Injectable PCSK9 inhibitors effectively lower LDL-C levels in patients with hypercholesterolemia; however, their high cost and requirement for parenteral administration limit their widespread use. Ora Show more
Injectable PCSK9 inhibitors effectively lower LDL-C levels in patients with hypercholesterolemia; however, their high cost and requirement for parenteral administration limit their widespread use. Oral PCSK9 inhibitors have emerged as a convenient alternative. This review and meta-analysis of the literature evaluate the effectiveness and safety of oral PCSK9 inhibitor treatment for adults with hypercholesterolemia. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched through September 2025 for randomized controlled trials comparing oral PCSK9 inhibitors with placebo. The primary outcome was percentage change in LDL-C, with secondary lipid and safety outcomes. We used Cochrane RoB 2.0 tool to assess risk of bias, and pooled estimates were calculated using a random-effects model. Certainty of evidence was evaluated with GRADE. From 1253 records, 3 trials were included. Participants were mostly men, aged 61-65 years, with elevated baseline LDL-C. Oral PCSK9 inhibitors significantly reduced LDL-C and ApoB in a dose-dependent manner and achieved modest reductions in triglycerides (MD -6.56 mg/dL; 95% CI, -12.30 to -0.83) and total cholesterol (MD -25.25 mg/dL; 95% CI, -30.67 to -19.83). Effects on lipoprotein(a) were inconsistent. Adverse events (RR 1.06; 95% CI, 0.91-1.23) and serious adverse events (RR 1.32; 95% CI, 0.41-4.26) were comparable with placebo. According to our review, oral PCSK9 inhibitors are a promising therapeutic option for treating hypercholesterolemia because of their potent lipid-lowering effects and an overall favorable safety profile. However, more trials are needed to confirm their impact on cardiovascular outcomes. Show less
Adenylate cyclases (ADCYs) catalyze the conversion of ATP to cAMP, an important co-factor in energy homeostasis. Giving ADCYs role in obesity, diabetes and inflammation, we questioned whether calcium- Show more
Adenylate cyclases (ADCYs) catalyze the conversion of ATP to cAMP, an important co-factor in energy homeostasis. Giving ADCYs role in obesity, diabetes and inflammation, we questioned whether calcium-stimulated ADCY isoforms may be variably detectable in human plasma. We report the results of a cross-sectional study assessing circulating levels of functional ADCY1, -3 and -8 in patients with T2D vs. non-diabetic (ND) controls in association with obesity. ADCY1 levels exhibited no significant change between ND and T2D groups. ADCY3 levels were lower in obese individuals, albeit not statistically significantly. In contrast, ADCY8 plasma levels were significantly higher in obese and T2D patients compared to controls ( Show less