Comparison of Two Types of Insulin Added to Diabetes Pills in Poorly Controlled Type 2 Diabetes

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The summary below is from the full report titled "Addition of Neutral Protamine Lispro Insulin or Insulin Glargine to Oral Type 2 Diabetes Regimens for Patients with Suboptimal Glycemic Control. A Randomized Trial." It is in the 21 October 2008 issue of Annals of Internal Medicine (volume 149, pages 531-539). The authors are K. Esposito, M. Ciotola, M.I. Maiorino, R. Gualdiero, B. Schisano, A. Ceriello, F. Beneduce, G. Feola, and D. Giugliano.

What is the problem and what is known about it so far?

Type 2 diabetes mellitus interferes with the body's ability to store energy from food, resulting in high blood sugar levels that can lead to such problems as kidney failure, blindness, and heart disease. Insulin helps the body to convert food to stored energy and keeps blood sugar levels within the normal range. In type 2 diabetes, body tissues are resistant to the effects of insulin and patients lack effective insulin levels that are required to keep their blood sugar levels normal. Some patients can overcome the abnormalities with prescription pills. However, sugar levels often remain high despite the pills, and patients need to add insulin injections to their treatment. Different types of prescription insulins vary in how long they are active. Short-acting insulins act quickly and can lower blood sugar levels too much and too quickly in many patients. For this reason, long-acting insulins are often used when insulin is added to diabetes pills. Neutral protamine lispro (NPL), a newer insulin, is one such long-acting insulin, and insulin glargine is another.

Why did the researchers do this particular study?

To compare diabetes control when patients with poor control receiving pills alone add either NPL or glargine insulin to their diabetes treatment regimen.

Who was studied?

116 adults with type 2 diabetes who were receiving 2 diabetes pills (metformin and sulfonylurea) and had hemoglobin A_1c levels of 7.5% to 10% and fasting blood sugar levels greater than 6.7 mmol/L (>120 mg/dL). A normal fasting blood sugar level is about 5.6 mmol/L (100 mg/dL). The hemoglobin A_1c is a blood test that measures blood sugar control over the previous 3 months. Lower levels mean better control, and the recommended target is less than 7%.

How was the study done?

Patients continued to receive their diabetes pills, along with a bedtime injection of either 10 units of NPL insulin or insulin glargine. Patients adjusted the insulin dose every week to achieve fasting blood sugar levels less than 5.6 mmol/L (<100 mg/dL). The researchers measured the change in hemoglobin A_1c over 36 weeks, the numbers of patients who had a hemoglobin A_1c level less than 7%, patient-reported episodes of low blood sugar (hypoglycemia), body weight, and total insulin dose. Of the 116 patients, 20 also had their sugar levels measured continuously over 3 days with a device that is inserted under the skin to measure sugar levels every few minutes.

What did the researchers find?

No differences were found among any of the measured outcomes between patients who received NPL and those who received glargine.

What were the limitations of the study?

The study may have been too small to detect differences in the frequency of low blood sugar episodes between the 2 insulins. Only 40 of the 116 patients had continuous monitoring of their sugar level, and monitoring lasted for only 3 days. It is possible that patients were having low blood sugar levels that did not result in symptoms and were not detected because of the lack of continuous monitoring.

What are the implications of the study?

Neutral protamine lispro and insulin glargine result in similar diabetes control when added to metformin and sulfonylurea in patients with poor control who are receiving pills alone. There was no advantage of 1 insulin over the other.