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PubMed21 Apr 2026Diabetes care● 4/10i

Long-term Air Pollution and Overall and Regional Body Composition in Older Adults With Overweight or Obesity and Metabolic Syndrome.

Curto A, Konieczna J, Colom A, Abete I, de Hoogh K et al.

Long-term air pollution exposure was associated with higher body fat percentage and lower lean mass in older adults with overweight or obesity and metabolic syndrome over 3 years. Observational analysis of 1,454 Spanish adults from the PREDIMED-Plus trial, with DXA scans at baseline, 1 year, and 3 years. This provides the first longitudinal evidence that environmental factors may worsen body composition in metabolically vulnerable populations, potentially influencing treatment response in obesity and diabetes trials. Air pollution exposure was assigned at 100-meter resolution based on residential addresses, limiting generalizability to other geographic regions.

Strategic Signal

This environmental confounding factor could explain heterogeneous responses in obesity and diabetes trials across urban versus rural sites. Pharmaceutical companies running global trials should consider air pollution exposure as a stratification factor, particularly for metabolic endpoints in older populations. The finding may support regulatory submissions that include environmental exposure data to strengthen efficacy claims in real-world settings.

Weight lossType 2 diabetesReal-world evidence

Original Abstract

OBJECTIVE: To examine the relationship between long-term air pollution exposure, including black carbon (BC), fine particulate matter (PM2.5), and nitrogen dioxide (NO2), and total fat mass, visceral fat mass, and lean mass in older adults with overweight or obesity and metabolic syndrome. RESEARCH DESIGN AND METHODS: We included 1,454 older adults (aged 54-75 years; 48% female) from the PREDIMED-Plus trial in Spain who underwent baseline DXA scans at recruitment (2013-2016) and at 1- and 3-year follow-up. Annual air pollution exposure was assigned at participants' baseline residential address at 100 m resolution. We used linear mixed-effect regression models with interaction terms for exposure and time to examine longitudinal associations with body composition, also stratifying by sex, age, and physical activity. RESULTS: At baseline, a 1× 10-5/m increase in BC was associated with 1.01% (95% CI 0.31-1.71) higher body fat percentage, -0.97% (95% CI -1.64 to -0.30) lower lean mass percentage, and -0.74 kg (95% CI -1.37 to -0.12) lower lean mass. PM2.5 and NO2 showed similar relationships with body fat and lean mass percentage at baseline. These associations persisted in years 1 and 3 for BC and PM2.5. In age-stratified analyses, associations with visceral fat mass were observed only in participants younger than 65 years. Associations did not meaningfully differ by sex or physical activity. CONCLUSIONS: Long-term air pollution exposure was adversely associated with body composition over 3 years. Results indicate air pollution is associated with fat accumulation and lean mass loss in metabolically vulnerable older adults.

Related signals

Strategic Signal

FDA1 Apr 2026New Drug Approval (NDA/BLA)High impact● 10/10i

FDA Approves Foundayo (Orforglipron) — New Drug Approval (NDA/BLA)

FDA approved orforglipron (Foundayo, Eli Lilly) for type 2 diabetes -- a once-daily oral small-molecule GLP-1 receptor agonist. Orforglipron is the first non-peptide oral GLP-1 approved in the US; oral semaglutide (Rybelsus, Novo Nordisk) has been approved for T2D since 2019 and expanded to obesity in January 2026. Unlike Rybelsus, orforglipron requires no fasting or water volume restrictions before dosing.

GLP-1Type 2 diabetesPricing/accessEli LillyNovo Nordisk

Strategic Signal

Clinical Trial19 Mar 2026Phase 3High impact● 9/10i

Efficacy and Safety of Tirzepatide Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight-Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-1)

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Weight lossGLP-1Eli Lilly

Strategic Signal

FDA19 Mar 2026Supplemental Approval: Efficacy [Priority Review]High impact● 9/10i

FDA Approves Imcivree (Setmelanotide): Supplemental Approval: Efficacy [Priority Review]

FDA approved a supplemental application for Imcivree (setmelanotide, Rhythm) on March 19, 2026, under priority review. This represents an efficacy-based label expansion for the melanocortin-4 receptor agonist, which was initially approved for rare genetic obesity disorders. Rhythm gains additional indication breadth in the specialized rare obesity market, where treatment options remain extremely limited. The priority review designation signals FDA recognition of significant unmet medical need in the expanded patient population.

Weight lossOtherRhythm

Strategic Signal

Clinical Trial17 Apr 2026Phase 3High impact● 8/10i

A Phase 3, Open-Label Study of Once Daily LY3502970 Compared With Insulin Glargine in Adult Participants With Type 2 Diabetes and Obesity or Overweight at Increased Cardiovascular Risk

Phase 3 open-label trial compared once-daily oral orforglipron versus insulin glargine in people with type 2 diabetes and obesity or overweight at increased cardiovascular risk. The study enrolled 2,749 participants with primary endpoint of time to first major adverse cardiovascular event, completed in March 2026. Eli Lilly is positioning orforglipron as a cardiovascular outcomes option in high-risk populations, directly competing with established insulin therapy in this indication. This represents the first cardiovascular outcomes trial for orforglipron following its April 2026 FDA approval for type 2 diabetes.

GLP-1Type 2 diabetesWeight lossCardiovascularEli Lilly

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