If substantial weight reduction is desired or stroke prevention is prioritized, prefer a GLP-1 RA (79, 80). If heart failure (HF), chronic kidney disease (CKD), or reduction of HF hospitalization risk is a concern, prefer an SGLT2i (81). Combination therapy (GLP-1 RA + SGLT2i) may have synergistic/additive effects and further enhance cardio-renal protection (82, 83). This evidence concerns the gene GCG and hydrops fetalis.