Table 5 Clinical studies on oral insulin
From: Critical updates on oral insulin drug delivery systems for type 2 diabetes mellitus
Type of formulation | Oral insulin formulation | Clinical trial reg. no | Development phase | Efficacy endpoint | Result | Safety profile | Reference |
|---|---|---|---|---|---|---|---|
Liposomal nanoparticles | oral HDV-I | NCT0052178 | Phase II | AUC of glucose concentration–time graphs | Significant decrease for the AUC0–810 min period compared to placebo | ● No serious adverse events ● No hypoglycemic events ● 3 treatment-emergent adverse events (right and left forearm IV infiltrate, right forearm IV site tenderness) | [74] |
Incremental AUC for plasma glucose | ● Significant reduction at both 2 and 4 h post-breakfast compared to placebo ● No dose response effect | ||||||
Solid oral dosage form | NN1952 | NCT01028404 | Phase I | Area under the serum insulin concentration–time curve after a single dose | Compared to SC insulin: ● Higher insulin exposure ● Similar Tmax ● Bio-efficacy = 0.7% | ● Hyperglycemic and hypoglycemic events ● Diarrhea and hyperhidrosis possibly and probably related to NN1952 | [76] |
Area under the glucose infusion rate-time curve after a single dose | ● Maximum GIR of highest dosage (14,400 nmol) is comparable to SC insulin ● No significant difference in GIR compared to placebo | ||||||
I-338 | NCT02470039 | Phase II | Change in fasting plasma glucose (FPG) | No significant difference compared to insulin glargine (-2.4 mmol/L vs -2.6 mmol/L) | ● Similar number of adverse events ● Low incidence of hypoglycemia | ||
Change from baseline in 10-points plasma glucose profile | No significant difference compared to insulin glargine | ||||||
Change in HbA1C | No significant difference compared to insulin glargine | ||||||
ORMD-0801 | NCT02954601 | Phase IIa | Changes in glucose levels from baseline to the end of treatment | ● Greatest mean change in TDS dosing, followed by OD dosing ● Mean change in placebo is greater than BD dosing | Dose-dependent hypoglycemic events | [78] | |
NCT02496000 | Phase IIb | Mean change from baseline in weighted mean night-time glucose levels | ● Significant decrease in 16 mg group compared to placebo ● No dose-dependent response | ● 3 hyperglycemic events in 16 mg group ● Similar proportion of non-nocturnal hypoglycemic events and adverse events across all groups | [79] | ||
NCT03467932 | Phase II | Change in HbA1c from baseline to Week 12 | Significant reduction in 32 mg OD and BD dosing but not TDS | ● Dose-dependent hypoglycemic events ● All hypoglycemic events occurred in patients on sulfonylureas ● Similar number of adverse events across all groups | |||
Mean HbA1c change from baseline over time | 8 mg OD or BD dosing demonstrated greatest mean change (at 0.95%) | ||||||
NCT01889667 | Phase II | Mean night-time glucose levels | Lowest in 8 mg BD, followed by 8 mg + 16 mg and placebo | No serious adverse events | [82] | ||
Mean daytime glucose levels | Similar trend as night-time levels | ||||||
Eligen® insulin | NCT00982254 | Phase I | Plasma insulin level | Significantly higher Cmax and shorter Tmax than SC regular insulin | No adverse events | [67] | |
GIR | ● Max relative BA: 26% ● Max biopotency: 55% | ||||||
Capsulin | - | Phase II | GIR | ● Actrapid showed significantly greater Cmax and AUC0–6 h ● Increase in GIR sustained for 6 h | No hypoglycemic or hyperglycemic events | [70] | |
Plasma insulin level | Slight increase in both 150 U and 300 U Capsulin that is significantly lower than Actrapid | ||||||
Modified insulin | IN-105 | CTRI/2009/091/000479 | Phase II | Plasma glucose concentration under fed conditions | ● Significant decrease across all doses (10, 15, 20, and 30 mg) compared to placebo ● No significant differences between 15, 20, and 30 mg dose | ● 6 hypoglycemic cases and 1 case of relative hypoglycemia ● Most common adverse events: Increased serum triglyceride level ● No serious adverse events | [71] |
Plasma insulin level | Significantly proportional to dose | ||||||
HIM-2 | - | Phase II | Postprandial plasma glucose concentrations | Significant difference in glucodynamic parameters in 0.5 and 1.0 mg/kg dosing groups compared to placebo | ● No serious adverse events ● No hypoglycemic or hyperglycemic event | [73] |