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CLINICAL STUDIES |
1 Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark2 Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark3 Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark and 4 Department of Endocrinology, University of Lund, S-20502 Malmö, Sweden
(Correspondence should be addressed to S S Lund; Email: sqrl{at}steno.dk)
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.
Design: Single-centre, double-masked, double-dummy, crossover study during 2x4 months involving 96 non-obese (body mass index
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.
This article has been cited by other articles:
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  B. Hemmingsen, S. S Lund, J. Wetterslev, and A. Vaag Oral hypoglycaemic agents, insulin resistance and cardiovascular disease in patients with type 2 diabetes Eur. J. Endocrinol., July 1, 2009; 161(1): 1 - 9. [Abstract] [Full Text] [PDF]
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S. S Lund, L. Tarnow, C. D A Stehouwer, C. G Schalkwijk, T. Teerlink, J. Gram, K. Winther, M. Frandsen, U. M Smidt, O. Pedersen, et al. Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes Eur. J. Endocrinol., May 1, 2008; 158(5): 631 - 641. [Abstract] [Full Text] [PDF]
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