate certainty), and fatal or nonfatal stroke (2 studies, 13,726 participants: RR 1.07, 95% CI 0.88 to 1.30; I2 = 0%; moderate certainty). Compared to placebo, SGLT2 inhibitors probably decrease 3-point MACE (7 studies, 38,320 participants: RR 0.89, 95% CI 0.81 to 0.98; I2 = 46%; moderate certainty), and 4-point MACE (4 studies, 23,539 participants: RR 0.82, 95% CI 0.70 to 0.96; I2 = 77%; moderate certainty), and decrease hospital admission due to heart failure (6 studies, 28,339 participants: RR 0.70, 95% CI 0.62 to 0.79; I2 = 17%; high certainty). Compared to placebo, SGLT2 inhibitors may decrease creatinine clearance (1 study, 132 participants: MD -2.63 mL/min, 95% CI -5.19 to -0.07; low certainty) and probably decrease the doubling of serum creatinine (2 studies, 12,647 participants: RR 0.70, 95% CI 0.56 to 0.89; I2 = 53%; moderate certainty). SGLT2 inhibitors decrease the risk of kidney failure (6 studies, 11,232 participants: RR 0.70, 95% CI 0.62 to 0.79; I2 = 0%; high certainty), and kidney composite outcomes (generally reported as kidney failure, kidney death with or without ≥ 40% decrease in estimated glomerular filtration rate (eGFR)) (7 studies, 36,380 participants: RR 0.68, 95% CI 0.59 to 0.78; I2 = 25%; high certainty) compared to placebo. Compared to placebo, SGLT2 inhibitors incur less hypoglycaemia (16 studies, 28,322 participants: RR 0.93, 95% CI 0.89 to 0.98; I2 = 0%; high certainty), and hypoglycaemia requiring third-party assistance (14 studies, 26,478 participants: RR 0.75, 95% CI 0.65 to 0.88; I2 = 0%; high certainty), and probably decrease the withdrawal from treatment due to adverse events (15 studies, 16,622 participants: RR 0.94, 95% CI 0.82 to 1.08; I2 = 16%; moderate certainty). The effects of SGLT2 inhibitors on eGFR, amputation and fracture were uncertain. No studies evaluated the effects of treatment on fatigue, life participation, or lactic acidosis. The effects of SGLT2 inhibitors compared to standard care alone, sulfonylurea, DPP-4 inhibitors, or insulin were uncertain. AUTHORS' CONCLUSIONS: SGLT2 inhibitors alone or added to standard care decrease all-cause death, cardiovascular death, and kidney failure and probably decrease major cardiovascular events while incurring less hypoglycaemia compared to placebo in people with CKD and diabetes.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Randomized Controlled Trials as Topic , Renal Insufficiency, Chronic , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Renal Insufficiency, Chronic/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Cardiovascular Diseases/prevention & control , Bias , Cause of Death , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Benzhydryl Compounds/therapeutic use , Benzhydryl Compounds/adverse effects , Glucosides/therapeutic use , Glucosides/adverse effects
9.
Pharmacotherapy ; 44(6): 444-466, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38773917

ABSTRACT

Sodium glucose co-transporter 2 (SGLT2) inhibitors are used for the treatment of diabetes and for their cardiovascular and kidney benefits in patients with or without diabetes. Use in solid organ transplant recipients is controversial because transplant recipients were excluded from the major clinical trials assessing SGLT2 inhibitors. The goal of this review was to assess the available literature regarding the use of SGLT2 inhibitors in solid organ transplant recipients. A PubMed search was conducted for studies published in English through December 31, 2023. Studies were excluded if they were meta-analyses, review articles, commentaries, single case reports, or in vitro studies, or did not involve the use of SGLT2 inhibitors in solid organ transplant recipients with a diabetic, cardiovascular, or kidney outcome being assessed. In the final review, 20 studies were included: kidney (n = 15), heart (n = 4), and liver/lung/kidney (n = 1) transplant recipients. SGLT2 inhibitors had similar A1c reduction efficacy and were found to be weight neutral with possible weight reduction effects. Cardiovascular and kidney outcomes were not adequately assessed in the available studies. Adverse effects were reported to occur at a similar rate in transplant recipients compared to the general population. SGLT2 inhibitors were initiated ≥1-year post-transplant in most transplant recipients included in these studies. The overall safety and antihyperglycemic efficacy of SGLT2 inhibitors in kidney and heart transplant recipients is similar to the general population. Data assessing SGLT2 inhibitors use in solid organ transplant recipients for longer durations are needed.


