Basal supplementation of insulin lispro protamine suspension versus insulin glargine and detemir for type 2 diabetes: meta-analysis of randomized controlled trials

Abstract

Objective: We compared the effect of insulin lispro protamine suspension (ILPS) with that of insulin glargine and insulin detemir, all given as basal supplementation, in the treatment of patients with type 2 diabetes.

Research design and methods: We conducted an electronic search until February 2012, including online registries of ongoing trials and abstract books. All randomized controlled trials comparing ILPS with insulin glargine or detemir with a duration of ≥12 weeks were included.

Results: We found four trials lasting 24-36 weeks involving 1,336 persons: three studies compared ILPS with glargine, and one trial compared ILPS with detemir. There was no significant difference in change in HbA(1c) level between ILPS and comparators, in the proportion of patients achieving the HbA(1c) goals of ≤6.5 or <7%, in weight change, or in daily insulin doses. There was no difference in overall hypoglycemia, but nocturnal hypoglycemia occurred significantly more with ILPS than with comparator insulins (mean difference 0.099 events/patient/30 days [95% CI 0.03-0.17]). In a prespecified sensitivity analysis comparing data obtained in patients who remained on their once-daily insulin regimen, not significantly different event rates for nocturnal hypoglycemia were observed between ILPS and comparator insulins (0.063 [-0.007 to 0.13]), and ILPS was associated with lower insulin dose (0.07 units/kg/day [0.05-0.09]).

Conclusions: There is no difference between ILPS and insulin glargine or detemir for targeting hyperglycemia, but nocturnal hypoglycemia occurred more frequently with ILPS than with comparator insulins. Nocturnal hypoglycemia was not significantly different in people who injected insulin once daily.

Figure 1

Change in HbA_1c level from baseline was not different between ILPS and comparators (glargine or detemir) either in full analysis (top panel) or in sensitivity analysis comparing patients who remained on their once-daily insulin regimen (bottom panel). Comparator insulins better on the right and ILPS better on the left. WMD, weighted mean difference. (A high-quality color representation of this figure is available in the online issue.)

Figure 2

Nocturnal hypoglycemia was significantly more frequent in patients assigned to ILPS than comparators (glargine or detemir) in full analysis (top panel) but not in sensitivity analysis comparing patients who remained on their once-daily insulin regimen (bottom panel). Comparator insulins better on the right and ILPS better on the left. WMD, weighted mean difference. (A high-quality color representation of this figure is available in the online issue.)