Genetic disparities in GLP-1 obesity drug efficacy reveal systemic inequities in precision medicine and metabolic health research

Indigenous and traditional medicine systems have long addressed metabolic health through land-based, holistic frameworks that integrate diet, spirituality, and community well-being, yet these are systematically excluded from genomic research agendas. The study’s focus on GLP-1 drugs—a Western pharmaceutical solution—ignores the efficacy of Indigenous practices like intermittent fasting (e.g., *Ramadan* in Islam, *Hindu* *Ekadashi* vows) or fermented foods (e.g., *kimchi*, *dosa*) in regulating metabolism. Colonial histories of suppressing Indigenous knowledge (e.g., the banning of Native American plant-based medicines) continue to shape which health solutions are deemed 'scientific.'

The genetic determinism framing echoes eugenics-era pseudoscience, where body size and health were racialized to justify discrimination (e.g., 19th-century 'scientific racism' linking obesity to 'degeneracy'). The study’s reliance on BMI—a metric invented by a statistician (Adolphe Quetelet) and later weaponized by insurers and colonial regimes—perpetuates these harms. Historical parallels include the Tuskegee experiments and Henrietta Lacks’ cells, where marginalized bodies were commodified for biomedical gain without consent or benefit-sharing.

Cross-cultural comparisons reveal that metabolic health is often framed as a collective, not individual, responsibility—whether in the African concept of *Ubuntu* ('I am because we are') or the Japanese *Shokuiku* (food education) policies that prioritize school gardens and communal meals. In Latin America, the *Dieta Tradicional Mexicana* (rich in beans, maize, and chiles) has been shown to reduce obesity rates compared to Western diets, yet such diets are marginalized in genomic studies. The study’s Eurocentric cohort (28,000 predominantly European participants) contrasts with global obesity trends, where 60% of affected individuals live in low- and middle-income countries.

The study’s methodology—using GWAS to identify genetic variants linked to GLP-1 side effects—is robust but constrained by its narrow participant pool and reliance on BMI as a health metric. GWAS studies have repeatedly shown that genetic contributions to obesity are polygenic and context-dependent, yet the paper frames efficacy as a binary 'works or doesn’t work' rather than a spectrum influenced by environment. The focus on gastrointestinal side effects overlooks broader metabolic outcomes (e.g., muscle loss, micronutrient deficiencies) that are critical for long-term health. The lack of diversity in genomic databases (e.g., <2% of GWAS participants are of African ancestry) undermines the generalizability of findings.

Artistic and spiritual traditions often depict obesity as a metaphor for imbalance—whether in Buddhist teachings on craving (*tanha*), the Hindu concept of *Maya* (illusion of material excess), or the African diasporic practice of *diasporic cooking* that transforms colonial foods into healing meals. The GLP-1 drug narrative reflects a mechanistic, reductionist worldview that contrasts with Indigenous storytelling, where health is a relational process (e.g., the Māori *whakapapa* connection to land and food). Western art, however, has long critiqued this paradigm, from Frida Kahlo’s self-portraits of bodily pain to Kara Walker’s explorations of racialized consumption.

Future scenarios must account for the intersection of genetic research, climate change, and food systems—e.g., how rising temperatures may alter drug metabolism or how soil depletion (linked to industrial agriculture) reduces nutrient density in food. The current model risks creating a 'genetic underclass' where marginalized groups face higher side effects due to lack of representation in trials, while wealthy nations benefit from personalized medicine. Alternative models could prioritize community-led genomic databases (e.g., *All of Us* but with Indigenous governance) or policy interventions like taxing ultra-processed foods to fund diverse clinical trials.

Marginalized communities—particularly Black, Indigenous, and low-income populations—are disproportionately excluded from obesity drug trials, yet they experience the highest rates of obesity-related comorbidities due to structural inequities like food apartheid and environmental racism. The study’s focus on gastrointestinal side effects ignores how these communities already face higher risks of medical mistrust due to histories of abuse in research (e.g., the *Pfizer meningitis trial* in Nigeria). Solutions must center these voices, such as participatory research designs where communities co-define research questions and benefit-sharing mechanisms.