Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials.

OBJECTIVES: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes. We performed a meta-analysis to assess tirzepatide's weight reduction efficacy and safety. METHODS: We searched PubMed, Embase, and Cochrane for randomized controlled trials published from inception to July 2022, comparing tirzepatide with placebo for the co-primary endpoints of absolute and percent change in weight. Mean difference (MD) and odds ratio (OR) were calculated for continuous and binary outcomes, respectively. Review Manager 5.4.1 and RStudio were used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. RESULTS: Of 397 search results, 6 studies (4036 participants) ranging from 12 to 72 weeks were included. Pooled analysis showed that tirzepatide 5 mg, 10 mg, and 15 mg were more effective than placebo, with MD in body weight of -7.7 kg (95% CI -11.0, -4.4; p < 0.001), -11.6 kg (95% CI -18.8, -4.3; p = 0.002), and -11.8 kg (95% CI -17.4, -6.2; p < 0.001), respectively, and MD in percent change in weight of -8.1% (95% CI -11.0, -5.2; p < 0.001), -11.9% (95% CI -18.1, -5.6; p < 0.001), and -12.4% (95% CI -17.2, -7.5; p < 0.001), respectively. Tirzepatide also reduced BMI and waist circumference. Adverse events were more common with tirzepatide with respect to nausea (OR 4.2; 95% CI 2.4, 7.5; p < 0.001), vomiting (OR 7.0; 95% CI 4.3, 11.4; p < 0.001), and diarrhea (OR 2.8; 95% CI 1.6, 4.9; p < 0.001) (15 mg dose), when compared with placebo. CONCLUSIONS: The results support that tirzepatide leads to substantial weight reduction and constitutes a valuable therapeutic option for weight management, despite an increase in gastrointestinal symptoms. PROTOCOL REGISTRATION: CRD42022348576.

Papel das estatinas na modulação da função endotelial vasomotora na hipertensão e doença coronariana / The role of statins in the modulation of endothelium vasomotor function in hypertension and coronary artery disease

o benefício em longo prazo do tratamento com estatinas naprevenção de eventos coronarianos primários e secundários éindiscutível. Embora uma parte deste benefício esteja ligadaao efeito sobre a redução da circulação de lipoproteínasaterogênicas, outros mecanismos, como a modulação datrombogênese, a redução da inflamação e melhora da funçãoendotelial, têm sido investigados. O efeito da estatina sobrea função endotelial está ligado à sua inibição da produçãode superóxido e sua regulação positiva da síntese do óxidonítrico (NOS) no endotélio. Na prática clínica, o benefíciona função do endotélio depois do tratamento com estatinatem sido observado em uma ampla variedade de condiçõesque incluem a hipertensão arterial sistêmica, doença arterialcrônica e síndrome coronariana aguda. Esta breve revisãoincidirá sobre as principais conclusões relacionadas à terapiacom estatina sobre o tônus arterial sistêmico e doença arterialcoronariana aguda e crônica...

The long-term benefit of statin treatment on the prevention of primary and secondary coronary events is undisputed. Although a proportion of this effect has been linked to its reduction of circulating atherogenic lipoproteins, other mechanisms have been studied such as modulation of thrombogenesis, reduction of inflammation, and improvement of endothelia! function. Its favorable effect on endothelial function is tied to its inhibition of superoxide production and its positive regulation of nitric oxide synthase (NOS) in the endothelium. In the clinica! setting, the gain in endothelia! function after statin treatment has been observed in a wide range of conditions that include systernic hypertension, chronic arterial disease, and acute coronary syndrome. This brief review will focus on the main findings related to statin therapy on the systernic arterial tone and both acute and chronic coronary artery disease...