The
Precose Resolution of Optimal Titration to Enhance Current
Therapies (PROTECT) study is an ongoing Phase IV clinical trial designed to assess the effectiveness, tolerability, and safety of
acarbose tablets in patients with type II diabetes when the dosage is slowly titrated upward. This multicenter, open-label, 28-week trial will enroll approximately 7,000 type II diabetic patients. The present report describes the interim results for 2,139 patients who completed the trial as of November 1, 1996. Patients with type II diabetes enrolled in the study were inadequately controlled either with diet alone or with a sulfonylurea. The dosage of
acarbose was titrated from 25 mg three times a day (TID) to 100 mg TID based on tolerability and efficacy. Efficacy of
glycemic control was assessed by changes in
glycated hemoglobin A1c (
Hb A1c) and 1-hour postprandial plasma
glucose (PPG) levels. Tolerability and safety were determined by patient reports of treatment-emergent adverse events and by review of laboratory tests. The PROTECT study confirms the previously demonstrated efficacy and safety of
acarbose in improving
glycemic control in patients with type II diabetes regardless of a patient's age,
body weight, ethnic background, time since diagnosis, or severity of disease. mean 1-hour PPG levels declined throughout the entire treatment period, with a mean decrease from baseline of -47 mg/dL at the end of treatment.
Hb A1c, the most reliable
indicator of long-term
glycemic control, decreased over the course of treatment, resulting in a mean decrease of -0.7% (P < 0.001). Although all patient types enrolled in the study responded positively to
therapy, certain subgroups responded particularly well, such as those patients diagnosed with the disease less than 1 year ago, those treated with
acarbose as monotherapy, and those with higher baseline
Hb A1c levels. Adverse events were experienced by 36% of all patients and consisted primarily of gastrointestinal disturbances (
flatulence,
diarrhea,
abdominal pain). Moderate
renal insufficiency (serum
creatinine levels between 1.5 and 2 mg/dL) was present in 259 patients, and no patients developed serum hepatic
transaminase levels more than twice the normal range.