Disease modifying therapies aiming to preserveβ-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking.Here,we conducted a multi-centre,randomized,controlled trial to assess theβ-cell pres...Disease modifying therapies aiming to preserveβ-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking.Here,we conducted a multi-centre,randomized,controlled trial to assess theβ-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 diabetes.In this 3-arm trial,301 participants were randomly assigned to a 24-month course of the conventional therapy(metformin with or without insulin)or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional therapy.The primary endpoint was the change from baseline to 24 months in the fasting C-peptide.The secondary endpoints included the area under the concentration-time curve(AUC)for C-peptide level in a 2-h mixed-meal tolerance test,glycemic control,total daily insulin use and safety,respectively.The primary endpoint was not achieved in saxagliptin plus vitamin D group(P=0.18)and saxagliptin group(P=0.26).However,compared with the conventional therapy,2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D(-276 pmol/L vs.-419 pmol/L;P=0.01),and not to the same degree with saxagliptin alone(-314 pmol/L;P=0.14).Notably,for participants with higher glutamic acid decarboxylase antibody(GADA)levels,the decline ofβ-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group(P=0.001).Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic control.In conclusion,the combination of saxagliptin and vitamin D preserves pancreaticβ-cell function in adult-onset autoimmune type 1 diabetes,an effect especially efficacious in individuals with higher GADA levels.Our results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes.(ClinicalTrials.gov identifier:NCT02407899).展开更多
文摘Disease modifying therapies aiming to preserveβ-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking.Here,we conducted a multi-centre,randomized,controlled trial to assess theβ-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 diabetes.In this 3-arm trial,301 participants were randomly assigned to a 24-month course of the conventional therapy(metformin with or without insulin)or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional therapy.The primary endpoint was the change from baseline to 24 months in the fasting C-peptide.The secondary endpoints included the area under the concentration-time curve(AUC)for C-peptide level in a 2-h mixed-meal tolerance test,glycemic control,total daily insulin use and safety,respectively.The primary endpoint was not achieved in saxagliptin plus vitamin D group(P=0.18)and saxagliptin group(P=0.26).However,compared with the conventional therapy,2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D(-276 pmol/L vs.-419 pmol/L;P=0.01),and not to the same degree with saxagliptin alone(-314 pmol/L;P=0.14).Notably,for participants with higher glutamic acid decarboxylase antibody(GADA)levels,the decline ofβ-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group(P=0.001).Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic control.In conclusion,the combination of saxagliptin and vitamin D preserves pancreaticβ-cell function in adult-onset autoimmune type 1 diabetes,an effect especially efficacious in individuals with higher GADA levels.Our results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes.(ClinicalTrials.gov identifier:NCT02407899).
