Initial phase II clinical studies on midaglizole (DG-5128): a new hypoglycemic agent
S Kawazu, M Suzuki, K Negishi, J Ishii, H Sando… - Diabetes, 1987 - Am Diabetes Assoc
S Kawazu, M Suzuki, K Negishi, J Ishii, H Sando, H Katagiri, Y Kanazawa, S Yamanouchi…
Diabetes, 1987•Am Diabetes AssocMidaglizole (DG-5128), 2-[2-(4, 5-dihydro-1 H-imidazol-2-yl)-1-phenylethyl] pyridine
dihydrochloride sesquihydrate, is a new type of oral antidiabetic agent that has an α2-
adrenoceptor-antagonizing effect. As previously reported, midaglizole reduces plasma
glucose, mainly by stimulation of insulin secretion, and inhibits epinephrine-induced platelet
aggregation in normal human subjects. In this study, the clinical safety and efficacy of
shortterm administration of midaglizole were evaluated in 47 patients with non-insulin …
dihydrochloride sesquihydrate, is a new type of oral antidiabetic agent that has an α2-
adrenoceptor-antagonizing effect. As previously reported, midaglizole reduces plasma
glucose, mainly by stimulation of insulin secretion, and inhibits epinephrine-induced platelet
aggregation in normal human subjects. In this study, the clinical safety and efficacy of
shortterm administration of midaglizole were evaluated in 47 patients with non-insulin …
Midaglizole (DG-5128), 2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenylethyl]pyridine dihydrochloride sesquihydrate, is a new type of oral antidiabetic agent that has an α2-adrenoceptor-antagonizing effect. As previously reported, midaglizole reduces plasma glucose, mainly by stimulation of insulin secretion, and inhibits epinephrine-induced platelet aggregation in normal human subjects.
In this study, the clinical safety and efficacy of shortterm administration of midaglizole were evaluated in 47 patients with non-insulin-dependent diabetes mellitus (NIDDM). After an observation period on diet or sulfonylurea treatment (1 patient was on insulin), patients received 150–250 mg 3 times a day of midaglizole for 2–4 wk, (some patients continued treatment for >4 wk).
In 20 of the patients first treated with diet and then switched to midaglizole treatment, fasting plasma glucose (FPG) decreased significantly from 187 ± 10 mg/ dl (mean ± SE) to 147 ± 13 mg/dl (P < .05) and 120 ± 6 mg/dl (P < .01) 2 and 4 wk, respectively, after administration of midaglizole. Glycosylated hemoglobin (HbA1 also decreased from 12.0 ± 0.7 to 11.3 ± 1.1 and 10.7 ± 0.6% after 2 and 4 wk, respectively. In 23 of the patients whose treatment was changed from sulfonylureas to midaglizole, FPG, and HbA1 levels were maintained at the same values obtained before administration of midaglizole. In patients treated with midaglizole for >12 wk, FPG and HbA1 were kept at the lowered levels.
Moreover, midaglizole treatment showed a clear inhibitory effect on postprandial hyperglycemia and onFPG, reflecting the general improvement in the daily plasma glucose curve with significantly reduced fluctuation. In the oral glucose tolerance test, midaglizole significantly improved glucose tolerance, potentiated insulin secretion, and tended to depress glucagon secretion.
No abnormal findings attributable to midaglizole were noted in clinical and laboratory examinations, except for diarrhea and soft stools in 4 cases (8.5%) out of 47. No hypoglycemic symptoms were observed in this trial.
Thus, midaglizole is clinically effective for NIDDM because it improves the daily plasma gluocse curve, with decreased fasting and postprandial hyperglycemia, in addition to amelioration of oral glucose tolerance accompanied by accelerated insulin secretion.
Am Diabetes Assoc