Long-acting incretin therapies may help reduce treatment burden while maintaining glycemic control in patients with T2DM. Findings presented at the ADA Scientific Sessions 2026 evaluated the efficacy and safety of PG-102, a bispecific Fc fusion protein targeting glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) receptors, administered every two weeks or every four weeks in adults with T2DM.

This randomized, double-blind, placebo-controlled Phase 2a study evaluated PG-102 in adults with type 2 diabetes mellitus (T2DM) receiving stable metformin with or without one oral antidiabetic medication. Eligible participants had glycated hemoglobin (HbA1c) levels of 7.0%-10.0% and body mass index (BMI) between 18.5 and 30 kg/m².

Participants were randomized to PG-102 60 mg every two weeks (Q2W), every four weeks (Q4W), or placebo. The primary endpoint was change in HbA1c at week 14, while secondary endpoints included fasting plasma glucose (FPG) and treatment-emergent adverse events. Exploratory analyses evaluated changes in body weight and body composition. A total of 48 adults with T2DM were enrolled, with a mean age of 61.9 years and mean diabetes duration of 12.5 years.

Findings

• Approximately 88% of participants were receiving two oral antidiabetic drugs at baseline.
• At week 14, placebo-adjusted least-squares mean HbA1c reductions were −1.41% (95% CI −1.94 to −0.87; P<0.0001) with Q2W dosing and −0.87% (95% CI −1.30 to −0.45; P=0.0003) with Q4W dosing.
• Mean FPG reductions were −34.4 mg/dL and −29.9 mg/dL with Q2W and Q4W dosing, respectively, compared with reductions of −11.3 mg/dL and −7.5 mg/dL with placebo.
• Gastrointestinal adverse events occurred at rates comparable to placebo, and no gastrointestinal adverse drug reactions were reported in the Q4W group.
• Exploratory analyses showed 7.10%-9.87% fat mass reduction with <1% lean mass change in the Q2W group and a 1.10% lean mass increase in the Q4W group. 

This Phase 2a study showed that PG-102 improved glycemic control with both biweekly and monthly dosing schedules in adults with T2DM. The findings also suggested favorable gastrointestinal tolerability and body composition changes, supporting further clinical evaluation of long-acting GLP-1/GLP-2 receptor-targeted therapy.