Diabetes mellitus (DM) is recognized as the most common and the world’s fastest-growing
chronic disease with severe complications leading to increased mortality. Many strategies exist for the
management of DM and its control, including treatment with insulin and insulin analogs, oral hypoglycemic
therapy such as insulin secretion stimulators and insulin sensitizers, and diet and physical training.
Over the years, many types of drugs and molecules with an interesting pharmacological diversity
have been developed and proposed for their anti-diabetic potential. Such molecules target diverse key
receptors, enzymes, and regulatory/signaling proteins known to be directly or indirectly involved in the
pathophysiology of DM. Among them, insulin receptor (IR) is undoubtedly the target of choice for its
central role in insulin-mediated glucose homeostasis and its utilization by the major insulin-sensitive tissues
such as skeletal muscles, adipose tissue, and the liver. In this review, we focus on the implication
of antibodies targeting IR in the pathology of DM as well as the recent advances in the development of
IR antibodies as promising anti-diabetic drugs. The challenge still entails development of more powerful,
highly selective, and safer anti-diabetic drugs.