Cardiovascular benefits of GLP-1 receptor agonists in patients living with obesity or overweight: a meta-analysis of randomized controlled trials

BACKGROUND: GLP-1 receptor agonists (GLP-1 RAs) have emerged as an effective therapeutic class for weight loss. However, the efficacy of these agents in reducing cardiovascular endpoints among patients living with obesity or overweight is unclear. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing GLP-1 RAs versus placebo in patients with obesity or overweight. We searched PubMed, Cochrane, and Embase databases. A random-effects model was used to calculate risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CIs). RESULTS: A total of 13 RCTs were included, with 30,512 patients. Compared with placebo, GLP-1 RAs reduced systolic blood pressure (MD - 4.76 mmHg; 95% CI - 6.03, - 3.50; p < 0.001; I2 = 100%) and diastolic blood pressure (MD - 1.41 mmHg; 95% CI - 2.64, - 0.17; p = 0.03; I2 = 100%). GLP-1 RA significantly reduced the occurrence of myocardial infarction (RR 0.72; 95% CI 0.61, 0.85; p < 0.001; I2 = 0%). There were no significant differences between groups in unstable angina (UA; RR 0.84; 95% CI 0.65, 1.07; p = 0.16; I2 = 0%), stroke (RR 0.91; 95% CI 0.74, 1.12; p = 0.38; I2 = 0%), atrial fibrillation (AF; RR 0.49; 95% CI 0.17, 1.43; p = 0.19; I2 = 22%), and deep vein thrombosis (RR 0.30; 95% CI 0.06, 1.40; p = 0.13; I2 = 0%). CONCLUSIONS: In patients living with obesity or overweight, GLP-1 RA reduced systolic and diastolic blood pressure and the occurrence of myocardial infarction, with a neutral effect on the occurrence of UA, stroke, AF, and deep vein thrombosis.

Cardiovascular Benefits of GLP-1 Receptor Agonists in Patients Living with Obesity or Overweight: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: GLP-1 receptor agonists (GLP-1 RAs) have emerged as an effective therapeutic class for weight loss. However, the efficacy of these agents in reducing cardiovascular endpoints among patients living with obesity or overweight is unclear. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing GLP-1 RAs versus placebo in patients with obesity or overweight. We searched PubMed, Cochrane, and Embase databases. A random-effects model was used to calculate risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CIs). RESULTS: A total of 13 RCTs were included, with 30,512 patients. Compared with placebo, GLP-1 RAs reduced systolic blood pressure (MD - 4.76 mmHg; 95% CI - 6.03, - 3.50; p < 0.001; I2 = 100%) and diastolic blood pressure (MD - 1.41 mmHg; 95% CI - 2.64, - 0.17; p = 0.03; I2 = 100%). GLP-1 RA significantly reduced the occurrence of myocardial infarction (RR 0.72; 95% CI 0.61, 0.85; p < 0.001; I2 = 0%). There were no significant differences between groups in unstable angina (UA; RR 0.84; 95% CI 0.65, 1.07; p = 0.16; I2 = 0%), stroke (RR 0.91; 95% CI 0.74, 1.12; p = 0.38; I2 = 0%), atrial fibrillation (AF; RR 0.49; 95% CI 0.17, 1.43; p = 0.19; I2 = 22%), and deep vein thrombosis (RR 0.30; 95% CI 0.06, 1.40; p = 0.13; I2 = 0%). CONCLUSIONS: In patients living with obesity or overweight, GLP-1 RA reduced systolic and diastolic blood pressure and the occurrence of myocardial infarction, with a neutral effect on the occurrence of UA, stroke, AF, and deep vein thrombosis. REGISTRATION: PROSPERO identifier number CRD42023475226.

Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy versus Endocrine Therapy Alone for HR-Positive, HER-2-Negative Early Breast Cancer: Meta-Analysis of Phase III Randomized Clinical Trials.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for advanced breast cancer combined with endocrine therapy (ET). The efficacy of CDK4/6 inhibitors plus ET in hormone estrogen-positive, human epidermal growth factor 2-negative (HR+/HER2-) early-stage breast cancer (esBC) is still to be confirmed. METHODS: We performed a systematic review and a meta-analysis to investigate the efficacy of CDK4/6i plus ET in esBC. Main outcomes included invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS). We included only phase III randomized controlled trials. We used RStudio version 4.2.3, and we considered p < 0.05 to be statistically significant. RESULTS: Four studies were selected, including 14,168 patients, of which 7089 were treated with CDK4/6i plus ET and 7079 received ET monotherapy. Regarding patient characteristics, 6828 (48.2%) were premenopausal. Compared with ET alone, iDFS rates (HR 0.81; 95% CI: 0.67, 0.98; p = 0.034) were significantly in favor of CDK4/6 inhibitors plus ET. However, there were no significant differences in DRFS (HR 0.79; 95% CI: 0.58, 1.07; p = 0.132) nor OS (HR 0.96; 95% CI: 0.69, 1.35; p = 0.829). CONCLUSIONS: Our results show that the addition of CDK4/6 inhibitors is associated with a significant benefit for HR+/HER2- esBC patients in iDFS. More studies and longer follow-up are needed to assess overall survival benefits.

The effect of sodium-glucose transporter 2 inhibitors on stroke in patients with type 2 diabetes: A meta-analysis.

