Many patients with type 2 diabetes mellitus (T2DM) remain inadequately controlled despite treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Findings presented at the ADA Scientific Sessions 2026 evaluated whether icovamenib, an investigational oral menin inhibitor, could provide additional glycemic benefit in patients receiving background GLP-1 RA therapy.

This subgroup analysis was conducted within the randomized, placebo-controlled COVALENT-111 trial. Adults with T2DM and glycated hemoglobin (HbA1c) levels of 7.0% to 10.5% while receiving stable antihyperglycemic therapy were randomized to once-daily icovamenib 100 mg or placebo for 8 to 12 weeks while continuing baseline treatment. The current analysis included participants receiving GLP-1 RA therapy at baseline and assessed glycemic outcomes through week 52.

Findings

• The analysis included 12 participants treated with icovamenib and 4 treated with placebo.
• Baseline HbA1c was 8.4% in the icovamenib group and 7.9% in the placebo group.
• At week 52, mean HbA1c changed by −1.2% with icovamenib and +0.6% with placebo.
• Icovamenib achieved a placebo-adjusted HbA1c reduction of 1.8% (P=0.05).
• C-peptide index improved with icovamenib relative to placebo.
• No serious adverse events, treatment discontinuations, or new safety findings were reported, and the safety profile was consistent with the overall study population.

This subgroup analysis showed sustained HbA1c reductions with icovamenib in adults with T2DM receiving background GLP-1 RA therapy. The findings support further evaluation of menin inhibition as an adjunctive treatment approach for patients requiring additional glycemic control.