Conclusion
Suggest Approach for Minimizing Hypoglycemia
Given the current state of knowledge, we propose that avoidance of hypoglycemic events is an important consideration in choosing a therapeutic regimen in individuals with T2DM. Metformin constitutes the first line of therapy, and its use is rarely associated with hypoglycemic events. The addition of a DPP-4 inhibitor, GLP-1 RA, or perhaps a TZD to metformin should be given primacy if hypoglycemia is a significant concern in a particular patient (Fig. 3); the long-term safety of DPP-4 inhibitors and GLP-1 RAs is still under investigation. Meglitinides or SUs can be employed as a second agent, with the understanding that their use is associated with low to moderate rates of hypoglycemia. One can also initiate insulin therapy as a second agent. Among the various approaches for insulin use, treatment with basal insulin, especially an analog insulin, is associated with fewer hypoglycemic events. It is hoped that newer analog insulins, such as insulin degludec, will further minimize this risk due to their more physiologic nature. As further escalation of insulin therapy is needed, addition of a DPP-4 inhibitor or a GLP-1 RA instead of prandial insulin to the regimen can be considered; use of the former alternatives is associated with fewer hypoglycemic events. In order to ensure optimal patient outcomes, the need for avoidance of hypoglycemia and knowledge of unwanted effects of various pharmacologic agents on producing hypoglycemia should be communicated to the entire diabetes-management team.