PEG-loxenatide, a weekly GLP-1 receptor agonist, produced modest weight loss of 1.2 kg over 24 weeks in 68 type 2 diabetes patients, with effects varying by baseline BMI. Obese patients (BMI >28) achieved ≥5% weight loss 53% of the time, compared to just 28% in normal-weight individuals (BMI <24), alongside meaningful HbA1c reduction of 1.48%. This BMI-dependent response pattern represents a significant safety advantage over existing GLP-1 medications like semaglutide, which often cause excessive weight loss in already lean individuals. The finding addresses a critical gap in diabetes management, where normal-weight patients with type 2 diabetes need glycemic control without risking underweight status. While SGLT2 inhibitors showed slightly greater overall weight loss (2.4 kg), PEG-loxenatide's more conservative profile in lean patients could make it preferable for the substantial portion of Asian diabetes patients who aren't overweight. However, this single-center retrospective study of 136 matched patients represents preliminary evidence. The mechanism underlying this BMI-responsiveness remains unclear, and larger prospective trials are needed to confirm whether this represents a true therapeutic advantage or simply reflects the drug's overall modest potency compared to newer GLP-1 formulations.