Key inclusion and exclusion criteria for the ATTAIN-1 study are presented in Key Inclusion and Exclusion Criteria in ATTAIN-1.

The ATTAIN-1 trial randomized 3127 participants across the US, Brazil, China, India, Japan, South Korea, Puerto Rico, Slovakia, Spain, and Taiwan in 3:3:3:4 ratio to receive either 

• orforglipron 6 mg
• orforglipron 12 mg 
• orforglipron 36 mg, or 
• placebo.2

During the study, orforglipron was taken without food and water restrictions.1,3

The primary objective in ATTAIN-1 was to demonstrate that orforglipron (6 mg, 12 mg, 36 mg) is superior to placebo in percent change in body weight from baseline to week 72.2

In ATTAIN-1, all participants in the orforglipron treatment arms started the study at a dose of orforglipron 1 mg once-daily and then increased the dose in a step-wise approach at 4-week intervals to their final treatment dose of

• 6 mg (via steps at 1 mg and 3 mg)
• 12 mg (via steps at 1 mg, 3 mg, and 6 mg), or
• 36 mg (via steps at 1 mg, 3 mg, 6 mg,12 mg, and 24 mg).1

Dose reduction was only allowed for gastrointestinal (GI) tolerability if other mitigations failed.1

Two statistical estimands, efficacy or treatment-regimen, were used to evaluate efficacy data in ATTAIN-1.1

• The efficacy estimand represents efficacy had all randomized participants remained on study intervention (with possible dose interruptions and modifications) for 72 weeks without initiating prohibited weight management treatments.1
• The treatment-regimen estimand represents the estimated average treatment effect Regardless of adherence to study intervention or initiation of prohibited weight management treatments.1

In ATTAIN-1, treatment with orforglipron met the primary endpoint of superior body weight reduction compared to placebo.1

As described in Efficacy Endpoints from ATTAIN-1 (Efficacy Estimand), for the efficacy estimand, body weight was reduced from baseline to week 72 in a dose-dependent manner by 7.8% to 12.4% (17.6 lbs to 27.3 lbs) with orforglipron compared with 0.9% (2.2 lbs) with placebo.1

Key secondary endpoints for the efficacy estimand are presented in Efficacy Endpoints from ATTAIN-1 (Efficacy Estimand).

For the treatment-regimen estimand, each dose of orforglipron led to statistically significant improvements across primary and all key secondary endpoints. From baseline to week 72, the mean percent change in body weight was -7.5% to -11.2% (-17.2 lbs to -25.0 lbs) with orforglipron compared with -2.1% (-5.3 lbs) with placebo as described in Efficacy Endpoints from ATTAIN-1 (Treatment-Regimen Estimand) .1

Key secondary endpoints for the treatment-regimen estimand are described in Efficacy Endpoints from ATTAIN-1 (Treatment-Regimen Estimand) .

In addition to achieving significant weight loss, orforglipron was also associated with reductions in known markers of cardiovascular risk, including non-HDL cholesterol, triglycerides and systolic blood pressure in pooled analyses across all doses.1 

In a pre-specified exploratory analysis, treatment with orforglipron 36 mg  reduced high-sensitivity C-reactive protein (hsCRP) levels by 47.7%.1

The overall safety profile of orforglipron in ATTAIN-1 was consistent with the established GLP-1 receptor agonist class.1

The most commonly reported adverse events were GI-related and generally mild-to-moderate in severity. Most Common Adverse Events For Participants Treated with Orforglipron in in ATTAIN-1 presents the most common adverse events for participants treated with orforglipron.1

Treatment discontinuation rates due to adverse events were 5.1%, 7.7%, and 10.3% with orforglipron 6 mg, 12 mg, and 36 mg, respectively, compared with 2.6% with placebo.1

The overall treatment discontinuation rates were 21.9%, 22.5%, and 24.4% with orforglipron 6 mg, 12 mg, and 36 mg, respectively, compared with 29.9% with placebo.1

No hepatic safety signal was observed.1