The effects of miglitol on glucagon‐like peptide‐1 secretion and appetite sensations in obese type 2 diabetics
Authors: Lee A. , Patrick P. , Wishart J. , Horowitz M. , Morley J. E. 
Published: March 2003

Background:Previous studies reported that administration of first generation α‐glucosidase inhibitors (AGIs), such as voglibose or acarbose, produced exaggerated and sustained postprandial responses of glucagon‐like peptide‐1 (GLP‐1), an incretin hormone from the enteroinsular axis, in healthy humans. Little is known about the postprandial release of GLP‐1 after AGI therapy in diabetics. GLP‐1 plays a role to mediate satiety. Any agent that substantially elevates GLP‐1 levels may theoretically reduce hunger, increase satiation and limit food intake.

Objectives:This study was performed to analyse the effect of miglitol, a more potent second generation AGI with fewer gastrointestinal side‐effects, on the regulation of meal‐related GLP‐1 secretion and on the change of insulin–glucose dynamics as well as the release of gastric inhibitory polypeptide (GIP), another incretin hormone, after stimulation by an ordinary meal in obese type‐2‐diabetic subjects. Miglitol's subsequent influences on appetite sensations and food intake were also measured.

Design:In total, 8 obese type‐2‐diabetic women were randomized to receive treatment with 100 mg of miglitol or placebo three times a day for 2 days (six doses total) in a double‐blind fashion. On day 3 of each treatment period (miglitol or placebo), measurements of GLP‐1, GIP, insulin and glucose were taken periodically during 3 h after eating a 720 kcal breakfast. Appetite ratings with visual analogue scales (VASs) were used to assess ingestive behaviour hourly just before breakfast and hourly after for 6 h until immediately before lunch. The number of tuna sandwiches eaten at lunch was used to measure food consumption.

Results:The plasma GLP‐1, glucose, insulin and GIP levels in response to the mixed meal were compared after the miglitol and placebo treatment. Miglitol effectively enhanced postprandial GLP‐1 release and suppressed plasma GIP secretion. The ingestion of a mixed meal induced a remarkable rise in GLP‐1 after miglitol as compared with placebo in overweight diabetic subjects. The meal‐related rise in GLP‐1 after miglitol was significantly greater at all time‐points between 30 and 180 min than after the placebo. The postprandial incremental area under the curve for GLP‐1 with miglitol treatment was about twofold that with the placebo. The GLP‐1 level reached a maximum at 120 min after the mixed meal and steadily rose throughout the rest of the 3‐h study period. In the miglitol‐treated condition, the average caloric intake at lunch during a 30‐min eating period was 12% lower (p < 0.05) as compared with that after the placebo in six out of the eight subjects who exhibited a GLP‐1 rise after the breakfast meal by greater than 30% from the placebo‐treated condition. Correspondingly, the average rating scores were significantly lower for hunger feelings and markedly greater for sensations of satiety under the miglitol treatment; beginning 2 and 3 h, respectively, before the lunch test.

Conclusions:Miglitol induced an enhanced and prolonged GLP‐1 release at high physiological concentrations after ingesting an ordinary meal in glycaemic‐controlled diabetics. The excessive postprandial GLP‐1 elevation after miglitol therapy modified feeding behaviour and food intake, and thereby has potential value in regulating appetite and stabilizing body weight in obese type‐2‐diabetic patients.