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

Our analysis takes the patients who withdrew from the study into account.[32] Pooled rates of withdrawal for any reason were similar in the 3 treatment groups: placebo, 83 patients (51%); sibutramine 10 mg, 79 (49%); and sibutramine 15 mg, 67 (42%). The completion rate for the 1-year study was 53%, which is generally consistent with weight loss programs.[37] Regarding the primary outcome analysis, fewer patients in the sibutramine groups than in the placebo group withdrew for lack of efficacy or adverse events. Using the log-rank test, there was no statistically significant difference between treatment groups in time to withdrawal, overall withdrawal rate, or withdrawal rate due to adverse events or lack of efficacy. Both sibutramine-treated groups had more patients in each category of weight loss above 5% (P=.001; Table 2). Pairwise comparisons showed a statistically significant difference versus placebo in favor of sibutramine 10 mg (P=.04)and sibutramine 15 mg (P [is less than] .001).

TABLE 2
MEAN CHANGE (ACTUAL AND PERCENTAGE) IN BODY WEIGHT AND NUMBER
OF PATIENTS IN EACH STUDY OUTCOME CATEGORY AFTER 12 MONTHS OF
TREATMENT (LOCF)

                                        Treatment Group

                                        Placebo (N=157)

Mean change in body weight,
kg (95% CI)                           -1.6 (-2.3 to -0.9)

Mean % change in body weight
(95% CI)                              -1.8 (-2.5 to -1.0)
  [is greater than or equal to] 5%
    baseline weight loss, no. (%)                  32(20)
  [is greater than or equal to] 10%
    baseline weight loss, no. (%)                   11(7)

OUTCOME CATEGORY([double dagger])                 (N=163)

Treatment weight losses
  >20% weight loss, no. (%)                          1(1)
  15.1%-20.0% weight loss, no. (%)                   1(1)
  10.1-15.0% weight loss, no. (%)                    4(2)
  5.1%-10.0% weight loss, no. (%)                  16(10)
  0.1%-5.0% weight loss, no. (%)                   29(18)

No change in weight, no. (%)                         1(1)

Weight gain, no. (%)                               28(17)

Withdrew for other reasons (shown
in Figure 1), no. (%)                              48(29)

Withdrew for lack of efficacy or
adverse event, no. (%)                             34(21)

                                             Treatment Group

                                        10-mg Sibutramine (N=154)

Mean change in body weight,
kg (95% CI)                                  -4.4(*) (-5.4 to -3.4)

Mean % change in body weight
(95% CI)                              -5.0([dagger]) (-6.1 to -3.9)
  [is greater than or equal to] 5%
    baseline weight loss, no. (%)                 60 (39)([dagger])
  [is greater than or equal to] 10%
    baseline weight loss, no. (%)                        30 (19)(*)

OUTCOME CATEGORY ([double dagger])                          (N=161)

Treatment weight losses
  >20% weight loss, no. (%)                                    3(2)
  15.1%-20.0% weight loss, no. (%)                            11(7)
  10.1-15.0% weight loss, no. (%)                             11(7)
  5.1%-10.0% weight loss, no. (%)                             21(3)
  0.1%-5.0% weight loss, no. (%)                              21(3)

No change in weight, no. (%)                                   0(0)

Weight gain, no. (%)                                          15(9)

Withdrew for other reasons (shown
in Figure 1), no. (%)                                        56(35)

Withdrew for lack of efficacy or
adverse event, no. (%)                                       23(14)

                                             Treatment Group

                                        15-mg Sibutramine (N=153)

Mean change in body weight,
kg (95% CI)                           -6.4([dagger]) (-7.4 to -5.3)

Mean % change in body weight
(95% CI)                               -7.3([dagger]) (-8.5 to 6.2)
  [is greater than or equal to] 5%
    baseline weight loss, no. (%)                 87 (57)([dagger])
  [is greater than or equal to] 10%
    baseline weight loss, no. (%)                 52 (34)([dagger])

OUTCOME CATEGORY ([double dagger])                          (N=161)

Treatment weight losses
  >20% weight loss, no. (%)                                    6(4)
  15.1%-20.0% weight loss, no. (%)                          8(5)(*)
  10.1-15.0% weight loss, no. (%)                         23(14)(*)
  5.1%-10.0% weight loss, no. (%)                            24(15)
  0.1%-5.0% weight loss, no. (%)                             18(11)

No change in weight, no. (%)                                   2(1)

Weight gain, no. (%)                                          13(8)

Withdrew for other reasons (shown
in Figure 1), no. (%)                                        44(27)

Withdrew for lack of efficacy or
adverse event, no. (%)                                       22(14)

LOCF denotes last observation carried forward; CI, confidence interval.

(*) P <.01 versus placebo.

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

([double dagger]) Overall level of significance for comparison of
treatment groups: 10-mg sibutramine versus placebo,
P=.04; 15-mg sibutramine versus placebo, P <.001; 10-mg
versus 15-mg sibutramine, P >.05.

A significantly greater proportion of patients in the 2 sibutramine groups lost at least 5% and 10% of their baseline body weight (Table 2). Mean weight reduction was significantly greater in the sibutramine groups than in the placebo group. Mean reductions in BMI reflected those in body weight and were significantly greater with 10 mg sibutramine (1.7 kg/[m.sup.2]) and 15 mg sibutramine (2.4 kg/[m.sup.2] than with placebo (0.6 kg/[m.sup.2]; P [is less than] .001). The reduction in BMI was significantly greater with 15 mg sibutramine than 10-mg sibutramine (P [is less than] .05).

Patients treated with 10 mg or 15 mg sibutramine once daily lost more weight at each monthly assessment than those treated with placebo (Figure 2). Weight loss was dose related, and maximal weight loss occurred by month 6 in all treatment groups. During the 4 weeks after treatment cessation (at whatever time this occurred), there were small weight increases in all treatment groups. Ten (6%) patients in the placebo group withdrew because of lack of efficacy compared with 5 (3%) in the sibutramine 10 mg group and 2 (1%) in the sibutramine 15-mg group.