title: Eight weeks of treatment with long-acting GLP-1 analog taspoglutide improves postprandial insulin secretion and sensitivity in metformin-treated patients with type 2 diabetes.
abstract: OBJECTIVE
  Loss of pancreatic function is pivotal to the deterioration of fasting and postprandial glycemic control in type 2 diabetes (T2D). We evaluated the effects of a long-acting, human glucagon-like peptide-1 analog, taspoglutide, added to metformin, on pancreatic function and peripheral insulin sensitivity.
  
  
  METHODS
  We studied 80 T2D patients inadequately controlled [glycosylated hemoglobin (HbA1c), 7.0%-9.5%] receiving stable metformin for ≥12weeks. They were a subset of participants to a phase 2 trial that received also a 240-min mixed-meal tolerance test (MTT) at baseline and study end. Patients received once weekly (QW) sc injection of taspoglutide 5, 10, or 20mg (n=21, 19, or 19), or placebo (n=21), plus metformin, for 8weeks. We measured postprandial plasma glucose (PPG) and insulin profiles, insulin secretion rate (ISR), oral glucose insulin sensitivity (OGIS) index; β-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios, and insulin sensitivity-to-insulin resistance (or disposition) index.
  
  
  RESULTS
  After 8 weeks of treatment, taspoglutide 5, 10, and 20mg QW doses vs. placebo improved mean PPG0-240 min (relative change from baseline: -22.1%, -25.9%, and -22.9% vs. -8.1%; P<0.005) and mean postprandial ISR0-240 min (+14%, +18%, and +23% vs. +1%; P<0.005 vs dose). Taspoglutide at 20mg QW dose also resulted in improvements from baseline in OGIS, β-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios and the disposition index during the MTT.
  
  
  CONCLUSIONS
  Taspoglutide QW significantly improved pancreatic function in patients with T2D treated with metformin.
authors.affiliation: Institute of Clinical Physiology, National Research Council, Pisa, Italy. amalia@ifc.cnr.it
authors.forename: Amalia
authors.initials: A
authors.lastname: Gastaldelli
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nauck
authors.forename: Raffaella
authors.initials: R
authors.lastname: Balena
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D019518:Postprandial Period / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; C541736:taspoglutide; D008687:Metformin
keywords: AUC; BMI; FPG; GLP-1; GLP-1 analog pancreatic function; HbA(1c); ISR; MTT; Mixed-meal tolerance test; OGIS; PPG; Postprandial glucagon; Postprandial glucose; Postprandial insulin; Q2W; QW; T2D; area under the curve; body mass index; fasting plasma glucose; glucagon-like peptide 1; glycosylated hemoglobin; insulin secretion rate; mixed-meal tolerance test; once every 2weeks; once-weekly; oral-glucose insulin sensitivity; postprandial plasma glucose; type 2 diabetes