Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial.
OBJECTIVE
To study the effect of insulin treatment in combination with metformin or an insulin secretagogue, repaglinide, on glycaemic regulation in non-obese patients with type 2 diabetes.


METHODS
Randomised, double blind, double dummy, parallel trial.


METHODS
Secondary care in Denmark between 2003 and 2006.


METHODS
Non-obese patients (BMI </=27) with preserved beta cell function.


METHODS
After a four month run-in period with repaglinide plus metformin combination therapy, patients with a glycated haemoglobin (HbA(1c)) concentration of 6.5% or more were randomised to repaglinide 6 mg or metformin 2000 mg. All patients also received biphasic insulin aspart 70/30 (30% soluble insulin aspart and 70% intermediate acting insulin aspart) 6 units once a day before dinner for 12 months. Insulin dose was adjusted aiming for a fasting plasma glucose concentration of 4.0-6.0 mmol/l. The target of HbA(1c) concentration was less than 6.5%. Treatment was intensified to two or three insulin injections a day if glycaemic targets were not reached.


METHODS
HbA(1c) concentration.


RESULTS
Of the 459 patients who were eligible, 102 were randomised, and 97 completed the trial. Patients had had type 2 diabetes for approximately 10 years. At the end of treatment, HbA(1c) concentration was reduced by a similar amount in the two treatment groups (insulin plus metformin: mean (standard deviation) HbA(1c) 8.15% (1.32) v 6.72% (0.66); insulin plus repaglinide: 8.07% (1.49) v 6.90% (0.68); P=0.177). Total daily insulin dose and risk of hypoglycaemia were also similar in the two treatment groups. Weight gain was less with metformin plus biphasic insulin aspart 70/30 than with repaglinide plus biphasic insulin aspart 70/30 (difference in mean body weight between treatments -2.51 kg, 95% confidence interval -4.07 to -0.95).


CONCLUSIONS
In non-obese patients with type 2 diabetes and poor glycaemic regulation on oral hypoglycaemic agents, overall glycaemic regulation with insulin in combination with metformin was equivalent to that with insulin plus repaglinide. Weight gain seemed less with insulin plus metformin than with insulin plus repaglinide.


BACKGROUND
NCT00118963.
Lund
Søren S
SS
Steno Diabetes Center, Gentofte, Denmark. sqrl@steno.dk
Tarnow
Lise
L
Frandsen
Merete
M
Nielsen
Bente B
BB
Hansen
Birgitte V
BV
Pedersen
Oluf
O
Parving
Hans-Henrik
HH
Vaag
Allan A
AA
D001786:Blood Glucose / Q000378:metabolism; D002219:Carbamates / Q000008:administration & dosage* / Q000009:adverse effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000009:adverse effects / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D061267:Insulin Aspart; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010349:Patient Compliance; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D015430:Weight Gain
D001786:Blood Glucose; D002219:Carbamates; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart; D008687:Metformin; D010880:Piperidines; C072379:repaglinide