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AHRQ--Agency for Healthcare Research and Quality: Advancing Excellence in Health Care
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Comparative Effectiveness Review: Premixed Insulin Analogues for Adults With Type 2 Diabetes

Although oral diabetes medicines are used as first-line treatments in patients with type 2 diabetes, insulin is often required to achieve the desired level of glucose control. According to the National Health Interview Survey, 28 percent of patients with type 2 diabetes use insulin either alone (16 percent) or in combination with oral diabetes medicines (12 percent). 

To mimic the release of insulin from the pancreas in response to food intake, insulin replacement regimens involve giving insulin at mealtimes along with a longer-acting insulin that provides a slow release of insulin throughout the day. However, these insulin regimens may decrease a person’s flexibility in the timing of meals and activities, increase the frequency of blood glucose monitoring, and increase the risk of hypoglycemia. Also, the requirement of multiple injections may affect patients’ overall satisfaction with their treatment regimen.

Premixed insulin preparations are an alternative that may permit a smaller number of daily insulin injections. They combine both mealtime insulin and a longer lasting insulin. The newest premixed insulin preparations use insulin analogues, which are insulins with amino acid substitutions that alter their rate of entering the bloodstream after a subcutaneous injection. It is important to evaluate the evidence for the safety and effectiveness of these premixed insulins compared with other regimens for managing blood glucose. The EHC Program commissioned the Evidence-based Practice Center at Johns Hopkins University to perform a systematic review of premixed insulin analogues. The review found that:

  • There is more evidence available on some comparisons than others. When compared with premixed NPH (neutral protamine Hagedorn) and regular insulin, people who use premixed insulin analogues achieve similar reductions in A1c (average blood glucose) and fasting glucose levels, but those who use premixed insulin analogues achieve lower glucose levels after meals. Rates of hypoglycemia are also similar.
  • People who use premixed insulin analogues achieve lower A1c levels than people who use long-acting insulin analogues alone, but rates of hypoglycemia are higher.
  • People who use premixed insulin analogues experience more episodes of hypoglycemia but also achieve better glycemic control than those who use oral diabetes drugs.

Evidence was insufficient to determine whether the effectiveness or harms of premixed insulin analogues vary by demographic factors. There was insufficient evidence to draw conclusions about the effectiveness of premixed insulin analogues for people with poor glycemic control or coexisting medical conditions. There was also insufficient evidence about the impact of premixed insulin analogues on quality of life and treatment satisfaction. Most available studies of premixed insulin analogues lasted 1 year or less and focused on short-term outcomes. Therefore, evidence was insufficient to determine the effects of premixed insulin analogues on long-term outcomes, such as mortality and cardiovascular disease.

Further information about the CER, including both an Executive Summary and the complete report, is available.