Combined Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) and Sodium-Glucose Cotransporter 2 Inhibitor (SGLT2i) Therapy to Restore Fertility in Patients With Obesity, Polycystic Ovary Syndrome, and Incident Type 2 Diabetes

Obesity and type 2 diabetes (T2D) frequently complicate polycystic ovary syndrome (PCOS), exacerbating subfertility. We report two cases of obese women with newly diagnosed T2D and PCOS-related subfertility successfully treated with a combination of a glucagon-like peptide-1 receptor agonist (GLP-1RA) and a sodium-glucose co-transporter 2 inhibitor (SGLT2i). Both patients achieved rapid, substantial weight loss (23% and 10.2%, respectively), leading to menstrual normalization and accidental spontaneous conception within seven months. Medications were discontinued upon confirmation of pregnancy. Both pregnancies were uncomplicated, resulting in healthy live births. Early combination therapy with GLP-1RA and SGLT2i may offer a potent approach to expedite spontaneous conception in this high-risk population. While inadvertent early pregnancy exposure shows no major teratogenic concern based on emerging preliminary studies, immediate discontinuation with transitioning to metformin and/or insulin prior to planning pregnancy remains the clinical standard until robust safety profiles regarding embryotoxicity are established.