Management of type 2 diabetes mellitus (T2DM) needs to address hyperglucagonemic states, too, along with the insulin centric approach. Incretin physiology needs utmost attention as in type 2 diabetes incretins level declines like beta-cell function. Professor Robert Unger and his team had re-emphasized the importance of glucagon as the central pathogenic hormone in diabetes, which is responsible for accelerated catabolic destructions in the absence of insulin. Glucagon-like peptide 1 (GLP-1) analogs and dipeptidyl peptidase 4 (DPP4) inhibitors have the greatest potential to reduce the ill-effects of glucagon and metformin, and α-glucosidase inhibitors produce some effect to increase endogenous GLP-1 level and can address hyperglucagonemia. Using GLP-1 analog could be helpful to address misbalanced incretins axis in diabetics. Different professional societies of diabetes are now recommending GLP-1 receptor agonist (GLP-1 RA) like liraglutide, semaglutide, and dulaglutide in a variety of subgroups like people with atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, patient needing weight loss, or having high risk of hypoglycemia. Though exenatide had not shown beneficial role in cardiovascular outcome trial, it was proved to be safe in high risk cardiovascular patients. As Indian patients are more prone to develop incretin deficiency compare to the Caucasians, if we have more generic exenatide (in the 2017 patent expired), it may address this issue holistically. Past history of pancreatitis and family history of medullary thyroid carcinoma are two important serious concerns while using any GLP-1 RA. Informed prescribing on gastrointestinal side effects, such as nausea, anorexia, vomiting, and loose motion, needs to be addressed, and patients should be educated regarding mitigation strategies for these adverse effects.