Subject(s)
Organ Transplantation , Sodium-Glucose Transporter 2 Inhibitors , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Humans , Transplant Recipients , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/administration & dosage , Diabetes Mellitus, Type 2/drug therapy
10.
Cardiovasc Diabetol ; 23(1): 184, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811998

ABSTRACT

BACKGROUND: Use of sodium-glucose-cotransporter-2 (SGLT2) inhibitors often causes an initial decline in glomerular filtration rate (GFR). This study addresses the question whether the initial decline of renal function with SGLT2 inhibitor treatment is related to vascular changes in the systemic circulation. METHODS: We measured GFR (mGFR) and estimated GFR (eGFR) in 65 patients with type 2 diabetes (T2D) at baseline and after 12 weeks of treatment randomized either to a combination of empagliflozin and linagliptin (SGLT2 inhibitor based treatment group) (n = 34) or metformin and insulin (non-SGLT2 inhibitor based treatment group) (n = 31). mGFR was measured using the gold standard clearance technique by constant infusion of inulin. In addition to blood pressure (BP), we measured pulse wave velocity (PWV) under standardized conditions reflecting vascular compliance of large arteries, as PWV is considered to be one of the most reliable vascular parameter of cardiovascular (CV) prognosis. RESULTS: Both mGFR and eGFR decreased significantly after initiating treatment, but no correlation was found between change in mGFR and change in eGFR in either treatment group (SGLT2 inhibitor based treatment group: r=-0.148, p = 0.404; non-SGLT2 inhibitor based treatment group: r = 0.138, p = 0.460). Noticeably, change in mGFR correlated with change in PWV (r = 0.476, p = 0.005) in the SGLT2 inhibitor based treatment group only and remained significant after adjustment for the change in systolic BP and the change in heart rate (r = 0.422, p = 0.018). No such correlation was observed between the change in eGFR and the change in PWV in either treatment group. CONCLUSIONS: Our main finding is that after initiating a SGLT2 inhibitor based therapy an exaggerated decline in mGFR was related with improved vascular compliance of large arteries reflecting the pharmacologic effects of SGLT2 inhibitor in the renal and systemic vascular bed. Second, in a single patient with T2D, eGFR may not be an appropriate parameter to assess the true change of renal function after receiving SGLT2 inhibitor based therapy. TRIAL REGISTRATION: clinicaltrials.gov (NCT02752113).


Subject(s)
Benzhydryl Compounds , Diabetes Mellitus, Type 2 , Glomerular Filtration Rate , Glucosides , Kidney , Linagliptin , Pulse Wave Analysis , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Glomerular Filtration Rate/drug effects , Male , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/diagnosis , Middle Aged , Female , Benzhydryl Compounds/therapeutic use , Benzhydryl Compounds/adverse effects , Aged , Treatment Outcome , Kidney/drug effects , Kidney/physiopathology , Glucosides/therapeutic use , Glucosides/adverse effects , Time Factors , Linagliptin/therapeutic use , Linagliptin/adverse effects , Metformin/therapeutic use , Insulin , Diabetic Nephropathies/physiopathology , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/drug therapy , Vascular Stiffness/drug effects , Drug Therapy, Combination , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Biomarkers/blood , Clinical Relevance , Sodium-Glucose Transporter 2
11.
Medicina (Kaunas) ; 60(5)2024 May 20.
Article in English | MEDLINE | ID: mdl-38793020

ABSTRACT

We present the case of a 51-year-old male with known congestive heart failure and acute myocarditis who presented to the emergency department (ED) with swollen testicles and urinary symptoms two weeks after the initiation of sodium glucose cotransporter 2 (SGLT2) inhibitor treatment. Abdominal and pelvic computed tomography (CT) scan was consistent with the diagnosis of Fournier's gangrene (FG). Intravenous antibiotics were administered and surgical exploratory intervention and excision of necrotic tissue were performed, stopping the evolution of necrotizing fasciitis. FG, a reported adverse event, may rarely occur when SGLT2 inhibitors are administered in patients with diabetes. To our knowledge, there have been no reported cases of FG in Romania since SLGT2 inhibitors were approved. The distinguishing feature of this case is that the patient was not diabetic, which emphasizes that patients without diabetes who are treated for heart failure with SGLT2 inhibitors may also be at risk of developing genitourinary infections. The association of predisposing factors may have contributed to the development of FG in this case and even though the benefits of SGLT2 inhibitors outweigh the risks, serious adverse events need to be voluntarily reported in order to intervene promptly, verify the relationship, and minimize the risk of bias.


