Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study.
OBJECTIVE
In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA(1c); secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia.


METHODS
In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA(1c) >or=8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups.


RESULTS
During the last 12 weeks, FPGs averaged 5.75+/-0.02 and 5.96+/-0.03 mmol/l (p<0.001) and insulin doses were 68+/-5 and 70+/-6 IU/day (0.69+/-0.05 and 0.66+/-0.04 IU kg(-1) day(-1), NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA(1c) was 7.14+/-0.12 and 7.16+/-0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1+/-0.8 episodes/patient-year) than in the NPH+MET group (9.0+/-2.3 episodes/patient-year, p<0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1+/-0.3 mmol/l) than in the G+MET group (8.6+/-0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA(1c) <7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7+/-0.2 vs 6.7+/-0.3 mmol/l for patients reaching vs those not reaching target, p<0.01).


CONCLUSIONS
Good glycaemic control can be achieved with both G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinner time hyperglycaemia compared with NPH+MET.
Yki-Järvinen
H
H
Department of Medicine, University of Helsinki, P.O. Box 340, FIN-00029 HUCH, Helsinki, Finland. ykijarvi@cc.helsinki.fi
Kauppinen-Mäkelin
R
R
Tiikkainen
M
M
Vähätalo
M
M
Virtamo
H
H
Nikkilä
K
K
Tulokas
T
T
Hulme
S
S
Hardy
K
K
McNulty
S
S
Hänninen
J
J
Levänen
H
H
Lahdenperä
S
S
Lehtonen
R
R
Ryysy
L
L
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005215:Fasting; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000097:blood; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000009:adverse effects / Q000627:therapeutic use*; D049528:Insulin, Long-Acting; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000201:enzymology; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D000069036:Insulin Glargine; D007336:Insulin, Isophane; D049528:Insulin, Long-Acting; D008687:Metformin