Saxagliptin improves glycaemic control and C-peptide secretion in latent autoimmune diabetes in adults (LADA)

Diabetes Metab Res Rev. 2016 Mar;32(3):289-96. doi: 10.1002/dmrr.2717. Epub 2015 Oct 28.


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.

Conclusion: 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.

Keywords: C-peptide; dipeptidyl peptidase-4 inhibitor; glutamic acid decarboxylase antibody; latent autoimmune diabetes in adults; saxagliptin.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Adolescent
  • Adult
  • Aged
  • Blood Glucose / metabolism
  • C-Peptide / metabolism*
  • Dipeptides / therapeutic use*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Female
  • Glucose Intolerance / prevention & control*
  • Humans
  • Latent Autoimmune Diabetes in Adults / drug therapy*
  • Latent Autoimmune Diabetes in Adults / metabolism
  • Latent Autoimmune Diabetes in Adults / pathology
  • Male
  • Middle Aged
  • Young Adult


  • Blood Glucose
  • C-Peptide
  • Dipeptides
  • Dipeptidyl-Peptidase IV Inhibitors
  • saxagliptin
  • Adamantane