Background: Islet neogenesis associated protein (INGAP) has beta cell regenerating effects in experimental models.
Methods: Subjects with T1DM (N = 63) and T2DM (N = 126) received 300 or 600 mg/day of INGAP peptide in a 90 day, randomized, double-blind, placebo-controlled trial.
Results: In T1DM, on-treatment Arginine-stimulated C-peptide (AUC(0-30)) significantly increased from baseline in the 600 mg group (p = 0.0058 versus placebo); no significant changes were seen in the 300 mg group. In T2DM, stimulated C-peptide was significantly better preserved in the 600 mg group compared to placebo at day 120, 30 days after washout (p = 0.031 versus placebo), but did not reach statistical significance during treatment or in the 300 mg group. In T2DM, A1C decreased significantly more in the 600 mg group compared to placebo at day 90 (-0.94% versus -0.47%, respectively, p = 0.009) and day 120, 30 days after washout (-0.73% versus -0.24%, respectively, p = 0.013). This was accompanied by significant reductions in mean glucose. No difference from placebo was detected in the 300 mg group or in T1DM. Injection site reactions were the most common adverse event, occurring in 8 (36%) of placebo, 19 (90%) of 300 mg, and 15 (75%) of 600 mg groups (T1DM) and 14 (33%) of placebo, 27 (64%) of 300 mg, and 29 (69%) of 600 mg groups (T2DM).
Conclusions: INGAP peptide increases C-peptide secretion in T1DM and improves glycaemic control in T2DM. Longer-term exposure, more frequent dosing, better tolerated formulations or combination with other therapies may be necessary to achieve optimal clinical response.