Complementary body weight and cardiometabolic benefits of higher GLP-1 and lower GIP: Genetic evidence from…

Cohort studyMetabolism: clinical and experimental· Jul 2026

Complementary body weight and cardiometabolic benefits of higher GLP-1 and lower GIP: Genetic evidence from large-scale phenomic analyses.

Lijuan Wang, Fangyuan Jiang, Shuai Yuan … Christos S Mantzoros

Venous ThromboembolismCohort studyQ1IF 15.7

Genetically higher GLP-1 plus lower GIP levels linked to lower obesity risk

Complementary body weight and cardiometabolic benefits of higher GLP-1 and lower GIP: Genetic evidence from large-scale phenomic analyses.

Lijuan Wang … Christos S Mantzoros

Metabolism: clinical and experimental · Jul 2026

Background

The long-term health effects of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) remain unclear.

Methods

TreeWAS was first conducted to map associations of GLP-1 or GIP levels with a broad range of disease outcomes among 385,917 UK Biobank participants.

Results

genetics tied to more GLP-1 and less GIP lowered obesity risk

HR by subgroup · 95% CI

More results

TreeWAS analysis revealed associations of elevated genetically predicted GLP-1 levels, even within the normal range, with decreased risk of metabolic diseases (e.g. type 2 diabetes) and polyarthropathies (e.g. gout).

More results

While genetically determined low GIP levels were linked to reduced risk of obesity, metabolic diseases (e.g. disorders of lipoprotein metabolism and other lipidaemias), digestive/hepatic and cardiometabolic diseases.

“

Conclusion

Our genetic findings are consistent with the hypothesis that GLP-1 levels in the higher physiological range and GIP levels in the lower physiological range, individually and jointly, may be associated with lower body weight and improved cardiometabolic and liver phenotypes, while these observations warrant mechanistic and clinical investigation.

Complementary body weight and cardiometabolic benefits of higher GLP-1 and lower GIP: Genetic evidence from large-scale phenomic analyses.

Complementary body weight and cardiometabolic benefits of higher GLP-1 and lower GIP: Genetic evidence from large-scale phenomic analyses.

Related papers