Jewjitsu Peptides: Three new reports on tirzepatide, a glutathione peptide crystal, and insulin-linked diastolic risk

Tirzepatide study: The authors report a multicenter retrospective cohort analysis using the TriNetX US Collaborative Network that emulated a target trial in adults ≥18 years who were overweight or obese and initiated tirzepatide, GLP-1 receptor agonists (GLP-1RAs), or other anti-obesity medications between January 2022 and December 2024. Propensity-score 1:1 matching was applied to balance demographics, BMI, comorbidities, and socioeconomic variables. After matching the cohorts, tirzepatide use was associated with a lower hazard of incident carpal tunnel syndrome (CTS) versus GLP-1RAs (HR 0.82; 95% CI 0.71–0.95), with no significant difference in CTS surgery in that comparison. Versus other anti-obesity medications, tirzepatide was associated with reduced hazards of both CTS (HR 0.75; 95% CI 0.65–0.85) and CTS surgery (HR 0.64; 95% CI 0.44–0.94). The investigators performed sensitivity and subgroup analyses and reported IRB exemption.

Glutathione peptide piezoelectric material: This report describes a natural glutathione (GSH) tripeptide that self-assembles into an antiparallel staggered supramolecular crystalline stacking. Density functional theory calculations in the study indicated a maximum piezoelectric coefficient of 64.3 pC N-1 for the GSH self-assemblies, described as one of the highest predicted among peptide-based assemblies. The authors built a GSH assembly-based piezoelectric nanogenerator that produced an open-circuit voltage of 5.02 V under an external force of 45 N and demonstrated stability over 6,000 continuous press–release cycles. They also report a GSH crystal-based self-powered sensor prototype for monitoring human joint bending, positioning this work as an advance in biomolecule-based piezoelectric supramolecular materials.

Endogenous insulin and diastolic dysfunction: In a community-based cohort drawn from the Olmsted County Heart Function Study, the authors analyzed 1,191 participants who had baseline and 4-year echocardiography and measured fasting insulin and HOMA-IR (homeostatic model assessment of insulin resistance). Diastolic dysfunction (DD) progression occurred in 7.5% of participants. Baseline fasting insulin and HOMA-IR strongly predicted DD progression (P < 0.001). In multivariable analysis, each 1-SD increase in log-transformed insulin was associated with increased odds of progression (OR 1.65; 95% CI 1.33–2.07), and HOMA-IR showed a similar association (OR 1.66; 95% CI 1.34–2.08). Secondary analyses in 2,030 participants with longer follow-up found that elevated insulin and HOMA-IR independently predicted all-cause and cardiovascular mortality (examples reported: insulin HR 1.11 per 1-SD [95% CI 1.02–1.21] for all-cause mortality and HR 1.16 [95% CI 1.02–1.33] for cardiovascular mortality). The authors frame metabolic dysregulation as a potential driver of myocardial stiffening before diabetes onset.