Rapid-acting insulin at mealtimes decreases postprandial hyperglycemia

Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 45-year-old woman is seen for routine follow-up. She has type 2 diabetes mellitus, diagnosed 5 years ago; initial treatment included metformin and glimepiride. A daily injection of insulin glargine was added to her regimen 1 year ago.

At present, her hemoglobin A_1c value is 8.1%. Mean blood glucose values derived from the past 4 days of the patient’s blood glucose log, which includes preprandial and postprandial values, are shown.

Breakfast: preprandial, 105 mg/dL (5.8 mmol/L); postprandial, 186 mg/dL (10.3 mmol/L)
Lunch: preprandial, 169 mg/dL (9.4 mmol/L); postprandial, 258 mg/dL (14.3 mmol/L)
Supper: preprandial, 146 mg/dL (8.1 mmol/L); postprandial, not measured.

Her mean bedtime blood glucose level is 278 mg/dL (15.4 mmol/L).

Which of the following changes should be made to this patient’s medication regimen?

A) Add exenatide
B) Increase the insulin glargine dosage
C) Start insulin pump therapy
D) Stop glimepiride and add mealtime insulin aspart

MKSAP Answer and Critique

The correct answer is D) Stop glimepiride and add mealtime insulin aspart. This item is available to MKSAP 15 subscribers as item 11 in the Endocrinology and Metabolism section.

This patient’s medication regimen should be altered by stopping the glimepiride and initiating mealtime insulin aspart. Patients with type 2 diabetes mellitus experience progressive beta cell dysfunction, which eventually results in the requirement of insulin in most patients. Insulin therapy is typically begun with a single injection of a basal insulin, such as insulin glargine or insulin detemir, or two injections of neutral protamine Hagedorn (NPH) insulin. Over time, insulin secretion becomes progressively deficient, and postprandial glucose excursions can no longer be addressed by increasing the basal insulin dose. Such a scenario requires the addition of a rapid-acting insulin analogue before meals. Insulin lispro, insulin aspart, and insulin glulisine are typically used in this setting in dosages sufficient to prevent the glucose level from increasing more than 40 to 60 mg/dL (2.2 to 3.3 mmol/L) with each meal. Once this more intensive insulin regimen is initiated, ongoing use of a sulfonylurea, such as glimepiride, is no longer required.

Exenatide does reduce postprandial glucose levels and may be effective in doing so for this patient. However, exenatide was not initially approved for use with insulin. In 2011, a clinical trial on the use of exenatide with insulin glargine demonstrated that it was safe and effective, and the contraindication of basal insulin co-administration was subsequently removed from the product label. Regardless, the addition of prandial insulin to insulin glargine is still the preferred approach in this patient because of expense, lack of long-term safety data, and need for confirmatory clinical trials demonstrating efficacy of combination therapy with exenatide and insulin.

Increasing this patient’s insulin glargine dosage will not address her prandial insulin requirements because glargine is a basal insulin and does not control postprandial glycemic peaks.

Continuous subcutaneous insulin infusion using an insulin pump is becoming a viable treatment option for patients with type 2 diabetes. Patients who may benefit from an insulin pump include those who have not been able to achieve glycemic goals on an intensified insulin regimen of multiple daily injections; have unacceptable rates of hypoglycemia when following insulin injection regimens that combine intermediate- or long-acting insulin (NPH, glargine) with prandial insulin; have a marked dawn phenomenon (increase in blood glucose levels during the early morning hours, i.e., 4:00 a.m. to 8:00 a.m.); or have erratic lifestyles (travel, shift work). Insulin pump therapy is premature at this juncture because this patient has not had a trial of an intensified insulin regimen of multiple daily injections.

Key Point

The addition of rapid-acting insulin analogues at mealtimes decreases postprandial glycemic excursions.

Learn more about ACP’s MKSAP 16.

This content is excerpted from MKSAP 15 with permission from the American College of Physicians (ACP). Use is restricted in the same manner as that defined in the MKSAP 15 Digital license agreement. This material should never be used as a substitute for clinical judgment and does not represent an official position of ACP. All content is licensed to KevinMD.com on an “AS IS” basis without any warranty of any nature. The publisher, ACP, shall not be liable for any damage or loss of any kind arising out of or resulting from use of content, regardless of whether such liability is based in tort, contract or otherwise.