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)

• Published in: Diabetes therapy 2017-10, Vol.8 (5), p.1123-1134
• Main Authors: Awata, Takuya, Shimada, Akira, Maruyama, Taro, Oikawa, Yoichi, Yasukawa, Nobuyuki, Kurihara, Susumu, Miyashita, Yumi, Hatano, Masako, Ikegami, Yuichi, Matsuda, Masafumi, Niwa, Masataka, Kazama, Youichiro, Tanaka, Shoichiro, Kobayashi, Tetsuro
• Format: Article
• Language: English
• Subjects: Cardiology; Clinical outcomes; Clinical trials; Diabetes; Drug therapy; Endocrinology; Evidence-based medicine; Glucose; Inhibitor drugs; Insulin; Internal Medicine; Medicine; Medicine & Public Health; Original Research
• ISSN: 1869-6953; 1869-6961
• DOI: 10.1007/s13300-017-0299-7

Introduction We tested the hypothesis that dipeptidyl peptidase-4 (DPP-4) inhibitors are effective in preserving the β-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 ∑C-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 ∑C-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 ∑C-peptide values from baseline in the S group ( p  = 0.003); in particular, when the GADAb titers decreased from baseline, the ∑C-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 β-cell function than insulin treatment for at least 4 years, possibly through the immune modulatory effects of DPP-4 inhibitors. Clinical trial registration Japanese Clinical Trials Registry UMIN000003693.