Prandial insulin substitution with insulin lispro or insulin lispro, mid mixture vs. basal therapy with insulin glargine:: A randomized controlled trial in patients with type 2 diabetes beginning insulin therapy

Purpose: To compare the effects of prandial insulin therapy focusing on postprandial glucose control vs. basal insulin therapy focusing on fasting glucose control in patients with type 2 diabetes. Methods: This was an open-label, randomized, parallel, three-arm multicenter trial in patients with type 2 diabetes starting insulin treatment. Patients (n=159) were randomly assigned to 24-week treatment with 3 x daily insulin lispro, 3 x daily lispro mid Mixture (MidMix; 50% lispro, 50% protaminated lispro), or 1 x daily insulin glargine; oral antihyperglycemic agents were discontinued. Primary end point was the postprandial glucose excursion 2 h after breakfast at the end of study. Secondary outcomes included HbA(1c), self-monitored blood glucose profiles, hypoglycemic episodes, body weight, and patient satisfaction. Results: At the end of study, glucose excursions 2 h after breakfast were significantly lower with lispro and MidMix than with glargine (P < .001 for each vs. glargine): lispro, -0.6 +/- 2.0 mmol/l; MidMix, +0.8 +/- 2.4 mmol/l; glargine, +2.5 +/- 2.4 mmol/l. Fasting glucose decreases were significantly greater with glargine (-2.6 +/- 2.4 mmol/l) than with lispro or MidMix (-0.9 +/- 2.2 mmol/l; +0.9 +/- 1.8 mmol/l). Nevertheless, HbA(1c) decreased by 1.1% (lispro) and 1.2% (MidMix), vs. 0.3% with glargine. Hypoglycemic episodes were rare with 1-1.5 self-reported episodes per 100 patient days. Conclusions: In patients with type 2 diabetes starting insulin, 3 x daily prandial treatment with a rapid-acting analog focusing on postprandial glucose values enabled better control of postprandial and circadian blood glucose profiles than once-daily glargine.. in spite suboptimal fasting glucose levels, which targets fasting glucose values. These results support studies suggesting that control of postprandial hyperglycemia plays a key role in achieving HbA(1c) targets. (c) 2006 Elsevier Inc. All rights reserved.