title: Targeting hyperglycaemia with either metformin or repaglinide in non-obese patients with type 2 diabetes: results from a randomized crossover trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Steno Diabetes Center, Gentofte, Denmark. sqrl@steno.dk
authors: S S
authors: SS
authors: Lund
authors: L
authors: L
authors: Tarnow
authors: C D A
authors: CD
authors: Stehouwer
authors: C G
authors: CG
authors: Schalkwijk
authors: M
authors: M
authors: Frandsen
authors: U M
authors: UM
authors: Smidt
authors: O
authors: O
authors: Pedersen
authors: H-H
authors: HH
authors: Parving
authors: A
authors: A
authors: Vaag
mesh_terms: D052242:Adiponectin / Q000097:blood; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010349:Patient Compliance; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D049629:Waist-Hip Ratio
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D002097:C-Reactive Protein; D002219:Carbamates; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D010880:Piperidines; C072379:repaglinide