Glucose Control and Avoidance of Hypoglycemia

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This month, American Society of Endocrine PAs President Chris Sadler, MA, PA-C, CDE, responds to a reader query about how to achieve glucose control while balancing the risks for hypoglycemia and hyperglycemia. In the process, he discusses the recently published guidelines from the American Diabetes Association and the European Association for the Study of Diabetes.


Q: I am frustrated by the “always bring the blood sugars down slowly” philosophy, which I know is intended to avoid hypoglycemic symptoms. However, it often seems to be done at the expense of prolonged hyperglycemia, which is dangerous for patients’ long-term health and may cause more rapid beta-cell destruction. What’s the deal?

There is evidence that rapid achievement of tight glucose control using intensive insulin therapy with multiple daily injections or insulin pumps in patients with newly diagnosed type 2 diabetes has favorable outcomes on recovery and maintenance of beta-cell function and prolonged glycemic remission, compared with treatment with oral hypoglycemic agents.1 However, this approach is time consuming and not practical in most primary care settings.

Overcoming “clinical inertia” (the failure to initiate or intensify therapy when indicated) has been identified as a major barrier to achieving rapid glycemic control, to the detriment of the patient’s health. One recent study showed that more frequent follow-up with a multidisciplinary team and regular use of a computer-analyzed 7-point glucose profile resulted in more rapid and significantly better glycemic control with a lower A1C, compared to standard care.2 This approach is much more practical in a primary care setting.

Additionally, we always treat our patients as individuals. There are very few maxims that are correct in all situations. Almost every answer to a clinical question begins with the qualifier “It depends….” The specifics of the individual case will clarify the appropriate answer.

In regard to this particular question, the answer will vary by the clinical history of the patient. For example, for a pregnant patient with poor glycemic control, potential hospitalization and rapid titration of insulin would be the most judicious plan. In this case, quickly bringing glucose into tight control helps minimize risks to the developing fetus. However, if the patient is a frail 80-year-old with advanced cardiovascular disease, then slow and careful titration of medications would be the prudent course to meticulously avoid hypoglycemia.

New guidelines from the American Diabetes Association and the European Association for the Study of Diabetes (ADA/EASD)3 are helpful in that they identify various clinical issues and give guidance on which medication regimens would be more appropriate for the specific clinical history. They categorize medications based on efficacy, weight gain, hypoglycemia, major side effects, and costs.

Guidelines from the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE)4 are also very useful, because they categorize treatment based on the A1C level, as well as potential for weight gain and hypoglycemia. For example, a patient with an A1C < 7.5% may be an appropriate candidate for monotherapy, while a symptomatic patient with an A1C > 9% would likely benefit from insulin therapy or triple oral agent therapy.

First, it is helpful to set individual glycemic targets for your patient. The following factors can help you in determining A1C targets:

• Psychosocial considerations (motivation, adherence to therapy, self-care capacity)

• Resources or support systems (family support, community resources, living situation, etc)

• Risk for hypoglycemia

• Duration of diabetes

• Life expectancy

• Microvascular complications

• Cardiovascular disease and coexisting conditions.

For example, an older individual with poor motivation, lack of support systems, short life expectancy, and coexisting terminal cancer would have a less stringent A1C target of ≤ 8%, whereas a young, motivated individual with no complications or serious coexisting complications would have an A1C target of 6%.

The new ADA/EASD guidelines list additional considerations for medication choices for various comorbidities, including coronary disease, heart failure, renal disease, liver dysfunction, and hypoglycemia. For each comorbidity listed, there are suggested medications that are preferred and those that should be avoided.

If your goal is to avoid hypoglycemia, the ADA/EASD guidelines list medication choices that have low propensity to cause hypoglycemia (eg, metformin, pioglitazone, DPP-4 inhibitors, and GLP-1 receptor agonists). (Of note, special attention is given to medications that do not cause weight gain, such as GLP-1 receptor agonists, DPP-4 inhibitors, and metformin.)

Finally, the consensus statement emphasizes the need for individualizing therapy. Many patients have multiple comorbidities and may have medication sensitivities, cost constraints, etc. All of these factors must be taken into consideration when making therapeutic choices.

Keep in mind, “one size does not fit all” when it comes to diabetes therapy. The recent releases from both the ADA/EASD and AACE/ACE give us much more detailed guidance addressing medication choices in regard to efficacy, potential for hypoglycemia and weight gain, major side effects, and costs.

As always, guidelines do not replace good clinical judgment, based on the patient sitting in front of you.

1. Weng J, Li Y, Xu W, et al. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomized parallel-group trial. Lancet. 2008;371 (9626):1753-1760.

2. Pimazoni-Netto A, Rodbard D, Zanella MT; Diabetes Education and Control Group. Rapid improvement of glycemic control in type 2 diabetes using weekly intensive multifactorial interventions: structured glucose monitoring, patient education, and adjustment of therapy—a randomized controlled trial. Diabetes Technol Therapeutics. 2011;13(10):997-1004.

3. Inzucchi SE, Bergenstahl RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient centered approach. Diabetes Care. [Epub ahead of print; April 19, 2012].

4. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009;15(6):540-559.

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