ANTI-INFLAMMATORY EFFECTS AND PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA (PPAR GAMMA)-ACTIVATING PROPERTIES OF THE ANGIOTENSIN TYPE 1 RECEPTOR BLOCKER TELMISARTAN IN PATIENTS

Abstract

Objective: Metabolic syndrome (MetS) is a collection of disorders including diabetes, hypertension, obesity, and dyslipidemia that increase the risk of cardiovascular diseases and mortality. Several studies have discovered that, in addition to its angiotensin receptor blocker activity, telmisartan is a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR gamma), which is a nuclear receptor involved in the regulation of metabolic homeostasis. Evidence also exists that activators of PPAR exert anti-inflammatory, anti-oxidative, and anti proliferative effects on vascular walls. Therefore through PPAR gamma modulating activity, telmisartan can be a valuable agent for treating MetS. Design and method: The PubMed, EMBASE databases and Cochrane Central of Controlled Trials were searched through October 2021. We pooled data extracted from the included studies using the standardized mean difference (SMD). Study-specific estimates were combined using inverse variance-weighted averages of SMDs in both fixed- and random-effects models. Heterogeneity was evaluated using Cochran’s Q- and the I2-test. GRADE assess the study’s quality. All analyses were conducted using StatsDirect statistical software Version 2.8.0. Results: A total of 582 patients were enrolled in the 11 included randomized clinical trials (RCTs). The pooled analysis revealed significant reduction in the percent changes of homeostasis model assessment index (HOMA) (SMD = -0.24; 95% CI: -0.40 to -0.07; p = 0.0036), changes of fasting glucose (mg/dL) (SMD = -0.49; 95% CI: -0.94 to 0.05; p = 0.0283), insulin (mU/mL) (SMD = -0.21; 95% CI: -0.38 to -0.05; p = 0.0084), and a significant increase in percent changes of adiponectin (umg/mL) (SMD = 0.63; 95% CI: 0.34 to 0.92; p < 0.0001),among patients with metabolic syndrome randomized to telmisartan versus control therapy. There was minimal trial heterogeneity in the analyses for HOMA index (I2 = 21.1%), insulin (I2 = 0%) and adiponectin levels (I2 = 0.1%). However, there was considerable heterogeneity in the analysis for fasting glucose (I2 = 83.6%). Conclusions: Our study suggests that the PPAR gamma modulating activity of telmisartan has the potential to be a valuable therapeutic agent for treating MetS.