Sitagliptin Treatment After Total Pancreatectomy With Islet Autotransplantation: A Randomized, Placebo-Controlled Study

Abstract

Insulin independence after total pancreatectomy and islet autotransplant (TPIAT) for chronic pancreatitis is limited by a high rate of post-procedure beta cell apoptosis. Endogenous GLP-1 and GIP, which are increased by DPP-4 inhibitor therapy (sitagliptin) may protect against beta cell apoptosis. To determine the effect of sitgalitpin after TPIAT, 83 adult TPIAT recipients were randomized to receive sitagliptin (n=54) or placebo (n=29) for 12 months after TPIAT. At 12 and 18 months after TPIAT, participants were assessed for insulin independence; metabolic testing was performed with mixed meal tolerance testing (MMTT) and frequent sample intravenous glucose tolerance testing (FSIVGTT). Insulin independence did not differ between the sitagliptin and placebo groups at 12 months (42% vs 45%, p=0.82) or 18 months (36% vs 44%, p=0.48). At 12 months, insulin dose was 9.0 (SE 1.7) unit/day and 7.9 (2.2) unit/day in the sitagliptin and placebo groups respectively (p=0.67) and at 18 months 10.3 (1.9) and 7.1 (2.6) respectively (p=0.32). HbA1c levels and insulin secretory measures were similar in the two groups, as were adverse events. In conclusion, sitagliptin could be safely administered but did not improve metabolic outcomes after TPIAT.

Autologous Mesenchymal Stem Cell and Islet Cotransplantation: Safety and Efficacy

“…Fasting plasma glucose, C‐peptide, hemoglobin A1C (HbA1c), and indexes from a mixed‐meal tolerance test (MMTT) including serum C‐peptide levels evaluated glycemic control. Insulin independence was defined as no‐insulin therapy, HbA1c <6.5%, fasting blood glucose <126 mg/dl and 2 h postprandial blood glucose <180 mg/dl. Daily oral morphine equivalents and QOL as measured by the SF‐12 questionnaire were recorded.…”

Sitagliptin treatment increases GLP-1 without improving diabetes outcomes after total pancreatectomy with islet autotransplantation

“…1 The gut-derived hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) have β-cell-protective properties, in addition to potentiating insulin secretion. 4 As we previously re- We found that the AUC for GLP-1 from MMTT at 1 year was significantly higher in patients who had received sitagliptin (4358 ± 326) vs placebo (1696 ± 426) (P = .0002) ( Table 1). 3 We hypothesized that DPP-4 inhibitor therapy (sitagliptin) after TPIAT would protect against β-cell apoptosis by increasing endogenous GLP-1 and GIP.…”

“…To test this hypothesis, we performed a randomized controlled trial in which 83 adults without preexisting diabetes were treated with sitagliptin vs placebo after TPIAT. 4 As we previously reported in the American Journal of Transplantation, diabetes outcomes including insulin independence, insulin dose, C-peptide response to mixed-meal tolerance test (MMTT), and intravenous glucose were no different in sitagliptin-treated patients vs placebo-treated controls.…”

Islet cell dysfunction in patients with chronic pancreatitis

“…A randomized controlled trial did not show any difference in insulin and C-peptide response in sitagliptin treated patients with CP who underwent TP-AIT in comparison to placebo after up to 18 months of treatment[ 72 ]. There was no difference in insulin dependence or insulin dose reduction either.…”