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- Title
Possible Long-Term Efficacy of Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, for Slowly Progressive Type 1 Diabetes (SPIDDM) in the Stage of Non-Insulin-Dependency: An Open-Label Randomized Controlled Pilot Trial (SPAN-S).
- Authors
Takuya Awata; Akira Shimada; Taro Maruyama; Yoichi Oikawa; Nobuyuki Yasukawa; Susumu Kurihara; Yumi Miyashita; Masako Hatano; Yuichi Ikegami; Masafumi Matsuda; Masataka Niwa; Youichiro Kazama; Shoichiro Tanaka; Tetsuro Kobayashi
- Abstract
Introduction: We tested the hypothesis that dipeptidyl peptidase-4 (DPP-4) inhibitors are effective in preserving the b-cell function for long-term periods in patients with slowly progressive type 1 diabetes (SPIDDM) or latent autoimmune diabetes in adults (LADA). Methods: In the present open-label, randomized, controlled trial, 14 non-insulin-requiring diabetic patients with glutamic acid decarboxylase autoantibodies (GADAb) were randomly assigned to receive either sitagliptin (S group) or pioglitazone (P group). As a historical control, the Tokyo Study, in which non-insulin- dependent patients with SPIDDM were assigned to receive treatment by either insulin or sulfonylurea (SU), was used. Results: On average, the ΣC-peptide values during the oral glucose tolerance test through the follow-up periods showed a nonsignificant increase in the S group (n = 6, n =5 at 48 months) compared to the P group (n = 5, n = 2 at 48 months). In comparison to the data in the Tokyo Study, treatment by sitagliptin significantly influenced the longitudinal changes in the ΣC-peptide values with a more increased direction than insulin or SU, especially in patients with 48 months of follow-up (p = 0.014 and p = 0.007, respectively). Although the titers of GADAb were not significantly different between the S and P groups during the study, the change ratio of the GADAb titers from baseline was significantly inversely correlated with the change ratio of the ΣC-peptide values from baseline in the S group (p = 0.003); in particular, when the GADAb titers decreased from baseline, the ΣC-peptide values frequently increased. Conclusion: The present pilot trial suggests that treatment of SPIDDM/LADA by sitagliptin, a DPP-4 inhibitor, may be more effective in preserving the b-cell function than insulin treatment for at least 4 years, possibly through the immune modulatory effects of DPP-4 inhibitors.
- Subjects
SITAGLIPTIN; DRUG efficacy; CD26 antigen; B cells; TYPE 1 diabetes; HYPOGLYCEMIC agents; PHARMACODYNAMICS; TREATMENT of diabetes
- Publication
Diabetes Therapy, 2017, Vol 8, Issue 5, p1123
- ISSN
1869-6953
- Publication type
Article
- DOI
10.1007/s13300-017-0299-7