Effect of Gastric pH on the Pharmacokinetics of Atorvastatin and its Metabolites in Healthy Participants.

Background And Objective: Atorvastatin is dosed in its active acid form although it exists in equilibrium with its inactive lactone form in vivo. Although in vitro atorvastatin acid displays pH-dependent conversion to the lactone metabolite, pharmacokinetic (PK) data on the effect of elevated gastric pH on atorvastatin and major atorvastatin-related species are not currently available. In this dedicated study, we investigated the effect of food and acid-reducing agents on the PK of atorvastatin and its three major metabolites in humans.

Pharmacokinetic and pharmacodynamic properties of the novel basal insulin Fc (insulin efsitora alfa), an insulin fusion protein in development for once-weekly dosing for the treatment of patients with diabetes.

Aim: To assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of basal insulin Fc (BIF; LY3209590), a fusion protein combining a novel single-chain insulin variant together with human IgG2 Fc domain, following single and multiple once-weekly BIF administration.

Materials And Methods: The single ascending dose, 15-day study assessed four BIF doses (5-35 mg) in healthy participants and people with type 2 diabetes (T2D). In the 6-week multiple ascending dose study, people with T2D, previously treated with basal insulin, received insulin glargine daily or a one-time loading dose of BIF followed by 5 weeks of once-weekly dosing (1-10 mg).

Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial.

Background: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, shows a remarkable ability to lower blood glucose, enabling many patients with long-standing type 2 diabetes to achieve normoglycaemia. We aimed to understand the physiological mechanisms underlying the action of tirzepatide in type 2 diabetes.

Methods: This multicentre, randomised, double-blind, parallel-arm, phase 1 study was done at two centres in Germany.

Phaeochromocytoma mimicking scleroderma.

We describe a patient with adrenal phaeochromocytoma who presented with peripheral vasospasm and ischaemia and other manifestations mimicking features of systemic sclerosis, which resolved after resection of the tumor. Phaeochromocytoma should be suspected in patients with features of scleroderma who are negative for auto-antibodies.