Subject(s)
Fournier Gangrene , Sodium-Glucose Transporter 2 Inhibitors , Humans , Fournier Gangrene/chemically induced , Male , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Middle Aged , Heart Failure , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Tomography, X-Ray Computed
12.
Cardiovasc Diabetol ; 23(1): 157, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715111

ABSTRACT

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) and SGLT1 inhibitors may have additional beneficial metabolic effects on circulating metabolites beyond glucose regulation, which could contribute to a reduction in the burden of cerebral small vessel disease (CSVD). Accordingly, we used Mendelian Randomization (MR) to examine the role of circulating metabolites in mediating SGLT2 and SGLT1 inhibition in CSVD. METHODS: Genetic instruments for SGLT1/2 inhibition were identified as genetic variants, which were both associated with the expression of encoding genes of SGLT1/2 inhibitors and glycated hemoglobin A1c (HbA1c) level. A two-sample two-step MR was used to determine the causal effects of SGLT1/2 inhibition on CSVD manifestations and the mediating effects of 1400 circulating metabolites linking SGLT1/2 inhibition with CSVD manifestations. RESULTS: A lower risk of deep cerebral microbleeds (CMBs) and small vessel stroke (SVS) was linked to genetically predicted SGLT2 inhibition. Better white matter structure integrity was also achieved, as evidenced by decreased mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), as well as lower deep (DWMH) and periventrivular white matter hyperintensity (PWMH) volume. Inhibiting SGLT2 could also lessen the incidence of severe enlarged perivascular spaces (EPVS) located at white matter, basal ganglia (BG) and hippocampus (HIP). SGLT1 inhibition could preserve white matter integrity, shown as decreased MD of white matter and DWMH volume. The effect of SGLT2 inhibition on SVS and MD of white matter through the concentration of 4-acetamidobutanoate and the cholesterol to oleoyl-linoleoyl-glycerol (18:1 to 18:2) ratio, with a mediated proportion of 30.3% and 35.5% of the total effect, respectively. CONCLUSIONS: SGLT2 and SGLT1 inhibition play protective roles in CSVD development. The SGLT2 inhibition could lower the risk of SVS and improve the integrity of white matter microstructure via modulating the level of 4-acetamidobutanoate and cholesterol metabolism. Further mechanistic and clinical studies research are needed to validate our findings.


Subject(s)
Biomarkers , Cerebral Small Vessel Diseases , Mendelian Randomization Analysis , Sodium-Glucose Transporter 1 , Sodium-Glucose Transporter 2 Inhibitors , Sodium-Glucose Transporter 2 , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sodium-Glucose Transporter 1/genetics , Sodium-Glucose Transporter 1/antagonists & inhibitors , Sodium-Glucose Transporter 1/metabolism , Cerebral Small Vessel Diseases/genetics , Cerebral Small Vessel Diseases/diagnostic imaging , Cerebral Small Vessel Diseases/drug therapy , Cerebral Small Vessel Diseases/blood , Cerebral Small Vessel Diseases/metabolism , Risk Factors , Sodium-Glucose Transporter 2/metabolism , Sodium-Glucose Transporter 2/genetics , Biomarkers/blood , Risk Assessment , Glycated Hemoglobin/metabolism , Pharmacogenomic Variants , Treatment Outcome , Phenotype , Cerebral Hemorrhage/genetics , Cerebral Hemorrhage/chemically induced , Cerebral Hemorrhage/epidemiology , Protective Factors , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Genetic Predisposition to Disease
13.
Am J Cardiovasc Drugs ; 24(3): 455-464, 2024 May.
Article in English | MEDLINE | ID: mdl-38691312

