Enigma protein, encoded by the PDLIM7 gene, is overexpressed in thyroid cancer in a stage-dependent manner, suggesting a potential involvement in the initiation and progression of thyroid cancer. The Enigma interacts with several cellular pathways, including PI3K/AKT, MDM2, and BMP-1. The Enigma is regulated by microRNAs. Specifically, we showed that the Enigma protein upregulation corresponds to the downregulation of Let-7 family genes. There is limited research on the interactions and regulation of the Enigma with other proteins/genes in thyroid cancer tissues, indicating a gap in current knowledge. Our aim is to establish the Enigma as a biomarker. We also aim to study the interacting partners of the Enigma signaling pathways and their probable miRNA regulation in thyroid cancer progression. Using Western blotting, densitometric analysis, immunoprecipitation (IP), and reverse IP, we detected the protein expression and protein–protein interactions in the corresponding papillary thyroid carcinomas (PTCs). Utilizing real-time qPCR assay and Pearson’s correlation test, we highlighted the correlation between PDLIM7 and Let-7g gene expression in the same tissues. The results showed the differential upregulations of the Enigma protein in different stages of PTCs compared to benign tissues along with AKT, VDR, BMP-1, and MDM2 proteins. Loss of DBP was observed in a subset of PTCs. Strong interactions of the Enigma with PI3K/AKT and MDM2 were noted, along with a weaker BMP-1 interaction. Pearson’s correlation coefficient analysis between PDLIM7 and let-7g gene expression was significant (p < 0.05); however, there was a weak inverse correlation (r = −0.27). The study suggests the potential utility of the PDLIM7-qPCR assay as a biomarker for thyroid cancer. The Enigma’s interactions with key signaling pathways may provide valuable insights into the development of thyroid cancer. The study contributes to understanding the molecular mechanisms involving the Enigma protein in thyroid cancer and highlights its potential as a biomarker.

Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is widely prescribed for type 2 diabetes and obesity. Rodent studies showed thyroid C-cell tumors, prompting a boxed warning for medullary thyroid carcinoma (MTC); whether this extends to papillary thyroid carcinoma (PTC), a follicular-cell-derived tumor, is uncertain. This narrative review examines semaglutide and other GLP-1RAs in relation to PTC, distinguishing semaglutide-specific from class-level evidence, and PTC from differentiated thyroid cancer (DTC), MTC, and thyroid cancer overall. Most human studies evaluated GLP-1RAs as a class and reported thyroid cancer overall; semaglutide-specific and PTC-specific estimates are scarce. Pooled trials and national cohorts mostly showed no statistically significant increase in thyroid cancer, although three separate meta-analyses of randomized trials each reported a statistically significant increase in overall thyroid cancer, and case-control and spontaneous-reporting studies reported signals vulnerable to detection bias and confounding. In a matched cohort of 1072 patients with DTC, GLP-1RA exposure (median 16 months) was not significantly associated with progression over 69 months. Receptor-expression findings were inconsistent, and preclinical data did not show proliferative effects. The cohort and progression findings indicate no statistically detectable increase within the available sample sizes, exposure durations, and event numbers; they do not establish oncological safety. Semaglutide-specific, histology-resolved studies with longer exposure are needed.

Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) marketed as Ozempic and Wegovy, is now among the most widely prescribed medications for type 2 diabetes and obesity. Rodent carcinogenicity studies demonstrated dose- and duration-dependent thyroid C-cell tumors, prompting a boxed warning for medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia type 2 (MEN2), but whether this concern extends to papillary thyroid carcinoma (PTC), a follicular-cell-derived malignancy with distinct biology, remains uncertain. This narrative review evaluates current evidence on semaglutide and PTC, examining incidence, progression in patients with existing disease, receptor expression and mechanistic data, pharmacovigilance signals, sex-based patterns, and case reports published through August 2026. A pooled analysis of 93 trials (101,732 participants) and several national cohort studies found no statistically significant increase in thyroid cancer risk, and a matched cohort of 1072 patients with existing differentiated thyroid cancer found no association between GLP-1RA exposure and structural progression over a median of 69 months. A French case-control study and two FAERS disproportionality analyses reported elevated risk signals subject to detection bias and confounding by obesity. Receptor expression and functional studies were inconsistent but did not generally support a proliferative effect of GLP-1R agonism on PTC cells. Taken together, current evidence does not support semaglutide as a driver of PTC incidence or progression, though this remains an area warranting further prospective, subtype-specific study.

Obesity is a chronic, relapsing disease associated with significant morbidity, mortality, and rising healthcare costs. It represents one of the most urgent global health challenges of the 21st century. With the continued surge of obesity among children and adolescents, the burden in adulthood is projected to escalate further, fueling an epidemic of non-communicable diseases (NCDs) such as type 2 diabetes, cardiovascular disease, and cancer. Once regarded as a problem confined to Western nations, obesity is now rising sharply across the globe, including in South Asia and Bangladesh, where it threatens to derail public health progress. Advances in our understanding of weight regulation and the gut–brain axis have paved the way for a new generation of safe and effective pharmacotherapies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide 2.4 mg once weekly, approved in 2021, deliver unprecedented results, achieving an average weight reduction of 15–17% by targeting appetite and satiety pathways. The dual incretin agent tirzepatide (GLP-1/GIP RA) has further expanded therapeutic possibilities, initially approved for type 2 diabetes and now established as an option for obesity care. Additional entero-pancreatic and non-entero-pancreatic hormone-based agents are under active investigation. This emerging therapeutic landscape signals a paradigm shift: obesity management is shifting toward individualized treatment strategies, similar to those used in diabetes or dyslipidemia care. Treatment selection could be tailored not only to weight reduction goals but also to obesity-related complications. Ectopic fat accumulation drives organ-specific dysfunctions—including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD)/ metabolic dysfunction-associated steatohepatitis (MASH), and heart failure with preserved ejection fraction (HFpEF). Some agents, such as GLP-1/glucagon combinations, demonstrate weight-independent effects on liver fat reduction, suggesting opportunities for tailored therapy. Moreover, robust cardiovascular and renal outcome data are already available for several newer anti-obesity agents, reinforcing their potential to improve survival as well as quality of life. The new era of obesity care is therefore defined not merely by greater weight loss, but by improved, patient-centered outcomes across metabolic, cardiovascular, hepatic, and renal domains. The challenge for clinicians is to translate this evidence into practice—ensuring equitable access, long-term adherence, and individualized therapeutic decisions to reduce the global burden of obesity and its complications. [J Assoc Clin Endocrinol Diabetol Bangladesh, 2025;4(Suppl 1): S30]