Insulin Analogs or Premixed Insulin Analogs in Combination With Oral Agents for Treatment of Type 2 Diabetes

Philip Levy, MD, FACE


April 16, 2007


In 2005, 20.8 million adults in the United States were estimated to have diabetes mellitus.[1] This number is expected to increase to 29 million by 2050.[2] Most cases of diabetes (90% to 95%) are type 2,[3] which has been increasing in prevalence everywhere in the United States in parallel with the obesity epidemic. All ages, ethnic groups, education levels, and both sexes are susceptible.[4]

Several long-term randomized trials of diabetes care and outcomes demonstrated that achieving near-normal glycemia, in terms of fasting and postprandial plasma glucose and glycosylated hemoglobin (A1C) levels, is crucial for avoiding or delaying long-term microvascular complications such as retinopathy, nephropathy, and neuropathy.[5,6,7] The evidence that intensive therapy also delays macrovascular disease is less compelling. However, after more than 17 years of follow-up in one of these trials, intensive insulin therapy that targeted normoglycemia was shown to reduce the risk of cardiovascular disease by 42%. Compared to conventional therapy (defined as 1-2 injections of insulin daily with no glycemic goals other than to prevent symptoms of hyperglycemia and hypoglycemia), the risk of nonfatal myocardial infarction, stroke, or death from cardiovascular disease was 57% lower with intensive therapy.[8]

Maintenance of tight glycemic control in patients with type 2 diabetes requires timely adjustments and changes in therapy when goals are not met. While the majority are initially treated with oral antidiabetic drugs (OADs),[9] most patients ultimately require insulin therapy to maintain glycemic control.[10] Commonly used OADs and some newer therapies have limited potential to lower A1C, by just 0.5 to 1.5%. Insulin, when used in appropriate doses, can decrease any level of A1C to near goal, limited only by its potential to cause hypoglycemia.[11] The aim of this article, therefore, is to provide evidence-based practical guidance for improving glycemic control in patients with type 2 diabetes. The emphasis is placed on how insulin therapy, in particular, with insulin analogs and premixed insulin analogs, can be initiated in patients who currently are inadequately managed with OADs alone.


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