Glucagon-like peptide-1 (GLP-1) has emerged as a pivotal regulator in the management of glucose homeostasis, glycogen metabolism, and energy balance, positioning it as a critical therapeutic target for addressing obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). GLP-1 receptor agonists (GLP-1RAs) have shown promise for improving glycemic control and reducing weight through appetite regulation, delayed gastric emptying, and energy expenditure modulation. This narrative review explores the mechanisms of GLP-1-mediated glycogen metabolism and energy expenditure, particularly in key tissues—pancreas, liver, skeletal muscle, and adipose tissue. In the pancreas, GLP-1 enhances insulin secretion and beta-cell function. In the liver, it promotes glycogen synthesis via insulin-dependent and potential insulin-independent pathways, involving protein kinase B (AKT) and AMP-activated protein kinase (AMPK) signaling. Skeletal muscle benefits from GLP-1 through increased glucose uptake, AMPK activation, and mitochondrial function, facilitating glycogen storage. In adipose tissue, GLP-1 stimulates brown adipose tissue (BAT) thermogenesis and energy expenditure, contributing to weight loss. This increase in energy expenditure, along with enhanced glycogen metabolism, is a plausible mechanism for the weight loss observed with GLP-1RAs. Despite these advances, significant knowledge gaps remain, particularly regarding the direct hepatic effects of GLP-1, the extent to which it modulates glycogen metabolism in vivo, and its impact on thermogenesis in humans. Future research focusing on both the tissue-specific actions of GLP-1 and its systemic role in energy homeostasis and metabolic regulation will be essential for optimizing its therapeutic potential.

Background: This study aimed to further explore the application of genetic risk assessments in 24 metabolic bariatric surgery (MBS) patients to predict weight loss outcomes three years after the procedure. Methods: Participants were assessed using the Genetic Addiction Risk Severity (GARS) test, which evaluates neurogenic polymorphisms linked to addiction and reward deficiency. Genetic and psychosocial data collected prior to surgery were analyzed in relation to post-operative weight loss measures, including weight change, body mass index (BMI), percentage of total weight loss (%TWL), and percentage of expected weight loss (%EWL). The analysis examined associations between specific genetic risk alleles, weight-related outcomes at three to four years post-surgery, and psychosocial trait scores. Results: Spearman’s correlations revealed that the DRD2 risk allele is negatively correlated with 3-year BMI (r_s = −0.481, p < 0.05, 95% CI: –0.746 to –0.083). One-way ANOVA indicated that there is a significant difference in 3-year BMI (p = 0.018) between 0 and 1 DRD2 risk allele copy. There is also a significant difference in ∆weight (p = 0.022), ∆BMI (p = 0.014), and %EWL (p = 0.032) among the different SNP expression values of the MAOA risk allele. In addition, Spearman’s correlation revealed that FCQ scores are negatively correlated with ∆BMI (r_s = −0.470, p < 0.05, 95% CI: −0.767, −0.005), %TWL (r_s = −0.561, p < 0.05, 95% CI: −0.814, −0.129), and %EWL (r_s = −0.533, p < 0.05, 95% CI: −0.800, −0.090) at 3 years post-surgery and positively correlated with 3-year weight (r_s = 0.576, p < 0.05, 95% CI: 0.151, 0.821) and 3-year BMI (r_s = 0.552, p < 0.05, 95% CI: 0.117, 0.810). Lastly, GARS scores are positively correlated with 3-year ∆weight (r_s = 0.422, p < 0.05, 95% CI: 0.010, 0.712).