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
Robert H. Lustig,Frank L. Greenway,Pedro Velasquez-Mieyer,D Heimburger,D Schumacher,Diane K. Smith,W Smith,N Soler,Ghulam Warsi,William Berg,J Maloney,John Benedetto,W. Zhu,John Hohneker +13 more
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TLDR
It is indicated that Caucasian patients with the greater degree of insulin hypersecretion appeared to derive the most benefit from treatment, and the observed safety profile was consistent with the known effects of octreotide from previous studies.Abstract:
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. Randomized, double-blind, placebo-controlled trial of octreotide LAR at three dose levels. 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. 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. 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 CIRgp (corrected insulin response at the glucose peak) ⩾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 AUC0–180 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. Octreotide LAR given at 40 or 60 mg resulted in statistically significant weight loss. A post hoc analysis stratifying patients by race and CIRgp 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.read more
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Pediatric Obesity-Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline.
Dennis M. Styne,Silva A. Arslanian,Ellen L. Connor,I. S. Farooqi,M. Hassan Murad,Janet H. Silverstein,Jack A. Yanovski +6 more
TL;DR: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence on pediatric obesity.
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Gilbert P. August,Sonia Caprio,Ilene Fennoy,Michael Freemark,Francine R. Kaufman,Robert H. Lustig,Janet H. Silverstein,Phyllis W. Speiser,Dennis M. Styne,Victor M. Montori +9 more
TL;DR: Practice guidelines for the treatment and prevention of pediatric obesity are formulated and bariatric surgery for adolescents with BMI above 50 kg/m2, or BMI above 40 kg/ m2 with severe comorbidities in whom lifestyle modifications and/or pharmacotherapy have failed are suggested.
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Hyperinsulinemia Drives Diet-Induced Obesity Independently of Brain Insulin Production
Arya E. Mehran,Nicole M. Templeman,G. Stefano Brigidi,Gareth E. Lim,Kwan-Yi Chu,Xiaoke Hu,José Diego Botezelli,Ali Asadi,Bradford G. Hoffman,Timothy J. Kieffer,Shernaz X. Bamji,Susanne M. Clee,James D. Johnson +12 more
TL;DR: Genetic evidence that pathological circulating hyperinsulinemia drives diet-induced obesity and its complications is provided and white adipose tissue is reprogrammed to express uncoupling protein 1 and increase energy expenditure.
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How Western Diet And Lifestyle Drive The Pandemic Of Obesity And Civilization Diseases.
TL;DR: It is suggested that the diet-related key changes in the developmental process include an increased production of reactive oxygen species and oxidative stress, development of hyperinsulinemia and insulin resistance, low-grade inflammation and an abnormal activation of the sympathetic nervous system and the renin-angiotensin system, all of which play pivotal roles in the development of diseases of civilization.
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Effects of somatostatin analogs on glucose homeostasis: a metaanalysis of acromegaly studies.
Gherardo Mazziotti,Irene Floriani,Irene Floriani,Irene Floriani,Stefania Bonadonna,Stefania Bonadonna,Stefania Bonadonna,Valter Torri,Valter Torri,Valter Torri,Philippe Chanson,Andrea Giustina,Andrea Giustina,Andrea Giustina +13 more
TL;DR: The data suggest that modifications of glucose homeostasis induced by SSA may have an overall minor clinical impact in acromegaly, although with high inconsistency among trials.
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