Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes.
OBJECTIVE
Non-obese patients with type 2 diabetes (T2DM) are characterized by predominant defective insulin secretion. However, in non-obese T2DM patients, metformin, targeting insulin resistance, is non-inferior to the prandial insulin secretagogue, repaglinide, controlling overall glycaemia (HbA1c). Whether the same apply for postprandial glucose and lipid metabolism is unknown. Here, we compared the effect of metformin versus repaglinide on postprandial metabolism in non-obese T2DM patients.


METHODS
Single-centre, double-masked, double-dummy, crossover study during 2x4 months involving 96 non-obese (body mass index < or = 27 kg/m2) insulin-naïve T2DM patients. At enrolment, patients stopped prior oral hypoglycaemic agents therapies and after a 1-month run-in period on diet-only treatment, patients were randomized to repaglinide (2 mg) thrice daily followed by metformin (1 g) twice daily or vice versa each during 4 months with 1-month washout between interventions.


METHODS
Postprandial metabolism was evaluated by a standard test meal (3515 kJ; 54% fat, 13% protein and 33% carbohydrate) with blood sampling 0-6 h postprandially.


RESULTS
Fasting levels and total area under the curve (AUC) for plasma glucose, triglycerides and free fatty acids (FFA) changed equally between treatments. In contrast, fasting levels and AUC of total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and serum insulin were lower during metformin than repaglinide (mean (95% confidence intervals), LDL cholesterol difference metformin versus repaglinide: AUC: -0.17 mmol/l (-0.26; -0.08)). AUC differences remained significant after adjusting for fasting levels.


CONCLUSIONS
In non-obese T2DM patients, metformin reduced postprandial levels of glycaemia, triglycerides and FFA similarly compared to the prandial insulin secretagogue, repaglinide. Furthermore, metformin reduced fasting and postprandial cholesterolaemia and insulinaemia compared with repaglinide. These data support prescription of metformin as the preferred drug in non-obese patients with T2DM targeting fasting and postprandial glucose and lipid metabolism.
Lund
Søren S
SS
Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark. sqrl@steno.dk
Tarnow
Lise
L
Frandsen
Merete
M
Smidt
Ulla M
UM
Pedersen
Oluf
O
Parving
Hans-Henrik
HH
Vaag
Allan A
AA
D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D002219:Carbamates / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002219:Carbamates; D008078:Cholesterol, LDL; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D010880:Piperidines; D014280:Triglycerides; C072379:repaglinide; D008687:Metformin; D002784:Cholesterol