Long vs. Intermediate Acting Insulin for Type 1 Diabetes
Long vs. Intermediate Acting Insulin for Type 1 Diabetes
Objective. To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes.
Design. Systematic review and network meta-analysis.
Data Sources. Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013.
Study Selection. Randomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included.
Results. 39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A1c compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference −0.39%, 95% confidence interval −0.59% to −0.19%; −0.26%, −0.48% to −0.03%; and −0.36%, −0.65% to −0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: −5.51 kg, −6.56 to −4.46 kg; glargine once daily versus NPH once daily: −5.14 kg, −6.07 to −4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses.
Conclusions. Long acting insulin analogs are probably superior to intermediate acting insulin analogs, although the difference is small for hemoglobin A1c. Patients and their physicians should tailor their choice of insulin according to preference, cost, and accessibility.
Systematic Review Registration. PROSPERO CRD42013003610.
To treat hyperglycemia associated with type 1 diabetes, insulin is administered; isophane insulin (neutral protamine Hagedorn (NPH)) and zinc insulin (lente) have been used commonly since the 1950s. Newer insulin analogs (for example, glargine, detemir) are reported to have a longer duration of action and less between patient variability; they have been available since the early 2000s.
Some evidence suggests that the newer long acting insulin analogs such as glargine and detemir might be more effective and safer than intermediate acting insulin (NPH and lente). Although systematic reviews exist on this topic, only efficacy data from randomized trials were analyzed and comparative effectiveness data from observational studies were not included. Furthermore, cost effectiveness data were not considered in these reviews. We did a systematic review and network meta-analysis to examine the comparative effectiveness, safety, and cost effectiveness of long acting insulin versus intermediate acting insulin for patients with type 1 diabetes.
Abstract and Introduction
Abstract
Objective. To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes.
Design. Systematic review and network meta-analysis.
Data Sources. Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013.
Study Selection. Randomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included.
Results. 39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A1c compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference −0.39%, 95% confidence interval −0.59% to −0.19%; −0.26%, −0.48% to −0.03%; and −0.36%, −0.65% to −0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: −5.51 kg, −6.56 to −4.46 kg; glargine once daily versus NPH once daily: −5.14 kg, −6.07 to −4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses.
Conclusions. Long acting insulin analogs are probably superior to intermediate acting insulin analogs, although the difference is small for hemoglobin A1c. Patients and their physicians should tailor their choice of insulin according to preference, cost, and accessibility.
Systematic Review Registration. PROSPERO CRD42013003610.
Introduction
To treat hyperglycemia associated with type 1 diabetes, insulin is administered; isophane insulin (neutral protamine Hagedorn (NPH)) and zinc insulin (lente) have been used commonly since the 1950s. Newer insulin analogs (for example, glargine, detemir) are reported to have a longer duration of action and less between patient variability; they have been available since the early 2000s.
Some evidence suggests that the newer long acting insulin analogs such as glargine and detemir might be more effective and safer than intermediate acting insulin (NPH and lente). Although systematic reviews exist on this topic, only efficacy data from randomized trials were analyzed and comparative effectiveness data from observational studies were not included. Furthermore, cost effectiveness data were not considered in these reviews. We did a systematic review and network meta-analysis to examine the comparative effectiveness, safety, and cost effectiveness of long acting insulin versus intermediate acting insulin for patients with type 1 diabetes.
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