Randomized Placebo-Controlled Trial of Long-Term Treatment with Sibutramine in Mild to Moderate Obesity

Journal of Family Practice, June, 2001 by Ian G. Smith, Michael A. Goulder

[ILLUSTRATION OMITTED]

Dose-related reductions in mean waist and hip circumferences achieved by month 6 were maintained at month 12. In the placebo group at month 12 (LOCF), the reductions were similar for waist and hip (2.4 cm and 2.6 cm, respectively), while in the 10- and 15-mg sibutramine groups, waist reduction was greater than hip reduction (6.4 cm and 3.8 cm at 10 mg and 7.4 cm and 5.2 cm at 15 mg). The reductions on active treatment were significantly greater than with placebo (P [is less than] .05 for overall comparison). The mean reduction in waist/hip ratio at month 12 (LOCF) was significantly greater with 10 mg sibutramine (-0.04) and 15 mg sibutramine (-0.03) than with placebo (-0.01; P [is less than] .05; least significant difference, .02).

There were statistically significant changes in triglycerides compared with placebo ( 3.2%) at month 6 for the sibutramine 10- and 15-mg treatment groups (-10.8%, P [is less than] .05 and -10.0%, P [is less than] .01, respectively). Uric acid levels were also significantly reduced at month 6 for both sibutramine treatment groups (10 mg, -6.0% [P [is less than] .05] and 15 mg, -6.2% [P [is less than] 05] compared with placebo, -1.9%): Decrease in uric acid was the only laboratory-reported variable that was statistically significantly greater in the sibutramine-treated patients than in the placebo-treated patients at end point (Table 3). These changes are more closely associated with disease end points than with patient outcomes.

TABLE 3
MEAN PERCENTAGE (ACTUAL) CHANGES FROM BASELINE IN LABORATORY VALUES
AND VITAL SIGNS IN PATIENTS TREATED WITH SIBUTRAMINE 10 AND 15 MG
COMPARED WITH PLACEBO

                           End Point, All Patients

                             Placebo

Patients, N                         114
  Triglycerides (mmol/L)   -1.3 (-0.21)
  Cholesterol (mmol/L)       1.8 (0.08)
  Glucose (mmol/L)         -0.2 (-0.16)
  Uric acid (mmol/L)        -2.4 (-9.1)
Patients, N                         153
  Systolic blood
    pressure, mm Hg                -0.5
  Diastolic blood
    pressure, mm Hg                -0.9
  Pulse rate, bpm                   0.1

                              End Point, All Patients

                                   Sibutramine
                                      10 mg

Patients, N                                        112
  Triglycerides (mmol/L)                  -6.1 (-0.26)
  Cholesterol (mmol/L)                      2.1 (0.08)
  Glucose (mmol/L)                        -0.9 (-0.21)
  Uric acid (mmol/L)       -5.8(*)([sections]) (-21.0)
Patients, N                                        154
  Systolic blood
    pressure, mm Hg                                1.0
  Diastolic blood
    pressure, mm Hg                      1.6([dagger])
  Pulse rate, bpm                                  1.8

                                       End Point, All Patients

                                             Sibutramine
                                               15 mg

Patients, N                                                      123
  Triglycerides (mmol/L)                    -9.8([sections]) (-0.44)
  Cholesterol (mmol/L)                                    1.9 (0.09)
  Glucose (mmol/L)                                      -1.1 (-0.19)
  Uric acid (mmol/L)       -8.0([double dagger])([parallel]) (-26.5)
Patients, N                                                      149
  Systolic blood
    pressure, mm Hg                                              0.3
  Diastolic blood
    pressure, mm Hg                                             -0.1
  Pulse rate, bpm                                      3.5([dagger])

NOTE: All significance tests relate to analyses concerning
percentage changes.

(*) P <.05 versus all placebo.

([dagger]) P <0.1 versus all placebo.

([double dagger]) P <.001 versus all placebo.

([sections]) P <.05 versus baseline.

([parallel]) P <.01 versus baseline.