Efficacy and safety of prandial premixed therapy using insulin lispro mix 50/50 3 times daily compared with progressive titration of insulin lispro mix 75/25 or biphasic insulin aspart 70/30 twice daily in patients with type 2 diabetes mellitus: a randomized, 16-week, open-label study.
BACKGROUND
Prandial premixed therapy 3 times daily has been proposed recently for type 2 diabetes mellitus (T2DM) patients who fail to achieve glycemic control with commonly used premixed insulin analogs, insulin lispro mix 75/25 (LM75/25) and biphasic insulin aspart 70/30 (BIAsp70/30) BID.


OBJECTIVE
The aim of this work was to compare the efficacy and safety of 3-times daily insulin lispro mix 50/50 (TID group) with progressive titration of twice-daily LM75/25 or BIAsp70/30 (BID group) administered along with metformin in T2DM patients.


METHODS
This was an open-label, 16-week, multicenter, randomized, parallel trial. End point glycosylated hemoglobin (HbA(1c)) was the primary efficacy measure; HbA(1c) reduction from baseline to end point, percentage of patients reaching target HbA(1c) (<7.0% and ≤6.5%), postprandial blood glucose (BG), and BG excursions after lunch were secondary measures. Safety was evaluated by collecting adverse events.


RESULTS
A total of 302 patients with mean (SD) age 57.7 (9.27) years, diabetes duration 11.2 (6.47) years, HbA(1c) 8.5% (1.23), fasting BG 184.0 (53.04) mg/dL, body weight 86.8 (14.79) kg, body mass index 31.7 (4.23) kg/m(2), and daily insulin dose ∼48 IU were randomized. No significant difference was observed in end point HbA(1c) between the 2 groups. Seven-point BG profiles showed lower fasting and postbreakfast BG in the BID group but lower postlunch BG in the TID group. Daily insulin dose change was similar in both groups, with more weight gain in the TID group (P = 0.0009). Overall hypoglycemic rates were similar in both groups, but nocturnal hypoglycemia was more frequent in the BID group (P = 0.0063).


CONCLUSIONS
In patients with T2DM who have not achieved adequate glycemic control with LM75/25 and BiAsp70/30 BID plus metformin and who are not candidates for basal bolus therapy, switching either to treatment with LM50/50 TID or to progressive titration of premix insulin analogs BID did not produce sufficient evidence of a difference of overall glycemic control between the 2 treatment groups. Short study duration and less intensive dose adjustments might have contributed to these results.
NC Paulescu National Diabetes, Nutrition, and Metabolic Diseases Institute, Bucharest, Romania.
Eugenia
E
Farcasiu
Tibor
T
Ivanyi
Barbara
B
Mozejko-Pastewka
Zita
Z
Birkus
Jozsef
J
Csog
Irina
I
Kowalska
Thomas Frederic
TF
Coetzer
Sami
S
Bulgurlu
Birgit
B
Schinzel
Jacek
J
Kiljanski
D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004435:Eating; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061267:Insulin Aspart / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061268:Insulin Lispro / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D061267:Insulin Aspart; D061268:Insulin Lispro