Managing Between-meal Hypoglycemia 1
I would like to discuss this case of a patient who, overall, was doing well on her therapy until she made an important lifestyle change to lose weight. This is a common problem because, often, our patients make such lifestyle decisions and do not always tell us. They come to see us because they experience an adverse event, and we need to explore the reasons why specific problems might have occurred. In this case, Mathilda began to develop symptoms of hypoglycemia after losing a significant amount of weight. This posed a difficult problem in the management of her diabetes because her A1C was still not at goal. Let s take a look at how I decided to handle this case. 2
You suspect that her symptoms might be due to hypoglycemia so you give her a home blood glucose monitor and ask her to check the glucoses throughout the day. When she returns to the office the following week, the record reveals multiple episodes of hypoglycemia between meals, which correlate with her symptoms. 3
What are the key patient features in considerations for individualized therapy of this patient? What should her A1C target be? Why is she experiencing these episodes of hypoglycemia? She also has a desire to lose weight, which would lead to considerations for her treatment. She also has hypertension. Fortunately, her renal function is normal. 4
This slide illustrates the ADA/EASD General Recommendations for the management of our patients with diabetes. 5
When our goal is to avoid hypoglycemia, as well as weight gain, the adapted recommendations are shown on this slide. 6
When patients with type 2 diabetes start their first injectable therapy, clinicians can choose between GLP-1 receptor agonists and basal insulin. In DURATION-3, exenatide once weekly was compared with insulin glargine as first injectable therapy. This three-year study demonstrated better control of hemoglobin A1C with exenatide once weekly than with insulin glargine. Compared with patients given glargine, those receiving exenatide lost rather than gained weight, and had a lower incidence of hypoglycemia. 7
SGLT-2 inhibitors block the reabsorption of filtered glucose by the proximal tubules of the kidneys, leading the glycosuria and improved glycemic control. This class of drugs has multiple additional benefits including weight loss and decreased blood pressure. Their action complements the action of other antidiabetic agents and, because they are independent of insulin, are associated with low rates of hypoglycemia. 8
This slide, which does not come from head-to-head studies, illustrates that the use of SGLT-2 inhibitors, whether used alone or as add-on to metformin or sulfonylurea, results in significant weight loss due to loss of mean body fat. 9
In addition, use of this class of drug is associated with significant reductions in blood pressure. 10
Here, we see that among our treatment options for patients with type 2 diabetes, the profiles for the DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors are better fit for Mathilda who is trying to lose weight and has hypertension, as well as episodes of hypoglycemia. 11
In light of Mathilda s hypoglycemia, I immediately discontinued her glimepiride. And, although her hemoglobin A1c was over 8.0, I wanted to avoid treatment with insulin at this point. We discussed her desire to lose weight, and I stressed the importance of a well-balanced diet with a regular exercise program. Since her renal function was normal, I continued metformin as foundation therapy and wanted to avoid TZDs, which could cause weight gain. Among the other choices, a DPP-4 inhibitor carries low risk of hypoglycemia and is weightneutral, whereas GLP-1 receptor agonists and SGLT-2 inhibitors are associated with weight loss and reduction in blood pressure as well as the low risk of hypoglycemia. So, to summarize, I feel the optimal treatment choice for Mathilda is a well-balanced diet with a regular exercise program, continuing treatment with metformin, and addition of an SGLT-2 inhibitor or a long-acting GLP-1 receptor agonist. 12