Semaglutide and tirzepatide represent new treatment modalities for type 2 diabetes mellitus (T2DM) and obesity, expanding the range of glucagon-like peptide-1 (GLP-1) receptor agonists. Semaglutide is a GLP-1 receptor analog while tirzepatide is a dual agonist that targets both glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors. Both are effective and well-tolerated treatments for managing T2DM and obesity, but their safety and effectiveness may vary across racial and ethnic groups. South Asians and Black individuals experience disproportionately higher rates of both obesity and diabetes compared to other racial and ethnic groups. These health disparities, along with socioeconomic barriers, highlight the urgent need for research to explore how semaglutide and tirzepatide perform across diverse populations. Asian populations, such as Japanese patients, appear to experience higher rates of gastrointestinal side effects with GLP-1 receptor agonists like semaglutide and tirzepatide compared to other groups. Additionally, South Asian adults who are older and have a lower BMI are more likely to discontinue the medication due to the heightened impact of side effects, particularly weight loss. Furthermore, Black populations also experience significant cardiovascular benefits with GLP-1 analogs, although the differences are less pronounced than in Asians. To ensure the best results, treatment plans should be tailored to the specific needs of individual patients, considering their ethnic backgrounds and socio-economic conditions, among other factors. This can be reinforced by improving patient education, offering support programs, and implementing policy changes to enhance medication adherence across diverse populations. Further research is needed to understand better how these factors vary across different populations and to optimize treatment strategies accordingly.