The EFFECT OF TWO NEW Α‐GLUCOSIDASE INHIBITORS ON METABOLIC RESPONSES TO a MIXED MEAL IN NORMAL VOLUNTEERS

Abstract

1. alpha-Glucosidase inhibitors delay carbohydrate absorption and have been proposed as adjunctive therapy for diabetes mellitus. 2. To determine the effects of two new alpha-glucosidase inhibitors, Bay-m-1099 and Bay-o-1248, on meal carbohydrate and lipid tolerance, plasma glucose, insulin and triglyceride levels were measured at 15-60 min intervals over 12 h after ingestion of a standard breakfast, lunch and dinner of identical composition in 31 normal volunteers. 3. The volunteers were randomized to receive either Bay-m-1099 (50 or 25 mg) or placebo prior to each meal, or the single administration of Bay-o-1248 (20 or 10 mg) or placebo prior to breakfast. 4. Only Bay-m-1099 at the 50 mg dose reduced significantly the postprandial increase in plasma insulin levels after each meal when compared with placebo (25, 36, 54% at breakfast, lunch, and dinner, respectively; P less than 0.05). Both drugs were well tolerated, with side effects limited to complaints of flatulence. 5. Thus, with the dosage schedule employed, Bay-m-1099, but not Bay-o-1248, significantly reduced postprandial increments in plasma insulin.

Effects of alpha-glucosidase-inhibiting drugs on acute postprandial glucose and insulin responses: a systematic review and meta-analysis

“…In meta-analyses of longerterm studies with acarbose in diabetes, there was no dosedependent effect seen on HbA1c 17,19 , but there was for post-load glucose 17 . The observed dose-response effect for miglitol on PPG is in line with the within-study comparisons in underlying studies, most though not all of which indicate dose-dependent effects of miglitol on PPG [36][37][38][39] . Moreover, longer-term studies, although scarce, have been suggestive of a dose-response effect of miglitol on HbA1c 17 .…”

Modification of energy density with inhibitors of carbohydrate and fat digestion

“…Over 12 h during which standard mixed meals were taken by healthy volunteers after a single dose of either 10 or 20 mg emiglitate, there was no significant effect on post-prandial insulin, glucose or triacylglycerol responses compared with placebo. The higher dose caused significantly more adverse effects than placebo (Kennedy et al 1987). However, in a second study in healthy subjects emiglitate reduced post-prandial glucose and insulin rises acutely but had no effect on triacylglycerol levels (Hillebrand et al 1986).…”

Are postprandial triglyceride and insulin abnormalities neglected cardiovascular risk factors in type 2 diabetes?

“…Type 2 diabetes is a long‐term disease, which requires a safe and easy‐to‐use drug that is effective at reducing postprandial blood glucose levels. Miglitol, due to its mode of action, is the treatment of choice for patients insufficiently controlled with diet alone (monotherapy), without causing a hyperinsulinaemia, and can be used in combination therapy [44–47,54].…”

“…It is well documented that the α‐glucosidase inhibitors, such as miglitol, are effective in reducing postprandial hyperglycaemia [41–43]. It also has the potential to improve insulin sensitivity, by reducing postprandial hyperinsulinaemia, without weight gain and without the risk of hypoglycaemia [44–47]. As well as effectively controlling postprandial hyperglycaemia, α‐glucosidase inhibitors have been shown to have beneficial effects on serum lipids in type 2 diabetic patients by reducing both fasting triglyceride levels [44] and postprandial hypertriglyceridaemia [48].…”