Metabolic research

Retatrutide — triple receptor agonism and the glucagon contribution to metabolic therapy

Retatrutide adds glucagon receptor agonism to the GLP-1R and GIPR dual agonist framework, producing Phase 2 weight loss data of approximately 24% at 48 weeks. This article covers why glucagon receptor activation — counterintuitive for a metabolic compound — contributes to fat loss through thermogenesis and hepatic lipid clearance.

Insulin resistance: mechanisms of metabolic dysfunction and intervention targets

Insulin resistance is the central defect in type 2 diabetes and metabolic syndrome, driven by ectopic lipid accumulation, mitochondrial dysfunction, inflammatory signalling, and endoplasmic reticulum stress. This review covers the molecular mechanisms and the peptide and metabolic interventions that target them.

GLP-1 receptor agonists and cardiovascular outcomes: evidence from MACE trials

GLP-1 receptor agonists demonstrate significant reductions in major adverse cardiovascular events (MACE) across multiple large randomised trials. This review examines the LEADER, SUSTAIN-6, REWIND, and SELECT trial data and the proposed mechanisms behind cardiovascular protection.

Tirzepatide dual agonism — the GIP paradox and why adding a second incretin works

Tirzepatide co-activates GLP-1R and GIPR simultaneously, producing weight loss and glycaemic outcomes that exceed GLP-1 monotherapy. The GIP contribution is paradoxical — GIPR agonism and antagonism both appear to reduce body weight — and this article covers the current mechanistic explanation and the central GIP receptor hypothesis.

Semaglutide weight loss mechanisms — why albumin acylation changed metabolic pharmacology

Semaglutide's once-weekly dosing and exceptional weight loss outcomes stem from two engineering decisions: DPP-IV-resistant amino acid substitution and C18 fatty diacid acylation enabling albumin binding. This article covers the half-life extension chemistry and the defended body weight setpoint biology that explains the STEP trial outcomes.

GLP-1 receptor agonists — the three-part mechanism behind glucagon-like peptide therapy

GLP-1 receptor agonists produce weight loss and glycaemic control through three concurrent mechanisms: glucose-dependent insulin secretion, gastric emptying delay, and central appetite suppression via hypothalamic GLP-1 receptors. This article covers all three and why their combination is pharmacologically unique.