Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes.
OBJECTIVE
To compare the efficacy and safety of adding once-daily basal insulin versus switching to twice-daily premixed insulin in type 2 diabetic patients insufficiently controlled by oral antidiabetic agents (OADs).


METHODS
In a 24-week, multinational, multicenter, open, parallel group clinical trial, 371 insulin-naive patients with poor glycemic control (fasting blood glucose [FBG] >/=120 mg/dl, HbA(1c) 7.5-10.5%) on OADs (sulfonylurea plus metformin) were randomized to once-daily morning insulin glargine plus glimepiride and metformin (glargine plus OAD) or to 30% regular/70% human NPH insulin (70/30) twice daily without OADs. Insulin dosage was titrated to target FBG </=100 mg/dl (both insulins) and predinner blood glucose </=100 mg/dl (70/30 only) using a weekly forced-titration algorithm.


RESULTS
Mean HbA(1c) decrease from baseline was significantly more pronounced (-1.64 vs. -1.31%, P = 0.0003), and more patients reached HbA(1c) </=7.0% without confirmed nocturnal hypoglycemia (45.5 vs. 28.6%, P = 0.0013) with glargine plus OAD than with 70/30. Similarly, FBG decrease was greater with glargine plus OAD (adjusted mean difference -17 mg/dl [-0.9 mmol/l], P < 0.0001), and more patients reached target FBG </=100 mg/dl with glargine plus OAD than with 70/30 (31.6 vs. 15.0%, P = 0.0001). Glargine plus OAD patients had fewer confirmed hypoglycemic episodes than 70/30 patients (mean 4.07 vs. 9.87/patient-year, P < 0.0001).


CONCLUSIONS
Initiating insulin treatment by adding basal insulin glargine once daily to glimepiride plus metformin treatment was safer and more effective than beginning twice-daily injections of 70/30 and discontinuing OADs in type 2 diabetic patients inadequately controlled with OADs.
Janka
Hans U
HU
Zentralkrankenhaus, Bremen-Nord, II Medizinische Abteilung, Hammersbecker Str. 228, 28755 Bremen, Germany. hans.janka@klinikum-bremen-nord.de
Plewe
Gerd
G
Riddle
Matthew C
MC
Kliebe-Frisch
Christine
C
Schweitzer
Matthias A
MA
Yki-Järvinen
Hannele
H
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D013453:Sulfonylurea Compounds; D000069036:Insulin Glargine; C057619:glimepiride; D008687:Metformin