LONG-TERM EFFECTS OF FLUOXETINE ON GLYCEMIC CONTROL IN OBESE PATIENTSWITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS OR GLUCOSE-INTOLERANCE -INFLUENCE ON MUSCLE GLYCOGEN-SYNTHASE AND INSULIN-RECEPTOR KINASE-ACTIVITY

Fluoxetine (F) is a specific serotonin-reuptake inhibitor that has bee n shown to promote weight loss and improve glycemic control in obese d iabetic patients. To study its long-term metabolic effect, 40 obese pa tients with non-insulin-dependent diabetes mellitus (NIDDM) or impaire d glucose tolerance (IGT) were included in a 19-month, randomized, pla cebo-controlled study. Patients were assigned to receive either 60 mg F or placebo (P) daily in conjunction with a 5.0-MJ/d diet (> 50% carb ohydrate). Both groups showed a significant weight loss, with a nadir after 6 months without group differences (mean +/- SD: F, 10.1 +/- 10. 0 kg; P, 9.4 +/- 11.5 kg). Fifteen patients from the F group and 14 fr om the P group completed the 12-month study without weight loss differ ences. Glycemic regulation improved along with the weight loss, but wi th a larger decline in plasma C-peptide and fasting glucose levels in the F group (P <.05). Total skeletal muscle glycogen synthase (GS) act ivity increased by 31% in the F group (P <.01) and by 17% in the P gro up (nonsignificant) after 6 months of treatment, but was still less th an the activity in normal-weight controls (aged 28.0 +/- 6.3 years; bo dy mass index, 23.5 +/- 2.2). After adjustment for fasting glucose, in sulin, weight loss, and diabetic state, a positive effect of F remaine d on the total GS activity, which accounted for 27% of the variation ( P <.05). The waist to hip ratio was reduced in P subjects as compared with F subjects (P <.05). Fat-free mass (FFM) tended to be more reduce d in the F group as compared with P subjects (4.9 v 1.9 kg), although the difference did not reach statistical significance. In conclusion, F seems to improve insulin sensitivity beyond the effect mediated thro ugh weight loss by a possible effect on GS activity in skeletal muscle tissue. Copyright (C) 1995 by W.B. Saunders Company