What is the basis for selecting and adding a second agent to metformin in the treatment of type 2 diabetes mellitus (DM)?

Updated: Oct 23, 2019
  • Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
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Answer

Considerable debate exists regarding which second agent to add to (or use initially in conjunction with) metformin. An outline of the therapeutic approach generally used by the author is presented in the first 2 images below. An idealized scheme for glucose and insulin patterns is presented in the third image below. The author finds that keeping such an idealized scheme in mind is helpful when treating and educating patients, even if the patient is trying to replicate it with less intensive insulin therapy.

Treatment of type 2 diabetes mellitus. Treatment of type 2 diabetes mellitus.
Simplified scheme for using insulin in treating pa Simplified scheme for using insulin in treating patients with type 2 diabetes mellitus.
Simplified scheme of idealized blood glucose value Simplified scheme of idealized blood glucose values and multiple dose insulin therapy in type 2 diabetes mellitus.

Because TZDs not infrequently cause weight gain and edema, the author usually reserves these agents for patients who cannot use metformin, as a result of intolerance or contraindications. Exceptions to this practice may include patients of relatively normal weight who have marked insulin resistance, such as patients of Asian heritage.

Before adding a second agent for a patient who is taking an insulin secretagogue, the clinician should warn the patient about the possibility that the second agent will induce hypoglycemia. If hypoglycemia occurs, the dose of the insulin secretagogue, not the newly added agent, should be reduced.


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