title: Saxagliptin improves glycaemic control and C-peptide secretion in latent autoimmune diabetes in adults (LADA).
abstract: BACKGROUND
  To assess the efficacy and tolerability of saxagliptin and C-peptide secretion in patients with diagnosed type 2 diabetes classified as glutamic acid decarboxylase antibody (GADA)-positive or GADA-negative.
  
  
  METHODS
  Post hoc analysis of data pooled from five randomized, placebo-controlled, 24-week phase 3 studies (n = 2709) was conducted. We evaluated mean change from baseline at week 24 in HbA1c , fasting plasma glucose, postprandial plasma glucose, fasting and postprandial C-peptide, and HOMA2-%β and the proportion of patients achieving HbA1c  < 7% (53 mmol/mol) at week 24.
  
  
  RESULTS
  Saxagliptin produced greater adjusted mean reductions from baseline in HbA1c versus placebo for GADA-negative [difference vs placebo (95% CI), -0.62% (-0.71% to -0.54%); -6.8 mmol/mol (-7.8, -5.9)] and GADA-positive patients [-0.64% (-1.01% to -0.27%); -7.0 mmol/mol (-11.0, -3.0)]. Consistently, saxagliptin produced a greater reduction from baseline in fasting plasma glucose and postprandial plasma glucose versus placebo in GADA-positive versus GADA-negative patients, and more patients achieved HbA1c  < 7% (53 mmol/mol) with saxagliptin versus placebo in both GADA-negative and GADA-positive patients. Saxagliptin increased β-cell function as assessed by HOMA2-%β and postprandial C-peptide area under the curve from baseline in patients in both GADA-positive and GADA-negative patients. Adverse events and hypoglycaemic events were similar across treatment groups and GADA categories.
  
  
  CONCLUSIONS
  Saxagliptin was effective in lowering blood glucose levels and generally well tolerated in GADA-positive patients. Interestingly, saxagliptin appears to improve β-cell function in these patients, although a longer treatment duration may be needed to confirm this finding.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Buzzetti
authors.affiliation: Department of Endocrinology and Diabetes, Università Campus Bio-Medico, Rome, Italy.|Centre for Immunology, St. Bartholomew's Hospital and the London School of Medicine, Queen Mary, University of London, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Pozzilli
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: R
authors.initials: R
authors.lastname: Frederich
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: N
authors.initials: N
authors.lastname: Iqbal
authors.affiliation: MedImmune, Gaithersburg, MD, USA.
authors.forename: B
authors.initials: B
authors.lastname: Hirshberg
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism*; D004151:Dipeptides / Q000627:therapeutic use*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D018149:Glucose Intolerance / Q000517:prevention & control*; D006801:Humans; D000071698:Latent Autoimmune Diabetes in Adults / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; C502994:saxagliptin; D000218:Adamantane
keywords: C-peptide; dipeptidyl peptidase-4 inhibitor; glutamic acid decarboxylase antibody; latent autoimmune diabetes in adults; saxagliptin