The present investigations were performed in order to clarify the effects of
mazindol on
body weight and
insulin sensitivity in patients with
morbid obesity who had already been treated with a very-
low-calorie diet containing 480 kcal food (VLCD) with various
amino acids. We attempted to study whether a further decrease in
body weight would be achieved by the administration of
mazindol, because it is difficult to obtain sufficient and continuous reduction of
body weight after VLCD
therapy. Thirteen female severely obese subjects were 51.0 +/- 13.9 years old (25-73 years old), with a mean height of 154.7 +/- 5.6 cm (146.0-160.5 cm), mean weight of 84.5 +/- 9.4 kg (69-98 kg) and a mean body mass index (BMI) of 35.3 +/- 3.6 kg/m2 (29.2-41.0 kg/m2). Their mean
body weight decreased to 76.7 +/- 2.2 kg (net decrease: 6.3 +/- 0.9 kg) after VLCD
therapy for 2-4 weeks. Then they were treated by the administration of
mazindol with diet restriction (1000-1200 kal/day).
Mazindol administration resulted in a further
weight reduction of 2.9 +/- 0.5 kg after 4 weeks, 4.9 +/- 0.5 kg after 8 weeks and 6.9 +/- 0.9 kg after 12 weeks. Their blood pressure was not changed after
mazindol treatment. The responses of
blood glucose and
insulin levels in a 75 g oral
glucose tolerance test (OGTT) were not significantly different before and after
mazindol administration. The
blood glucose area calculated from the data obtained during OGTT for 120 min did not significantly differ before and after
mazindol administration, while the
insulin area significantly decreased after
mazindol treatment (from 98.0 +/- 12.1 before administration to 70.1 +/- 7.8). The mean M value reflecting
insulin sensitivity in the whole body determined by euglycemic
glucose clamping was increased significantly after
mazindol treatment (from 4.92 +/- 0.30 mg/kg/min to 6.36 +/- 0.43 mg/kg/min). The results demonstrated that
mazindol administration with diet restriction further reduced
body weight in the morbidly obese subjects
after treatment with VLCD, with an increase in the M value and a decrease in
insulin release. The results suggest that
mazindol is useful for reducing
body weight as well as improving
insulin sensitivity.