Oral insulin (ORMD‐0801) in type 2 diabetes mellitus: A dose‐finding 12‐week randomized placebo‐controlled study. Issue 4 (21st November 2022)

• Record Type: Journal Article
• Authors: Eldor, Roy; Francis, Bruce H.; Fleming, Alexander; Neutel, Joel; Homer, Kenneth; Kidron, Miriam; Rosenstock, Julio
• Is Part Of: Diabetes, obesity & metabolism. Volume 25:Issue 4(2023)
• Page Start: 943
• Page End: 952
• Publication Date: 2022-11-21
• Subjects: clinical trial -- cohort study -- continuous glucose monitoring (CGM) -- insulin therapy -- type 2 diabetes; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.14901
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract: Aims: To assess the safety and efficacy of multiple daily doses of oral insulin (ORMD‐0801) in subjects with type 2 diabetes (T2DM) over 12 weeks. Materials and Methods: Participants with T2DM on metformin or combination oral therapy with glycated haemoglobin (HbA1c) levels ≥ 7.5% (58 mmol/mol) were randomized to receive ORMD‐0801 8 mg or 16 mg once (QD) or twice (BID) daily, or 32 mg QD, BID or three times daily (TID) over a 12‐week period. Results: A total of 373 subjects were randomized to active treatment or placebo (~60% male, age ~ 56 years, HbA1c 9%‐9.8%; 75‐84 mmol/mol). Placebo‐adjusted HbA1c changes from baseline to Week 12 were observed with ORMD‐0801 8 mg BID (−7.15 ± 3.57 mmol/mol [−0.65% ± 0.33%]; P = 0.046). However, a significant site interaction was observed in two sites. After excluding these, HbA1c reduction was observed with 8 mg QD (−0.81 ± 0.37%; −8.89 ± 4.01 mmol/mol; P = 0.028, n = 15), 8 mg BID (−0.82 ± 0.37%; −8.95 ± 4.08 mmol/mol; P = 0.029, n = 17), 32 mg QD (−0.54 ± 0.26%; −5.89 ± 2.78 mmol/mol; P = 0.036, n = 69) and 32 mg BID (−0.53 ± 0.26%; −5.80 ± 2.83 mmol/mol; P = 0.042, n = 68). No effect was observed with 16 mg QD (0.25 ± 0.37%; 2.76 ± 3.99 mmol/mol; P = 0.48, n = 18), 16 mg BID (−0.36 ± 0.40%; −3.97 ± P = 0.36, n = 15) or 32 mg TID (−0.45 ± 0.27%, −4.89 ± 2.90 mmol/mol; P = 0.093, n = 69). Continuous glucose monitor and serum glucose measurements showed similar trends but were not significant. ORMD‐0801 was safe, well tolerated and not associated with weight gain or hypoglycaemia. Conclusions: Oral insulin (ORMD‐0801) induced greater reductions in HbA1c when compared to placebo, and was safe and well tolerated in individuals with uncontrolled T2DM. The efficacy and safety findings support continued development of the 8‐mg dose at bedtime, which is currently being evaluated in two Phase 3 trials.