R Buzzetti1, P Pozzilli2,3, R Frederich4, N Iqbal4, B Hirshberg5. 1. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. 2. Department of Endocrinology and Diabetes, Università Campus Bio-Medico, Rome, Italy. 3. Centre for Immunology, St. Bartholomew's Hospital and the London School of Medicine, Queen Mary, University of London, London, UK. 4. Bristol-Myers Squibb, Princeton, NJ, USA. 5. MedImmune, Gaithersburg, MD, USA.
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. 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.
RCT Entities:
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.
Authors: Raffaella Buzzetti; Ernesto Maddaloni; Jason Gaglia; R David Leslie; F Susan Wong; Bernhard O Boehm Journal: Nat Rev Dis Primers Date: 2022-09-22 Impact factor: 65.038
Authors: Giovanni Mario Pes; Alessandro Palmerio Delitala; Alessandra Errigo; Giuseppe Delitala; Maria Pina Dore Journal: Intern Emerg Med Date: 2015-11-26 Impact factor: 3.397
Authors: Juan Huang; James Alexander Pearson; F Susan Wong; Li Wen; Zhiguang Zhou Journal: Diabetes Metab Res Rev Date: 2021-06-22 Impact factor: 4.876
Authors: E Rapti; S Karras; M Grammatiki; A Mousiolis; X Tsekmekidou; E Potolidis; P Zebekakis; M Daniilidis; K Kotsa Journal: Endocrinol Diabetes Metab Case Rep Date: 2016-05-27