Diabetes: a journal of the American Diabetes Association by American Diabetes Association; Stanford University. Copyright 2004. Reproduced with permission of AMERICAN DIABETES ASSOCIATION in the format Journal via Copyright Clearance Center.
Insulin detemir was reported to have significantly less intraindividual pharmacodynamic variability compared with insulin glargine and NPH insulin. The variability (as assessed by the coefficient of variation) of the glucose infusion rate area under the curve for the first 12 hours was 27% for detemir, 46% for glargine, and 59% for NPH insulin (P < .001 vs insulin glargine and NPH insulin). Over the first 24 hours, the coefficients of variation were 27% for detemir, 48% for glargine, and 68% for NPH insulin (P < .001 vs insulin glargine and NPH insulin). With respect to pharmacokinetics, the coefficients of variation of the maximum plasma insulin concentration were 18% for detemir, 34% for glargine, and 24% for NPH insulin.
Despite these pharmacodynamic and pharmacokinetic differences favoring the basal insulin analogs compared with NPH insulin, evidence-based systematic reviews have concluded that overall glucose control is similar among the 3 basal insulins.28,33 These findings should be interpreted cautiously since the basal insulins were generally administered once daily in the studies included in the systematic reviews, although a few studies used a twice-daily regimen for insulin detemir or NPH insulin.28 Furthermore, some of the studies included in the systematic reviews used a treat-to-target design, in which equal glucose-lowering efficacy was maintained among treatments, thereby allowing comparisons of other insulin properties. An important difference between the basal insulin analogs and NPH insulin identified in the systematic reviews concerns hypoglycemia, particularly nocturnal hypoglycemia. Detemir and glargine were associated with significant reductions in nocturnal hypoglycemia compared with NPH insulin (both, relative risk [RR]=.54; P < .001). The risk for overall hypoglycemia was also reported to be lower with insulin detemir and insulin glargine compared with NPH insulin (RR=.68 and RR=.89, respectively; P < .001 and P=.002). The risk for severe hypoglycemia was similar for insulin glargine or insulin detemir compared with that of NPH insulin.
A recent meta-analysis comparing insulin glargine (once daily) to insulin detemir (once or twice daily) examined data from 4 trials lasting 24 to 52 weeks and involving 2250 people.34 The meta-analysis found no differences between the 2 basal insulin analogs with respect to glycemic control, as measured by the percentage of patients who achieved A1C ≤7.0% with or without hypoglycemia. In addition, no significant differences in overall, severe, and nocturnal hypoglycemia were identified. Insulin detemir was associated with less weight gain and insulin glargine with a lower number of injection-site reactions.
Evolution of Insulin Delivery
In addition to progressive improvements in purity and the time-action profile of insulin, there have been major advances in the devices used to deliver insulin that provide clinicians greater flexibility to meet patients’ needs and to resolve patients’ concerns. Advances in delivery systems include pens with shorter, smaller gauge, highly polished needles; pens with a “dial-a-dose” gauge that is easier to read; easy portability; and insulin-prefilled pens. These advances improve ease of use and dosage accuracy, likely reduce injection pain, facilitate discrete use in public places, and increase patient acceptance and adherence.35-42 Of note, however, insulin pens must never be used in more than one individual, even if a needle has been changed, as is sometimes done in institutions. A clinical reminder from the US Centers for Disease Control and Prevention in January 2012 cautioned against pen reuse and sharing, citing an incident in which more than 2000 individuals were potentially exposed to the transmission of bloodborne pathogens because of inappropriate reuse and sharing of insulin pens.43 Another advance in insulin delivery is insulin-pump therapy, which has become even more promising with the advent of continuous glucose-monitoring devices and the availability of rapid-acting insulin analogs.
Role of Insulin in Diabetes
Recently, insulin has been recognized as a key treatment option for patients with T2DM, and is no longer considered last-line therapy.4,44 When used appropriately, insulin is the most effective glucose-lowering therapy available, with essentially no limit to the magnitude of glucose lowering. Insulin, particularly the insulin analogs, provides many treatment benefits, although some limitations remain.
Benefits of Insulin
Basal-bolus therapy using the combination of a rapid-acting insulin analog and a basal insulin analog may closely mimic the release of insulin from the pancreatic β cells. The use of an insulin pump, which uses only a rapid- or short-acting insulin (rapid-acting analog preferred) may also provide insulin in a pattern that most closely mimics endogenous insulin secretion. The administration of insulin via an insulin pump may be a good treatment option in patients with T1DM or those with T2DM who require intensive basal-bolus therapy.
