title: The beneficial effect of metformin on β-cell function in non-obese Chinese subjects with newly diagnosed type 2 diabetes.
abstract: OBJECTIVE
  Studies with metformin suggest a favourable change in β-cell function over sulphonylureas in the early course of obese type 2 diabetes mellitus (T2DM), but it remains unclear whether a similar effect is observed in non-obese individuals. Here we investigated the effects of metformin or glipizide gastrointestinal therapeutics system extended-release formulation (GITS) on β-cell function in non-obese patients with newly diagnosed T2DM.
  
  
  METHODS
  A total of 160 newly diagnosed patients with fasting glucose 7.0-13.0 mmol/L and body mass index <30 kg/m(2) from five centres in China were randomized to metformin or glipizide GITS for 24 weeks. Early insulin secretion [the ratio of area under the curve (AUC) of insulin to glucose during 0-30 min (InsAUC30 /GluAUC30 )] and insulin sensitivity [Matsuda index (ISIM )] were assessed during the standard meal tolerance test before and after therapy. Plasma glucagon-like peptide-1(GLP-1) and glucagon levels were also measured.
  
  
  RESULTS
  Metformin improved InsAUC30 /GluAUC30 significantly (from 8.1 ± 0.6 pmol/mmol to 10.7 ± 0.7 pmol/mmol, p < 0.05), comparable to results with glipizide GITS. In the metformin-treated lean (body mass index < 25 kg/m(2) ) subgroup, the increase in ISIM was not significant, but the improvement in InsAUC30 /GluAUC30 was of great magnitude. Increased GLP-1 responses during meal tolerance test and decreased fasting glucagon level were observed after metformin treatment. Correlation analysis showed that the improvement of InsAUC30 /GluAUC30 was associated with the changes in HbA1c (r = -0.374, p = 0.000), ISIM (r = 0.356, p = 0.001), and ΔGLP-10-30 (r = 0.225, p = 0.02).
  
  
  CONCLUSIONS
  Metformin improved β-cell function in non-obese subjects with newly diagnosed T2DM, which was partly independent of the change in insulin sensitivity in these subjects. This study provides evidence-based data to support metformin use in non-obese patients with T2DM as the first-line agent, which can improve both insulin sensitivity and β-cell function.
authors: Department of Endocrinology, Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, China; Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China.
authors: Y
authors: Y
authors: Bi
authors: G Y
authors: GY
authors: Tong
authors: H J
authors: HJ
authors: Yang
authors: M Y
authors: MY
authors: Cai
authors: J H
authors: JH
authors: Ma
authors: J
authors: J
authors: Liang
authors: B
authors: B
authors: Xin
authors: H
authors: H
authors: Miao
authors: Z H
authors: ZH
authors: Peng
authors: D L
authors: DL
authors: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005913:Glipizide / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D008687:Metformin; D005913:Glipizide
keywords: beta cell function; glucagon; glucagon-like peptide-1; metformin; non-obese; type 2 diabetes mellitus