Efficacy and safety of 28‐day treatment with oral insulin (ORMD‐0801) in patients with type 2 diabetes: A randomized, placebo‐controlled trial

Abstract Aim To assess the safety and efficacy of oral insulin (ORMD‐0801) in patients with type 2 diabetes (T2D). Materials and Methods After a 2‐week washout of other medications, adult metformin‐treated patients with T2D were randomized to receive placebo or 16 or 24 mg ORMD‐0801, once daily, at bedtime, for 28 days. The mean change from baseline weighted mean night‐time glucose levels was determined from 2 nights of continuous glucose monitoring (CGM) recordings during the placebo run‐in and last week of treatment. Results In total, 188 patients (HbA1c: 7.82% ± 0.88% [placebo] and 8.08% ± 1.11% [pooled ORMD‐0801 group]) were enrolled. In the placebo group, mean night‐time CGM increased from baseline by 13.7 ± 26.1 mg/dL, whereas the increase was significantly smaller in the pooled ORMD‐0801 group (1.7 ± 23.5 mg/dL, P = .0120). Glycaemic control variables (24‐hour, fasting and daytime CGM glucose) also displayed smaller increases with ORMD‐0801 versus placebo. Change from baseline HbA1c was −0.01% in the pooled ORMD‐0801 group versus +0.20% in the placebo group ( P = .0149). ORMD‐0801 was well tolerated, with similar adverse event and hypoglycaemia rates as placebo. Conclusions In patients with T2D, bedtime ORMD‐0801 curbed increases in night‐time glycaemia, 24‐hour glycaemia and HbA1c, without increasing the risk of hypoglycaemia or safety events compared with the control arm.