Analysis of 5.15 million adults with type 2 diabetes across ten international databases revealed significant sex differences in safety profiles for second-line diabetes medications, particularly GLP-1 receptor agonists. Women taking GLP-1 drugs showed 39% higher risk of acute pancreatitis compared to SGLT2 inhibitors, while men experienced no increased risk. Conversely, men had 13% lower hypotension risk with GLP-1 drugs, while women showed no difference. Drug prescription patterns also varied markedly by sex, with women receiving GLP-1 drugs nearly twice as often as men (9.28% vs 5.41%). These findings fill a critical knowledge gap given women's historical underrepresentation in diabetes clinical trials. The sex-specific safety profiles suggest personalized prescribing approaches may optimize outcomes, particularly relevant as GLP-1 drugs gain popularity for weight management beyond diabetes control. However, cardiovascular effectiveness showed no sex differences across all drug classes. The massive real-world dataset strengthens confidence in these patterns, though this preprint awaits peer review and results may change. This represents confirmatory evidence with important clinical implications for precision diabetes care.