Long‐term safety and efficacy of glucagon‐like peptide‐1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study

Aug 22, 2024Diabetes, obesity & metabolism

Long-term safety and benefits of weight-loss drugs in people with obesity but no type 2 diabetes

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Abstract

GLP-1 receptor agonist treatment was associated with a 23% lower risk of all-cause mortality.

Individuals treated with GLP-1 receptor agonists experienced a significant reduction in the risk of cardiovascular complications, including ischaemic heart disease and heart failure.
There was a lower incidence of arrhythmias, hypertension, stroke, and atrial fibrillation in those receiving GLP-1 receptor agonists.
GLP-1 receptor agonists were linked to a decreased risk of acute kidney injury and allergic reactions.
The observed protective effects were consistent across various subgroups and regions.

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AIM: We aimed to investigate the long-term impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D).

MATERIALS AND METHODS: In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP-1 RA treatment and those who did not receive glucose-lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event.

RESULTS: After propensity score matching, the study included 12,123 individuals in each group. GLP-1 RA treatment was associated with a significantly lower risk of all-cause mortality (hazard ratio 0.23; 95% confidence interval 0.15-0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP-1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions.

CONCLUSIONS: In this large observational study, GLP-1 RAs showed long-term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP-1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population.

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Long‐term safety and efficacy of glucagon‐like peptide‐1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study

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