ABSTRACT

PURPOSE: The American Heart Association recommended sodium-glucose cotransporter-2 inhibitors (SGLT2i) for the management of heart failure with preserved ejection fraction (HFpEF). However, little is known about their real-world in-class comparative safety in patients with HFpEF. We aimed to assess the comparative safety of SGLT2i in the risk of urinary tract infection (UTI) or genital infection separately or as a composite outcome among patients with HFpEF. METHODS: This cohort study using MarketScan® Commercial and Medicare supplemental databases (2012-2020) included patients aged ≥ 18 years with a diagnosis of HFpEF who initiated SGLT2i therapy. Three pairwise comparison groups were established: cohort 1, dapagliflozin versus canagliflozin; cohort 2, empagliflozin versus canagliflozin; and cohort 3, dapagliflozin versus empagliflozin. After stabilized inverse probability treatment weighting, Cox proportional hazards regression was used to compare the risk of UTI or genital infection separately or as a composite outcome in each cohort. RESULTS: The risk of the composite outcome did not significantly differ between canagliflozin and dapagliflozin (adjusted hazard ratio [aHR] 0.64; 95% confidence interval [CI] 0.36-1.14) or between empagliflozin and canagliflozin (aHR 1.25; 95% CI 0.77-2.05). Similarly, there was no evidence of difference between dapagliflozin and empagliflozin in this risk (aHR 0.76; 95% CI 0.48-1.21). The results of analyses separately assessing UTI or genital infection were similar. CONCLUSIONS: There was no significant difference in the risk of UTI or genital infection among patients with HFpEF who initiated canagliflozin, dapagliflozin, or empagliflozin.


Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are used for the management of heart failure with preserved ejection fraction (HFpEF). It is important to assess their comparative risk of urinary tract infection (UTI) or genital infection among patients with HFpEF. We compared patients with HFpEF using SGLT2i in three pairwise groups: cohort 1, dapagliflozin versus canagliflozin; cohort 2, empagliflozin versus canagliflozin; and cohort 3, dapagliflozin versus empagliflozin. We found that there was no significant difference in the risk of genitourinary infections including UTI or genital infections among dapagliflozin, empagliflozin, and canagliflozin.


Subject(s)
Benzhydryl Compounds , Canagliflozin , Glucosides , Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Stroke Volume , Urinary Tract Infections , Humans , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Heart Failure/drug therapy , Female , Male , Benzhydryl Compounds/adverse effects , Benzhydryl Compounds/therapeutic use , Aged , Canagliflozin/adverse effects , Canagliflozin/therapeutic use , Urinary Tract Infections/drug therapy , Middle Aged , Glucosides/adverse effects , Glucosides/therapeutic use , Cohort Studies , Stroke Volume/drug effects , Reproductive Tract Infections/chemically induced , Reproductive Tract Infections/epidemiology , Retrospective Studies , Aged, 80 and over
14.
Expert Rev Clin Pharmacol ; 17(5-6): 515-524, 2024.
Article in English | MEDLINE | ID: mdl-38733378

ABSTRACT

INTRODUCTION: Sodium glucose cotransporter-2 inhibitors (SGLT2is) are an emerging class of drugs with wide indications. Controversial evidence exists regarding the risk of urinary tract infection (UTI) and genital infections (GI) with SGLT2is paving way for undertaking this network meta-analysis and meta-regression study. METHODS: Data from randomized trials evaluating SGLT2is reporting the number of patients with UTI and GI were included. Odds ratios (OR) with 95% confidence intervals (95% CI) were the effect estimates. Meta-regression analysis identified risk factors. Number needed to harm (NNH) was estimated. RESULTS: Two hundred and sixty-four articles were included [UTI (213 studies; 150,140 participants) and GI (188 studies; 121,275 participants)]. An increased risk of UTI (OR: 1.11; 95% CI: 1.06, 1.16) and GI (OR: 3.5, 95% CI: 3.1, 3.9) was observed. Men showed a lower risk of UTI (OR: 0.2; 95% CI: 0.2, 0.3) and GI (OR: 0.4; 95% CI: 0.4, 0.5). Meta-regression analyses revealed BMI ≥ 30 kg/m2 and duration of SGLT2i treatment for ≥6 months as risk factors. NNH was 16 for UTI and 25 for GI. CONCLUSION: SGLT2is increase the risk of UTI and GI that needs to be incorporated in the treatment guidelines with precautions in high-risk patients. PROSPECTIVE PROTOCOL REGISTRATION: https://osf.io/5fwyk.


