Novel glucagon-like peptide-1 (GLP-1) receptor agonists continue to expand therapeutic options for type 2 diabetes mellitus (T2DM), with tolerability remaining an important consideration during dose escalation. Findings presented at the ADA Scientific Sessions 2026 reported interim efficacy and safety data for GL0034, a once-weekly GLP-1 receptor agonist, in adults with T2DM receiving metformin with or without a sodium-glucose cotransporter-2 (SGLT2) inhibitor.

This double-blind, placebo-controlled study randomized participants to GL0034 administered once weekly using two different dose-escalation regimens or placebo over 16 weeks. Gastrointestinal adverse events (GI AEs) were assessed using a symptom score. Efficacy endpoints included body weight, glycated hemoglobin (HbA1c), mean daily self-monitored plasma glucose (SMPG), peak glucose concentration after a liquid meal test, and waist circumference.

Findings

• GL0034 was generally well tolerated across both dose-escalation regimens.
• Gastrointestinal adverse event rates were similar between treatment cohorts, although symptom scores were numerically higher in cohort 1.
• The incidence of treatment-emergent adverse events was comparable between the two GL0034 cohorts.
• Over 16 weeks, GL0034 reduced body weight and improved glycemic parameters compared with placebo.
• Improvements were observed in HbA1c, mean daily SMPG, peak glucose concentration following liquid meal testing, and waist circumference.
• Efficacy outcomes were not significantly different between the two GL0034 dose-escalation cohorts.

This interim analysis showed that GL0034 improved glycemic control and body weight with generally similar tolerability across two dose-escalation strategies in adults with T2DM. Longer-term studies are needed to further evaluate efficacy, gastrointestinal tolerability, and safety outcomes.