OBJECTIVES: To provide an update on the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on stroke in patients with type 2 diabetes (T2D). METHODS: PubMed, Embase, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) comparing SGLT2 inhibitors versus placebo or other therapies in patients with T2D and reporting stroke endpoint. We computed the risk ratios (RRs) to binary endpoints, with 95 % confidence intervals (CIs). RESULTS: A total of 71 RCTs and 105,914 patients were included, of whom 62,488 (59 %) were randomized to the SGLT2 inhibitors group. The follow-up ranged from 12 weeks to 4.2 years. There were no significant differences between groups in all types of stroke (RR 0.96; 95 % CI 0.89-1.04), ischemic stroke (RR 0.89; 95 % CI 0.76-1.04), and transient ischemic attack (RR 0.96; 95 % CI 0.79-1.16). Patients on SGLT2 inhibitors experienced lower rates of hemorrhagic stroke (RR 0.62; 95 % CI 0.39-0.98). In the subgroup analysis of the type of drug, sotagliflozin significantly reduced all types of stroke (RR 0.74; 95 % CI 0.56-0.97). CONCLUSION: In this meta-analysis of 71 RCTs comprising 105,914 patients with T2D, SGLT2 inhibitors were not associated with a reduced risk of stroke and transient ischemic attack compared to placebo or other therapies; however, there was a trend toward reduced risk of hemorrhagic stroke. Among all SGLT2 inhibitors, sotagliflozin significantly reduced the risk of stroke.

Safety and efficacy of sotagliflozin in patients with type II diabetes mellitus and chronic kidney disease: a meta-analysis of randomized controlled trials.

BACKGROUND: Sotagliflozin is a dual sodium-glucose co-transporter 1 and 2 inhibitor that increases glucosuria and natriuresis in patients with type 2 diabetes mellitus (T2DM). However, the safety and efficacy in patients with concomitant chronic kidney disease (CKD) remains unclear. Therefore, we aimed to conduct a meta-analysis to evaluate the current evidence in this regard. METHODS: We searched PubMed, Embase, Cochrane, and Web of Science for randomized controlled clinical trials on the safety and efficacy of Sotagliflozin in patients with T2DM and CKD compared with placebo. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I2 statistics. The study was recorded in PROSPERO registry (CRD42023449631). RESULTS : We included three studies totaling 11,648 patients followed for 15.7 ± 5.9 months. Reduction in HbA1C (mean difference - 0.33%; 95% CI [- 0.54, - 0.11]; p = 0.003; I2 = 100%) and weight (mean difference - 1.01 kg; 95% CI [- 1.17, - 0.86]; p < 0.00001; I2 = 96%) were significantly higher in the Sotagliflozin group compared with placebo. All-cause mortality (RR 0.98; 95% CI [0.81, 1.20]; p = 0.87; I2 = 0%) and major adverse cardiovascular events (RR 0.70; 95% CI [0.40, 1.21]; p = 0.20; I2 = 39%) were not significantly different between groups. However, estimated glomerular filtration rate reduction (mean difference - 0.95; 95% CI [- 1.32, - 0.58]; p < 0.00001; I2 = 98%), genital mycotic infections (RR 2.73; 95% CI [1.96, 3.79]; p < 0.00001; I2 = 0%), diarrhea (RR 1.42; 95% CI [1.24. 1.63]; p < 0.00001; I2 = 0%) and volume depletion (RR 1.31; 95% CI [1.11, 1.56]; p = 0.002; I2 = 0%) were more common with Sotagliflozin. CONCLUSIONS: In patients with T2DM and CKD, Sotagliflozin appears to be effective for glycemic control and weight loss. Although the medication seemed safe concerning mortality and cardiovascular events, it induced estimated glomerular filtration rate reduction, and was associated with a higher risk of genital mycotic infections, diarrhea, and volume depletion.

Mesenchymal-Epithelial Transition Kinase Inhibitor Therapy in Patients with Advanced Papillary Renal-Cell Carcinoma: A Systematic Review and Meta-Analysis.

Papillary subtypes of renal-cell carcinoma (pRCC) represent 10-15% of the cases and commonly have MET alterations. This systematic review and single-arm meta-analysis evaluated MET inhibitor therapy (METi) efficacy and safety in adults with confirmed advanced pRCC. The search strategy included PubMed, Web-of-science, Cochrane, and Scopus. We used the DerSimonian/Laird random effect model for all analyses; p-value < 5% was considered significant, and heterogeneity was assessed with I2. Three clinical trials and six cohort studies were included with 504 patients; 31% were MET-driven. Our pooled analysis demonstrated an objective response rate (ORR) in MET-driven, MET-independent, and overall patients of: 36% (95%CI: 10-62), 0% (95%CI: 0-3), and 21% (95%CI: 1-41), respectively. One-year disease control and progression-free survival rates were, respectively, 70% (95%CI: 52-88) and 15% (95%CI: 10-20). Twelve- and twenty-four-month survival rates were, respectively, 43% (95%CI: 23-64) and 10% (95%CI: 0-30). The prevalence of adverse events of any grade and grades 3-5 were 96% (95%CI: 91-100) and 44% (95%CI: 37-50), respectively. We suggest METi has anti-tumor activity and is tolerable in patients with advanced pRCC.