Targeting hyperglycaemia with either metformin or repaglinide in non-obese patients with type 2 diabetes: results from a randomized crossover trial

Aarhus University, Aarhus, Central Jutland, Denmark
Diabetes Obesity and Metabolism (Impact Factor: 5.46). 05/2007; 9(3):394-407. DOI: 10.1111/j.1463-1326.2007.00713.x
Source: PubMed

ABSTRACT Metformin is the 'drug-of-first-choice' in obese patients with type 2 diabetes mellitus (T2DM) due to its antihyperglycaemic and cardiovascular protective potentials. In non-obese patients with T2DM, insulin secretagogues are empirically used as first choice. In this investigator-initiated trial, we evaluated the effect of metformin vs. an insulin secretagogue, repaglinide on glycaemic regulation and markers of inflammation and insulin sensitivity in non-obese patients with T2DM.
A single-centre, double-masked, double-dummy, crossover study during 2 x 4 months involved 96 non-obese (body mass index < or = 27 kg/m(2)) insulin-naïve patients with T2DM. At enrolment, previous oral hypoglycaemic agents (OHA) were stopped and patients entered a 1-month run-in on diet-only treatment. Hereafter, patients were randomized to either 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.
End-of-treatment levels of haemoglobin A(1c) (HbA(1c)), fasting plasma glucose, mean of seven-point home-monitored plasma glucose and fasting levels of high-sensitivity C-reactive protein and adiponectin were not significantly different between treatments. However, body weight, waist circumference, fasting serum levels of insulin and C-peptide were lower and less number of patients experienced hypoglycaemia during treatment with metformin vs. repaglinide. Both drugs were well tolerated.
In non-obese patients with T2DM, overall glycaemic regulation was equivalent with less hypoglycaemia during metformin vs. repaglinide treatment for 2 x 4 months. Metformin was more effective targeting non-glycaemic cardiovascular risk markers related to total and abdominal body fat stores as well as fasting insulinaemia. These findings may suggest the use of metformin as the preferred OHA also in non-obese patients with T2DM.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetes mellitus is a progressive disorder of glucose metabolism. It is estimated that about 285 million people between the ages of 20 and 79 years had diabetes worldwide in 2010, or 5% of the adult population. Type 2 diabetes may occur with obesity, hypertension, and dyslipidaemia (the metabolic syndrome), which are powerful predictors of cardiovascular disease. Without adequate blood-glucose-lowering treatment, blood glucose levels may rise progressively over time in people with type 2 diabetes. Microvascular and macrovascular complications may develop. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of blood-glucose-lowering medications in adults with type 2 diabetes? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 194 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: alpha-glucosidase inhibitors (AGIs), combination treatment (single, double, and triple), dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues, insulins (including conventional [human] and analogue, different regimens, different length of action), meglitinides, metformin, sulphonylureas, and thiazolidinediones.
    Clinical evidence 01/2012; 2012.
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present work was to test the ability of two non-diabetogenic carbohydrates to intranasally deliver the insulinotropic drug repaglinide (REP) for controlling blood glucose level. REP was loaded onto chitosan/alginate nanocomplexes (NCs) suitable for mucosal delivery and uptake. Improved stability and delivery characteristics were obtained by spray drying the selected NCs, yielding microparticles. A statistical experimental design was adopted to investigate the effects of the formulations' variables on two critical responses: NC size and drug entrapment efficiency. Physicochemical characterizations of the network's structures were done, and in vitro cytotoxicity and histopathological studies were conducted. The potential of the developed system to prolong the drug effect was tested on diabetic rats. The results showed that to attain particles suitable for nasal delivery, alginate should be used at its lowest level used in this study (0.6 mg/mL). A low level of chitosan (0.5 mg/mL) was needed when the drug was cation-loaded, while the high chitosan level (1 mg/mL) was more suitable when REP was anion-loaded. The best entrapment efficiency was achieved at a theoretical drug loading of 0.025 mg/mL. Discrete NCs could be rapidly recovered from the spray-dried microparticles. The cytotoxicity and histopathological studies indicated that such formulations were well tolerated. The antihyperglycemic activity of the nasally administered formulae was gradual but was significantly sustained over 24 hours, suggesting NC mucosal uptake. Nasal delivery of such dry powders achieved better glycemic control compared with the conventional oral tablets.
    International Journal of Nanomedicine 01/2014; 9:4449-4465. DOI:10.2147/IJN.S66876 · 4.20 Impact Factor