A 48 year old male is diagnosed with type 2 Diabetes Mellitus after presenting to the emergency room with symptoms of hyperglycemia. He was immediately started on insulin and has been very compliant with his regimen. His initial Hemoglobin A1C at the time of diagnosis was 15. However, over the past few months, due to hypoglycemia, his insulin dosage has been titrated down. He is currently on low doses of NPH and aspart, with an A1C of 6.6. Would it be possible to convert this patient to oral agents, and, if so, what is the best way to transition to an oral regimen?
Commentary by Terry Seltzer MD, Department of Endocrinology
Before deciding to convert the patient from insulin to an oral agent, one must first be certain that he is a Type 2 Diabetic. Thus the lean 20 year old patient should be considered a possible Type 1 Diabetic, even though thus far he phenotypically appears to be a Type 2. In such patients consider obtaining an anti-glutamic acid decarboxylase antibody (Anti-GAD Ab) – if positive this would strongly suggest Type 1 Diabetes and I would suggest continuing the patient on insulin.
Once we have established that the patient is a Type 2 Diabetic, one must weigh the risks and benefits of continuing the insulin versus a trial of an oral agent. Since the patient is already well controlled and presumably well adjusted to the insulin, any change is likely to at least temporarily disrupt his control. On the other hand, insulin is known to promote weight gain. Patients almost universally prefer oral agents to insulin because of its ease of administration, but also because they perceive their illness to be less serious when on oral agents. Certain oral agents also offer some additional benefits. Metformin was shown in the UKPDS study to reduce the risk of a myocardial infarction by about 40% over a five-year period in obese Type 2 Diabetics. The thiazoladinediones, pioglitazone and rosiglitazone, may prevent progressive islet cell burnout. In general, I would usually attempt to change the insulin to an oral agent after several weeks. One exception is the woman who is contemplating pregnancy in the near future – she should be continued on insulin.
Which oral agent to choose? First one must consider the patient’s comorbidities. Certain agents may be ruled out after such consideration. If the patient has renal insufficiency, metformin must not be used, and sulfonylureas carry a greater risk of hypoglycemia. In congestive heart failure and in chronic liver disease, both metformin and the thiazoladinediones are contraindicated. In the frail and/or elderly patient, it may be desirable to avoid the risk of hypoglycemia associated with the sulfonylureas and repaglinide.
In patients with the metabolic syndrome (abdominal obesity, hypertension, high LDL cholesterol, low HDL cholesterol, and high triglycerides associated with a severe insulin resistance), a trial of a thiazoladinedione addresses the underlying pathology most directly and might be considered the agent of choice. However, the recent meta-analysis suggesting a 43% higher incidence of myocardial infarctions in patients treated with rosiglitazone calls this into question. More data is needed to address this question.
For most other patients, I believe metformin is the first choice because of its beneficial effect on the risk of atherosclerotic heart disease and weight reduction. The usual starting dose of metformin is 500 mg before breakfast and dinner. In general, I try to avoid the sulfonylureas because of the risk of severe hypoglycemia, and its negative effect on beta cell survival. Whatever oral agent is chosen, the patient must be followed carefully when insulin is discontinued. Often, the patient will be instructed to use a sliding scale of a rapidly acting insulin temporarily until the effectiveness of the oral agent can be determinined. One reasonable sliding scale would be: 3 units for a glucose of 180 to 240, 5 units for 241 to 320, 8 units for 321 to 400, and 10 units for more than 400, but the dosage should be individualized for each patient. The patient and physician must be in frequent communication during this time.
Image of insulin molecule, courtesy of Wikimedia Commons.