Overview
GLP-1, or Glucagon-Like Peptide-1, is a naturally occurring peptide hormone produced in the intestinal L-cells of the gut in response to food intake. It belongs to the incretin family of peptides, which are known for their role in regulating insulin secretion and glucose metabolism in biological systems. As a 30-amino acid peptide derived from the proglucagon protein, GLP-1 has been the subject of considerable scientific interest due to its involvement in metabolic signaling pathways. Researchers have investigated GLP-1 in the context of conditions such as metabolic dysfunction, cardiovascular physiology, and autonomic nervous system activity, with published studies also exploring its potential relevance to biological aging and cardiac health. GLP-1 is available for research purposes only and is not intended for human use or consumption.
Research & Bioactivity
GLP-1 (glucagon-like peptide-1) is an endogenous peptide hormone that researchers have studied extensively in the context of metabolic regulation, appetite signaling, and cardiovascular physiology. Studies have examined its role in glucose homeostasis and its interactions with other gut-derived hormones, including research investigating circulating GLP-1 levels in conditions such as postural orthostatic tachycardia syndrome and their associations with hemodynamic and gastrointestinal parameters. Research has also investigated GLP-1 receptor agonism in relation to cardiac biology, including atrial lymphangiogenesis and the pathophysiology of atrial fibrillation, as well as in models of obesity-related heart failure. In randomized controlled trial settings, researchers have explored how GLP-1 receptor agonists may influence biological aging markers, including epigenetic aging clocks, in populations such as adults with HIV-associated metabolic changes. Additionally, animal and pharmacological studies have examined how GLP-1 signaling interacts with the endocannabinoid system and gut-brain communication pathways relevant to energy balance and food intake. Collectively, these research efforts reflect the broad scientific interest in GLP-1 as a subject of study across metabolic, cardiovascular, and neuroendocrine biology.
Published Research
Gut hormones in POTS and their relation to hemodynamic parameters and gastrointestinal symptoms.
Tufvesson H, Roth B, Johansson M, Hamrefors V, Fedorowski A, et al. — 2026
Postural orthostatic tachycardia syndrome (POTS) is associated with multiple autonomic symptoms, including gastrointestinal (GI) complaints, and has been linked to insulin resistance. We aimed to explore HbA1c, circulating metabolic hormones (insulin, C-peptide, GIP, GLP-1, glucagon, leptin, and peptide YY) and cortisol, and their associations with hemodynamic parameters and GI symptoms in POTS. Two POTS cohorts were studied and compared with matched controls. In the fasting cohort, blood samples were drawn in 42 patients and 41 controls, followed by active standing tests with measurement of pulse and blood pressure (BP) in supine and standing positions. In the non-fasting cohort, questionnaires assessed GI symptoms and HbA1c was measured in 43 patients and 52 controls. Fasting C-peptide and insulin levels correlated with BP in POTS (q = 0.002) but not in controls. Fasting insulin tended to be higher in POTS but was not statistically significant after adjustment for BMI (β = 6.85; 95% CI: -1.04-14.74; p = 0.085). Morning cortisol was comparable between groups. In the non-fasting cohort, HbA1c and metabolic hormones were comparable between groups, with no associations with GI symptoms. Together, these findings suggest a potential link between insulin-related pathways and BP regulation in POTS. Future studies are warranted to further investigate insulin dynamics in POTS.
Kynurenic acid mediates epicardial fat-induced lymphatic metabolic dysfunction in atrial fibrillation.
Takahashi M, Abe I, Yoshida N, Katoh D, Fujita D, et al. — 2026
Atrial fibrillation represents a prevalent cardiac arrhythmia whose pathogenic mechanisms remain incompletely understood. Here, we identify impaired atrial lymphangiogenesis as a critical determinant in atrial fibrillation pathogenesis. Analysis of human left atrial appendage specimens reveals decreased lymphatic vessel density in atrial fibrillation patients compared to those in sinus rhythm. Mechanistically, we demonstrate that epicardial adipose tissues from atrial fibrillation patients secrete kynurenic acid, which acts via GPR35 to disrupt lymphatic endothelial cell metabolism and mitochondrial homeostasis, ultimately promoting endothelial-to-mesenchymal transition. Using an organotypic culture system, we show that epicardial adipose tissue -derived factors directly impair lymphatic vessel formation. In vivo studies utilizing angiotensin II-induced and high-fat diet male mouse models confirm the critical role of lymphatic dysfunction in atrial fibrillation susceptibility. Therapeutic interventions promoting lymphangiogenesis, either through VEGFC administration or weight loss intervention by LY3437943 (the novel triple GIP, GLP-1, and glucagon receptor agonist), significantly attenuate atrial fibrillation inducibility. These findings establish lymphatic dysfunction as a novel pathogenic mechanism in atrial fibrillation and highlight lymphatic vessel formation as a promising therapeutic target.
Semaglutide slows epigenetic aging in a randomized trial of HIV-associated lipohypertrophy.