Subject(s)
Randomized Controlled Trials as Topic , Reproductive Tract Infections , Sodium-Glucose Transporter 2 Inhibitors , Urinary Tract Infections , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/administration & dosage , Humans , Urinary Tract Infections/drug therapy , Risk Factors , Male , Reproductive Tract Infections/chemically induced , Reproductive Tract Infections/epidemiology , Female , Network Meta-Analysis , Sex Factors , Regression Analysis , Diabetes Mellitus, Type 2/drug therapy
17.
J Cardiovasc Pharmacol Ther ; 29: 10742484241252474, 2024.
Article in English | MEDLINE | ID: mdl-38711298

ABSTRACT

INTRODUCTION: Sodium-glucose cotransporter- 2 (SGLT2) inhibitors have become a cornerstone in heart failure (HF), Type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD) management. In the current retrospective study, we aimed to assess efficacy and safety of SGLT2 inhibitors early following acute myocardial infarction (AMI). METHODS: Patients with T2DM hospitalized for AMI in 2017-2020 were divided according to SGLT2 inhibitors therapy status on discharge (with vs without therapy). Primary outcome was defined as a composite of hospitalizations for HF, recurrent AMI, and cerebrovascular accident (CVA). Secondary outcomes included hospitalizations for any cause, total cumulative number of hospitalizations, and all-cause mortality. RESULTS: A total of 69 patients (mean age 59.2 ± 8.2 years) with AMI discharged with SGLT2 inhibitors were compared to 253 patients (mean age 62.5 ± 9.8) with no SGLT2 inhibitors. During the first year post-AMI, 4 (5.8%) patients in the treatment group and 16 (6.3%) in the control group were hospitalized for CV events (p = 1.0). Patients in the SGLT2 inhibitors group had lower rates of hospitalization for any cause (31.9% vs 47.8%, P = 0.02), with no change in mortality (0% vs 3.6%, P = 0.21). After multivariate regression analysis, only female gender was associated with increased risk for readmission, mainly due to urinary tract infections. No events of diabetic ketoacidosis (DKA) or limb amputation were reported. CONCLUSIONS: We found that early initiation of SGLT2 inhibitors in T2DM patients following AMI is safe and decreases the risk of hospitalization for any cause.


Subject(s)
Diabetes Mellitus, Type 2 , Myocardial Infarction , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Retrospective Studies , Male , Female , Middle Aged , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/mortality , Aged , Myocardial Infarction/mortality , Treatment Outcome , Time Factors , Risk Factors , Risk Assessment , Hospitalization , Recurrence , Stroke/mortality
18.
Circulation ; 149(23): 1789-1801, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38583093

ABSTRACT

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) consistently improve heart failure and kidney-related outcomes; however, effects on major adverse cardiovascular events (MACE) across different patient populations are less clear. METHODS: This was a collaborative trial-level meta-analysis from the SGLT2i Meta-analysis Cardio-Renal Trialists Consortium, which includes all phase 3, placebo-controlled, outcomes trials of SGLT2i across 3 patient populations (patients with diabetes at high risk for atherosclerotic cardiovascular disease, heart failure [HF], or chronic kidney disease). The outcomes of interest were MACE (composite of cardiovascular death, myocardial infarction , or stroke), individual components of MACE (inclusive of fatal and nonfatal events), all-cause mortality, and death subtypes. Effect estimates for SGLT2i versus placebo were meta-analyzed across trials and examined across key subgroups (established atherosclerotic cardiovascular disease, previous myocardial infarction, diabetes, previous HF, albuminuria, chronic kidney disease stages, and risk groups). RESULTS: A total of 78 607 patients across 11 trials were included: 42 568 (54.2%), 20 725 (26.4%), and 15 314 (19.5%) were included from trials of patients with diabetes at high risk for atherosclerotic cardiovascular disease, HF, or chronic kidney disease, respectively. SGLT2i reduced the rate of MACE by 9% (hazard ration [HR], 0.91 [95% CI, 0.87-0.96], P<0.0001) with a consistent effect across all 3 patient populations (I2=0%) and across all key subgroups. This effect was primarily driven by a reduction in cardiovascular death (HR, 0.86 [95% CI, 0.81-0.92], P<0.0001), with no significant effect for myocardial infarction in the overall population (HR, 0.95 [95% CI, 0.87-1.04], P=0.29), and no effect on stroke (HR, 0.99 [95% CI, 0.91-1.07], P=0.77). The benefit for cardiovascular death was driven primarily by reductions in HF death and sudden cardiac death (HR, 0.68 [95% CI, 0.46-1.02] and HR, 0.86 [95% CI, 0.78-0.95], respectively) and was generally consistent across subgroups, with the possible exception of being more apparent in those with albuminuria (Pinteraction=0.02). CONCLUSIONS: SGLT2i reduce the risk of MACE across a broad range of patients irrespective of atherosclerotic cardiovascular disease, diabetes, kidney function, or other major clinical characteristics at baseline. This effect is driven primarily by a reduction of cardiovascular death, particularly HF death and sudden cardiac death, without a significant effect on myocardial infarction in the overall population, and no effect on stroke. These data may help inform selection for SGLT2i therapies across the spectrum of cardiovascular-kidney-metabolic disease.


