Comparing Insulin Detemir With NPH Insulin as Add-On Therapy
Objective: To assess efficacy and tolerability of insulin detemir or NPH insulin added to oral therapy for type 2 diabetes in a treat-to-target titration protocol.
Research Design and Methods: Individuals (n = 476) with HbA1c (A1C) 7.5–10.0% were randomized to addition of twice-daily insulin detemir or NPH insulin in a parallel-group, multicenter trial. Over 24 weeks, insulin doses were titrated toward prebreakfast and predinner plasma glucose targets of ≤6.0 mmol/l (≤108 mg/dl). Outcomes assessed included A1C, percentage achieving A1C ≤7.0%, risk of hypoglycemia, and body weight.
Results: At 24 weeks, A1C had decreased by 1.8 and 1.9% (from 8.6 to 6.8 and from 8.5 to 6.6%) for detemir and NPH, respectively (NS). In both groups, 70% of participants achieved an A1C ≤7.0%, but the proportion achieving this without hypoglycemia was higher with insulin detemir than with NPH insulin (26 vs. 16%, P = 0.008). Compared with NPH insulin, the risk for all hypoglycemia with insulin detemir was reduced by 47% (P < 0.001) and nocturnal hypoglycemia by 55% (P < 0.001). Mean weight gain was 1.2 kg with insulin detemir and 2.8 kg with NPH insulin (P < 0.001), and the difference in baseline-adjusted final weight was –1.58 (P < 0.001).
Conclusions: Addition of basal insulin to oral drug therapy in people with suboptimal control of type 2 diabetes achieves guideline-recommended A1C values in most people with aggressive titration. Insulin detemir compared with NPH insulin achieves this with reduced hypoglycemia and less weight gain.
Improved glycemic control reduces incidence and delays progression of complications in type 2 diabetes. Treatment guidelines generally advocate HbA1c (A1C) targets of 6.5%, but clinical audits/studies suggest that many have difficulty achieving and maintaining such goals. An important contributory factor is a resistance to initiate insulin on the part of people with diabetes and care-givers. Insulin is usually added only after oral glucose-lowering drugs (OGLDs) fail to curtail hyperglycemia over extended periods, often when A1C exceeds 9.0%.
Delays in insulin initiation arise from fear of injections, psychological issues such as nonacceptance of treatment failure, and concerns about hypoglycemia and weight gain. However, blood glucose control is improved by introduction of insulin therapy. Insulin analogs have favorably shifted the achievable balance between glucose control and tolerability. In a recent study in which insulin glargine or NPH insulin was added to OGLDs with intensive titration, mean A1C was reduced from ~8.6% to just under 7.0% during 24 weeks, with 60% of patients achieving A1C <7.0%. The analog recipients benefited from reduced hypoglycemia, but there was no between-treatment difference in weight gain.
The present study used a similar treat-to-target design. Insulin detemir is an acylated insulin analog achieving extended action through self-association and reversible albumin binding. This and its solubility underpin a greater within-patient consistency in glucose-lowering time–action profile compared with other basal insulins. In clinical comparisons with NPH insulin in meal – time + basal therapy, insulin detemir was repeatedly associated with a reduced risk for nocturnal hypoglycemia and with less or absent weight gain at equivalent glycemic control.
These findings suggest that insulin detemir could be successfully added to OGLDs in people with inadequately controlled type 2 diabetes. We tested this hypothesis using active dose titration and glucose monitoring to determine the proportion of participants who could safely reach glycemic targets.
Objective: To assess efficacy and tolerability of insulin detemir or NPH insulin added to oral therapy for type 2 diabetes in a treat-to-target titration protocol.
Research Design and Methods: Individuals (n = 476) with HbA1c (A1C) 7.5–10.0% were randomized to addition of twice-daily insulin detemir or NPH insulin in a parallel-group, multicenter trial. Over 24 weeks, insulin doses were titrated toward prebreakfast and predinner plasma glucose targets of ≤6.0 mmol/l (≤108 mg/dl). Outcomes assessed included A1C, percentage achieving A1C ≤7.0%, risk of hypoglycemia, and body weight.
Results: At 24 weeks, A1C had decreased by 1.8 and 1.9% (from 8.6 to 6.8 and from 8.5 to 6.6%) for detemir and NPH, respectively (NS). In both groups, 70% of participants achieved an A1C ≤7.0%, but the proportion achieving this without hypoglycemia was higher with insulin detemir than with NPH insulin (26 vs. 16%, P = 0.008). Compared with NPH insulin, the risk for all hypoglycemia with insulin detemir was reduced by 47% (P < 0.001) and nocturnal hypoglycemia by 55% (P < 0.001). Mean weight gain was 1.2 kg with insulin detemir and 2.8 kg with NPH insulin (P < 0.001), and the difference in baseline-adjusted final weight was –1.58 (P < 0.001).
Conclusions: Addition of basal insulin to oral drug therapy in people with suboptimal control of type 2 diabetes achieves guideline-recommended A1C values in most people with aggressive titration. Insulin detemir compared with NPH insulin achieves this with reduced hypoglycemia and less weight gain.
Improved glycemic control reduces incidence and delays progression of complications in type 2 diabetes. Treatment guidelines generally advocate HbA1c (A1C) targets of 6.5%, but clinical audits/studies suggest that many have difficulty achieving and maintaining such goals. An important contributory factor is a resistance to initiate insulin on the part of people with diabetes and care-givers. Insulin is usually added only after oral glucose-lowering drugs (OGLDs) fail to curtail hyperglycemia over extended periods, often when A1C exceeds 9.0%.
Delays in insulin initiation arise from fear of injections, psychological issues such as nonacceptance of treatment failure, and concerns about hypoglycemia and weight gain. However, blood glucose control is improved by introduction of insulin therapy. Insulin analogs have favorably shifted the achievable balance between glucose control and tolerability. In a recent study in which insulin glargine or NPH insulin was added to OGLDs with intensive titration, mean A1C was reduced from ~8.6% to just under 7.0% during 24 weeks, with 60% of patients achieving A1C <7.0%. The analog recipients benefited from reduced hypoglycemia, but there was no between-treatment difference in weight gain.
The present study used a similar treat-to-target design. Insulin detemir is an acylated insulin analog achieving extended action through self-association and reversible albumin binding. This and its solubility underpin a greater within-patient consistency in glucose-lowering time–action profile compared with other basal insulins. In clinical comparisons with NPH insulin in meal – time + basal therapy, insulin detemir was repeatedly associated with a reduced risk for nocturnal hypoglycemia and with less or absent weight gain at equivalent glycemic control.
These findings suggest that insulin detemir could be successfully added to OGLDs in people with inadequately controlled type 2 diabetes. We tested this hypothesis using active dose titration and glucose monitoring to determine the proportion of participants who could safely reach glycemic targets.
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