Intervention: Insulin tregopil
Trial phase: Phase 2 | Phase 3
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Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 31
Group description: At randomization, all subjects started on 45 mg mealtime insulin Tregopil (oral) in combination with insulin glargine (basal insulin, SC, once or twice daily) and metformin (oral) in a basal-bolus regimen. Insulin Tregopil was administered (oral) 10 minutes prior to each main meal, was titrated to the 2-hour PPG target of 141-179 mg/dL according to the titration algorithm. Dose adjustments were considered once/twice weekly in the initial 4 weeks, based on the 2-hour SMPG on the previous week. Basal insulin and metformin treatment continued without changing the frequency or dose.
Eligibility criteria:
Key Inclusion Criteria

Patients with an established diagnosis of T2DM and a duration of diabetes mellitus of at least 6 months at Screening based on criteria given below as per American Diabetes Association (ADA) 2017 guidelines: i. HbA1c ≥ 6.5% OR ii. FPG ≥ 126 mg/dL. (Fasting is defined as no caloric intake for at least 8 hours.) OR iii. 2-hour prandial glucose (PG) level of ≥ 200 mg/dL during an oral glucose tolerance test (OGTT).
Stable dose of metformin (at least 1500 mg daily [daily dose of at least 1000 mg is permitted if intolerant to 1500 mg dose]) for a period of at least 3 months prior to Screening
Eligible for initiation of or already receiving insulin glargine
Hemoglobin ≥ 10.0 g/Dl
HbA1c of 7.5% to 10.0 %
Body mass index of 18.5 to 35.0 kg/m2

Key Exclusion Criteria

Patients with T1DM
Treatment with glucagon-like peptide 1 agonists within 12 weeks prior to Screening
Ongoing treatment with OADs (eg, Thiazolidinediones) contraindicated or unapproved for combination treatment with insulin
Presence of gastrointestinal (GI) disorders or conditions known to significantly alter the absorption of orally administered drugs or significantly alter upper GI or pancreatic function
History of ≥2 episodes of severe hypoglycemia (as per ADA 2017) within the 6 months before Screening
History of > 1 episode of hyperglycemic hyperosmolar coma or hospitalization for uncontrolled diabetes (eg, diabetic ketoacidosis); within the 6 months prior to Screening
Clinically significant cardiovascular and/or cerebrovascular disease within 12 months before Screening including, but not limited to unstable angina, myocardial infarction, Class III or Class IV congestive heart failure according to the New York Heart Association criteria, valvular heart disease, cardiac arrhythmia requiring treatment, pulmonary hypertension, cardiac surgery, coronary angioplasty, stroke or transient ischemic attack.

Patients with the following secondary complications of diabetes:

i. Active proliferative retinopathy as confirmed by a dilated ophthalmoscopy (by the investigator, site ophthalmologist or an optometrist; as per standard site practice) within 6 months prior to Screening. ii. Renal dysfunction indicated by modification of diet in renal disease estimated glomerular filtration rate < 45 mL/min/1.73 m2 and/or diabetic nephropathy and/or clinical nephrotic syndrome at Screening. iii. History or presence of severe form of neuropathy or signs and symptoms of severe cardiac autonomic neuropathy. iv. Patients with non-traumatic amputation (at any time) or clinically significant