Sustained Versus Minimal GLP-1 Receptor Agonist Exposure and Metabolic Outcomes in Older Adults Without Diabetes.

AIMS: To compare changes in body mass index (BMI) categories after sustained versus minimal glucagon-like peptide-1 receptor agonist (GLP-1 RA) exposure in older adults with obesity and without diabetes. A secondary aim was to compare changes in glycated haemoglobin (HbA1c) categories among those with paired HbA1c measurements.

MATERIALS AND

METHODS

Retrospective cohort study within Clalit Health Services, Israel. Adults aged ≥ 65 years without diabetes, with baseline BMI ≥ 30 kg/m2 and paired BMI measurements, were classified as minimal (1-2 dispensations) or sustained (≥ 3) exposure. The primary outcome was BMI category improvement. Secondary outcomes were relative BMI change, HbA1c category change in the paired-HbA1c subset, and incident diagnosed diabetes. BMI improvement was modelled by logistic regression adjusted for age, sex, socioeconomic status and comorbidity.

RESULTS

Of 13 387 patients (69% female), 11 121 (83%) had sustained and 2266 (17%) minimal exposure. BMI category improved in 55% of the sustained versus 30% of the minimal group (p < 0.001; median change -8% vs. -2%). Among 7392 with paired HbA1c, HbA1c improved in 34% versus 20% (sustained vs. minimal; p < 0.001), and 65% versus 37% of those with prediabetes became normoglycaemic. Diabetes diagnosis was less frequent with sustained exposure (2.5% vs. 5.3%; p < 0.001). Adjusted for measured confounders, sustained exposure was associated with BMI improvement (OR: 2.77, 95% CI: 2.51-3.06).

CONCLUSIONS

Among older adults with obesity and without diabetes, sustained versus minimal GLP-1 RA exposure was associated with greater improvement in BMI and HbA1c categories and a lower incidence of diabetes. These findings describe observed changes after treatment initiation, not a proven causal treatment effect.