Corley MJ, Dwaraka VB, Pang AP, Labbato D, Smith R, et al. — 2026
Glucagon-like peptide-1 (GLP-1) receptor agonists have attracted interest as gerotherapeutics, yet clinical-trial evidence for their effects on biological aging is lacking. We report a post hoc exploratory epigenetic age analysis of a 32-week, randomized, double-blind, placebo-controlled phase 2b trial (NCT04019197) of semaglutide in adults with human immunodeficiency virus (HIV)-associated lipohypertrophy (semaglutide n = 45; placebo n = 39). The parent trial's primary endpoint was change in visceral adipose tissue, with secondary cardiometabolic and body-composition endpoints; epigenetic aging was not pre-specified. To address this gap, we profiled peripheral-blood DNA methylation (DNAm) at baseline and week 32 to assess semaglutide versus placebo on first-, second-, and third-generation epigenetic aging measures. In adjusted analyses, semaglutide reduced epigenetic aging across multiple second- and third-generation clocks, including PhenoAge ( - 4.9 years/year, p = 0.004), PCGrimAge ( - 3.1, p = 0.007), GrimAge V2 ( - 2.3, p = 0.009), OMICmAge ( - 2.2, p = 0.009), RetroAge ( - 2.2, p = 0.030), and DunedinPACE ( - 0.09 units, 9% slower, p = 0.01). Systems-based clocks showed parallel reductions in inflammation, brain, and heart aging measures. The post hoc design, modest sample size, HIV-specific cohort, and 32-week follow-up limit generalizability. Prospective trials are needed to determine whether GLP-1 receptor agonists can be repurposed as gerotherapeutics.
Inhibition of peripheral CB receptors modulates food intake and metabolic efficiency in obesity independently of the gut-brain vagal axis.
Onimus O, de Almeida C, Bertrand B, Castel J, Mashhour N, et al. — 2026
BACKGROUND AND PURPOSE: Obesity involves profound disruptions in neuronal circuits, neuroendocrine communication and the endocannabinoid system. While global blockade of cannabinoid CB receptors improves metabolism, its clinical use is limited by neuropsychiatric side effects. Peripherally restricted CB receptor antagonists offer a safer alternative, although the neural pathways, specifically the gut-brain vagal axis, mediating their effects remain unclear. EXPERIMENTAL APPROACH: Metabolic and neural effects of peripheral inhibition of CB receptors by JD5037 and AM6545, were assessed in lean and diet-induced obese (DIO) mice. Metabolic parameters were measured using indirect calorimetry, and neuronal activation was mapped by cFos immunoreactivity. Involvement of vagal signalling was examined using subdiaphragmatic vagotomy (SDV) and antagonists of cholecystokinin and glucagon-like peptide-1 (GLP-1) receptors. KEY RESULTS: Inhibition of peripheral CB receptors suppressed food intake and shifted nutrient partitioning toward fatty acid oxidation in DIO, but not lean, mice. Obesity up-regulated CB receptor expression in the nodose ganglia. In DIO mice, peripheral CB receptor inhibition robustly activated satiety-related brainstem (nucleus tractus solitarius, area postrema, parabrachial nucleus) and hypothalamic (arcuate and paraventricular) nuclei. SDV abolished brainstem activation but failed to blunt hypothalamic recruitment or the anorexigenic and metabolic benefits. Antagonists of cholecystokinin or GLP-1 receptors did not prevent the feeding-suppressive effects of JD5037. CONCLUSIONS AND IMPLICATIONS: Our findings revealed a dual-mechanism model: vagal pathways mediated brainstem engagement, while hypothalamic recruitment and metabolic improvements occurred via vagal-independent signalling. Thus, peripherally-restricted CB receptor antagonists indirectly engage central homeostatic circuits, supporting their therapeutic potential for obesity even in conditions with impaired vagal signalling.
Cost-effectiveness and budget-impact analysis of tirzepatide in heart failure with preserved ejection fraction and obesity in the German health-care system.
Estler B, Fröhlich H, Täger T, Heins J, Frey N, et al. — 2026
BACKGROUND: Heart failure with preserved ejection fraction is common, obesity-related, and associated with high symptom burden and healthcare use. Tirzepatide, a dual GIP/GLP-1 receptor agonist, improved symptoms and outcomes in SUMMIT, but its acquisition cost raises concerns about value and affordability. METHODS: We developed a Markov model comparing tirzepatide versus placebo, both added to standard care, in the SUMMIT population from the German statutory health insurance perspective. The model used monthly cycles over 5 years with four Kansas City Cardiomyopathy Questionnaire clinical summary score-defined health states (Q1-Q4) plus death. Arm-specific transitions and rates of all-cause death and worsening heart failure were derived from SUMMIT. Deterministic and probabilistic sensitivity analyses, including tirzepatide price-reduction scenarios, were conducted to explore parameter uncertainty and price thresholds simultaneously. A prevalence-based budget impact analysis extrapolated results to the German HFpEF-obesity population under alternative eligibility (SUMMIT-like vs broad) and uptake (30%, 50%, 100%) scenarios. RESULTS: Discounted per-patient costs were €5827 (placebo) and €31,052 (tirzepatide), with quality-adjusted life years of 3.539 and 3.638. Tirzepatide generated 0.100 additional quality-adjusted life years at an incremental cost of €25,225, yielding an incremental cost-effectiveness ratio of 252,611€/quality-adjusted life year, with low probability of cost-effectiveness at €100,000/QALY. Five-year incremental spending was ~€1.9-6.2 billion with SUMMIT-like and ~ €3.8-12.6 billion with broad eligibility, depending on uptake. CONCLUSIONS: Tirzepatide provides modest quality-adjusted life year gains at substantially higher costs and, at current price, appears neither cost-effective nor affordable at scale in German care. Substantial price reductions would be required to improve economic attractiveness and budgetary impact.