SAT-708 - Body Weight Reduction with Orforglipron by Obesity Duration in Adults with Obesity: Post Hoc Analyses of ATTAIN-1 and ATTAIN-2

Introduction: Orforglipron (OFG), an oral non-peptide glucagon-like peptide-1 receptor agonist, resulted in significant weight reduction in participants with obesity, with and without type 2 diabetes, in the ATTAIN-1 (NCT05869903) and ATTAIN-2 (NCT05872620) clinical trials. This post hoc analysis examined the association between participants’ duration of obesity and weight reduction with OFG.

Methods: We analyzed data from the phase 3 ATTAIN-1 and ATTAIN-2 clinical trials, which examined efficacy and safety of 6, 12, or 36 mg daily dosing of OFG versus placebo as an adjunct to healthy diet and physical activity, in adults with overweight or obesity, without (ATTAIN-1) or with (ATTAIN-2) type 2 diabetes. Obesity duration subgroups (≤10 years, >10 to ≤20 years, or >20 years at baseline) were defined using self-reported data. Percent change in body weight from baseline to week 72 was analyzed using a mixed model for repeated measures guided by the efficacy estimand. Trend tests of treatment effects across obesity duration categories were conducted using a Chi-square test based on inferential results from models.

Results: There were 2869 participants in ATTAIN-1 (obesity duration: ≤10 years, n=1351; >10 to ≤20 years, n=808; >20 years, n=710) and 1270 in ATTAIN-2 (n=392, n=363, and n=515 in each category, respectively). In both trials, placebo corrected mean reductions in body weight (%) were significant for all doses within each obesity duration subgroup (p < 0.001), with greater weight reductions consistently found at higher OFG doses. At 36 mg OFG, placebo-corrected mean weight reductions from baseline showed little variation across subgroups of increasing obesity duration (ATTAIN-1: −11.5% [95% confidence interval (CI) −12.8 to −10.1%], −11.3% [95% CI −12.9 to −9.6%], −10.9% [95% CI −12.8 to −9.1%]; ATTAIN-2: −8.5% [95% CI −10.6 to −6.4%], −8.0% [95% CI −9.9 to −6.1%], −9.2% [95% CI −11.1 to −7.3%]). There was also little variation in weight reduction by obesity duration subgroup at 6 mg and 12 mg doses in both ATTAIN-1 and ATTAIN-2. Trend tests indicated that weight reduction was not significantly associated with obesity duration category for any dose in either trial (all p-values >0.05).

Conclusions: In this post-hoc analysis of ATTAIN-1 and ATTAIN-2, OFG treatment in adults with overweight and obesity demonstrated significant body weight reductions compared with placebo regardless of the duration of obesity, supporting its efficacy across the spectrum of disease duration.

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