Emerging glucagon-based therapies in diabetes mellitus: Toward a better future in diabetes care

Diabesity and the related complications are challenging problems in the current era. Conventionally, glucagon was known for its benefit in the management of hypoglycemia due to its involvement in the counter-regulatory mechanism. The studies in the last decade have brought a tremendous change in the therapeutic benefits of glucagon, due to the identification of multiple pleiotropic effects of it. This has resulted in the development of newer therapies for diabetes and obesity by the incorporation of glucagon agonism into incretin-based therapies. These novel dual/triple agonists containing glucagon and incretins give promising and synergistic advantages in the management of metabolic complications of diabesity. The metabolic effects of glucagon receptor antagonists have been disappointing. In addition, novel stable formulations have been developed for the management of hypoglycemia. Dual-hormone automated delivery systems containing insulin and glucagon are another attractive advancement on the process of development to minimize hypoglycemia in long-standing diabetes parallelly with improvement in glycemic control. We summarize the novel mechanisms of glucagon identified and the glucagon-based advancements in the management of diabetes mellitus.