Sitagliptin plus pantoprazole can restore but not maintain insulin independence after clinical islet transplantation: results of a pilot study. Issue 2 (22nd May 2016)

• Record Type: Journal Article
• Authors: Senior, P. A.; Koh, A.; Yau, J.; Imes, S.; Dinyari, P.; Malcolm, A. J.; Light, P.; Shapiro, A. M. J.
• Is Part Of: Diabetic medicine. Volume 34:Issue 2(2017)
• Page Start: 204
• Page End: 212
• Publication Date: 2016-05-22
• Subjects: Diabetes -- Periodicals; 616.462
• DOI: 10.1111/dme.13131
• Languages: English
• ISSNs: 0742-3071

Abstract

Abstract: Aims: Resuming insulin use due to waning function is common after islet transplantation. Animal studies suggest that gastrointestinal hormones, including gastrin and incretins may increase β–cell mass. We tested the hypothesis that pantoprazole plus sitagliptin, would restore insulin independence in islet transplant recipients with early graft insufficiency and determined whether this would persist after a 3–month washout. Methods: Single‐centre, uncontrolled, open label study of sitagliptin 100 mg daily plus pantoprazole 40 mg twice daily for 6 months. Results: After 6 months of treatment, two of eight participants (25%) achieved the primary endpoint, defined as HbA1C < 42 mmol/mol (6%), fasting plasma glucose < 7.0 mmol, C–peptide > 0.5 nmol and no insulin use. There was a significant reduction in mean insulin dose, but no change in HbA1C or weight. There were no changes in the acute insulin response to arginine, the mixed meal tolerance test or blinded continuous glucose monitoring. After the washout, no participants met the primary endpoint and HbA1C increased from 45 ± 8 mmol/mol (6.3 ± 0.7%) to 51 ± 6 mmol/mol (6.8 ± 0.6%) ( P < 0.05). Two participants had mild–moderate transient gastrointestinal side effects. There were no episodes of hypoglycaemia. Conclusions: Sitagliptin plus pantoprazole is well tolerated and safe and may restore insulin independence in some islet transplant recipients with early graft insufficiency, but this was not sustained when treatment was withdrawn. A larger, controlled trial is required to confirm the effectiveness of this combination to achieve insulin independence and to confidently exclude any persistent benefit for graft function. (Clinical Trials Registry No.: NCT00768651) What's new?: Declining graft function is common after islet transplant, but there are no treatments to reverse this. We tested a combination of sitagliptin and pantoprazole in islet recipients with early graft insufficiency because gut peptides can increase β–cell mass in rodents. Islet function improved, and insulin independence re‐established in 25%, but did not persist when treatment was withdrawn. This is the first prospective study to evaluate the potential to promote preservation and/or regeneration of β–cells after clinical islet transplantation.