GCG and obesity due to melanocortin 4 receptor deficiency: Notably, the GLP-1-estrogen conjugate, which is designed to activate estrogen receptors in GLP-1 targeted tissues, has superior efficiency over either of the individual hormones to overcome obesity, hyperglycemia, and dyslipidemia while at the same time prevents hallmark side effects of estrogen such as reproductive toxicity and oncogenicity (109).