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A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion

By February 10, 2006September 24th, 2020No Comments


International Journal of Obesity

R H Lustig 1 ,
F Greenway,
P Velasquez-Mieyer,
D Heimburger,
D Schumacher,
D Smith,
W Smith,
N Soler,
G Warsi,
W Berg,
J Maloney,
J Benedetto,
W Zhu,
J Hohneker

Objective: To compare changes in weight in obese patients who received long-acting
octreotide (octreotide LAR) at one of three dose levels (20, 40, or 60 mg)
or placebo over 6 months and to identify the lowest dose of octreotide LAR
that safely achieved optimal weight loss.
Design: Randomized, double-blind, placebo-controlled trial of octreotide LAR at
three dose levels.
Patients: A total of 172 adults (28 men and 144 women) with at least moderate
obesity (body mass index (BMI) range 30-65 kg/m2) and evidence of insulin
hypersecretion were enrolled. Patients were predominantly either Caucasian
(50.0%) or African American (45.3%). The mean age (38 +/- 11 year), weight
(110.7 +/- 23 kg), and BMI (39.8 +/- 6.5 kg/m2) were similar across the
four treatment groups.
Measurements: Efficacy measures included weight, BMI, fasting serum glucose;
triglycerides; percentage of total body fat and abdominal fat as measured
by dual-energy X-ray absorptiometry; skin fold thickness; waist-to-hip
circumference; leptin; percentage of carbohydrates, fat, and protein
ingested; nutritional evaluation (including dietary analysis–3-day food
record); quality of life (QoL; using the Impact of Weight on Quality of
Life-Lite); Beck Depression Inventory; and Carbohydrate Craving
Questionnaire. Safety measures included medical history, vital signs,
physical examinations, hematology, blood chemistries, thyroid function
tests, hemoglobin A1c, gallbladder ultrasound, electrocardiograms, and
adverse events.
Results: After 6 months of treatment, patients receiving 40 or 60 mg of octreotide
LAR experienced statistically significant weight loss compared to baseline,
with mean differences from placebo in percent weight change of -1.98 and
-1.87%, respectively. This finding was accompanied by statistically
significant mean decreases in BMI compared to baseline, that is, a mean
decrease of 0.73 and 0.79 kg/m2 for the 40 and 60 mg treatment arms,
respectively. The observed weight loss was progressive during the 6-month
treatment in the two higher dose groups. The lowest dose to reach
statistical significance in weight loss after 6 months’ treatment was 40
mg. Post hoc analysis revealed a 3.5-3.8% weight loss at month 6 in the two
higher dose groups among Caucasian patients having insulin secretion
greater than the median of the cohort, defined as CIR(gp) (corrected
insulin response at the glucose peak) > or = 1.43. There were no
statistically significant changes in QoL scores, body fat, leptin
concentration, Beck Depression Inventory, or macronutrient intake. Mean
changes of blood glucose AUC(0-180 min) during an oral glucose tolerance
test in patients taking octreotide LAR were 39-40 mg/dl h higher than those
on placebo. A total of 7-21% of the patients taking octreotide LAR reached
a 5% or greater decrease in body weight from Baseline, compared to 11% for
the placebo group. This was not statistically significant. The most common
adverse events included diarrhea, headache, cholelithiasis, nausea, and
abdominal pain.
Conclusion: Octreotide LAR given at 40 or 60 mg resulted in statistically significant
weight loss. A post hoc analysis stratifying patients by race and CIR(gp)
indicated that Caucasian patients with the greater degree of insulin
hypersecretion appeared to derive the most benefit from treatment. The
observed safety profile was consistent with the known effects of octreotide
from previous studies.


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