Subject(s)
Cardiovascular Diseases , Sodium-Glucose Transporter 2 Inhibitors , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Humans , Cardiovascular Diseases/mortality , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/complications , Female , Male , Treatment Outcome , Aged
19.
Cancer Sci ; 115(6): 2059-2066, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38572526

ABSTRACT

Patients with type 2 diabetes (T2D) are at a higher risk of developing renal cell carcinoma (RCC) than the general population. In vitro and in vivo investigations of the effects of sodium glucose cotransporter-2 inhibitors (SGLT2I) have shown a significantly reduced risk of RCC. However, the impact of these drugs on the incidence of RCC in the human population is unclear. This study aimed to examine the association between SGLT2I use and RCC risk in patients with T2D. We undertook a nationwide retrospective cohort study using the Health and Welfare Data Science Center database (2016-2020). The primary outcome was the risk of incident RCC by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression modeling was applied to analyze the association between SGLT2I use and RCC risk in patients with T2D. In a cohort of 241,772 patients with T2D who were using SGLT2Is and 483,544 participants who were not, 220 and 609 RCC cases, respectively, were recorded. The mean follow-up period of the study subjects was 2 years. There was a decreased risk of RCC for SGLT2I users after adjusting for the index year, sex, age, comorbidities, and concurrent medication (adjusted HR 0.68; 95% CI, 0.58-0.81). The sensitivity test for the propensity score 1:1-matched analyses showed similar results (adjusted HR 0.67; 95% CI, 0.55-0.81). The subgroup analysis revealed consistent results for sex, age (<70 years), and comorbidity with chronic kidney disease. The present study indicates that SGLT2I therapy significantly decreases RCC risk in patients with T2D. This finding was also consistent among the sensitivity test and subgroup analysis for those with or without chronic kidney disease/hypertension.


Subject(s)
Carcinoma, Renal Cell , Diabetes Mellitus, Type 2 , Kidney Neoplasms , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Male , Female , Middle Aged , Kidney Neoplasms/drug therapy , Retrospective Studies , Aged , Incidence , Adult , Proportional Hazards Models , Risk Factors
20.
J Am Coll Cardiol ; 83(16): 1568-1578, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38631776

ABSTRACT

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to reduce adverse cardiovascular events in patients with type 2 diabetes mellitus, all-cause mortality, and heart failure hospitalization in patients with heart failure, as well as adverse renal outcomes. However, concerns regarding the heightened risk of genitourinary (GU) infections, particularly urinary tract infections, remain a significant barrier to their wider adoption. Addressing these misconceptions using existing evidence is needed to ensure proper risk-benefit assessment and optimal utilization of this efficacious therapy. This review aims to provide a balanced perspective on the evidence-based cardiovascular and renal benefits of SGLT2is and the associated risk of GU infections. We also summarize and propose clinical practice considerations for SGLT2i-associated GU infections focusing on patients with cardiovascular disease.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Heart Failure , Hypoglycemic Agents , Sodium-Glucose Transporter 2 Inhibitors , Urinary Tract Infections , Humans , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/etiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Heart Failure/drug therapy , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Urinary Tract Infections/chemically induced , Urinary Tract Infections/complications , Urinary Tract Infections/drug therapy
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