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The Role of Resveratrol Administration in Human Obesity.
Mongioì, LM, La Vignera, S, Cannarella, R, Cimino, L, Compagnone, M, Condorelli, RA, Calogero, AE
International journal of molecular sciences. 2021;(9)
Abstract
Obesity is a widespread disease that is associated with numerous and serious comorbidities. These include metabolic syndrome, diabetes mellitus, cardiovascular-cerebrovascular disease, hypertension, obstructive sleep apnea syndrome, cancer, and sexual and hormonal disorders. The treatment of obesity has therefore become a goal of great clinical and social relevance. Among the therapeutic strategies against obesity, resveratrol has aroused great interest. This polyphenol has anticancer and antioxidant properties and cytoprotective and anti-inflammatory effects. Other favorable effects attributed to resveratrol are anti-lipid, anti-aging, anti-bacterial, anti-viral, and neuroprotective actions. Administration of resveratrol appears to improve the metabolic profile in obese and/or insulin-resistant patients. This article aims to review the main results of clinical studies evaluating the effects of administering resveratrol alone in overweight/obese patients.
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Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes.
Scheen, AJ, Van Gaal, LF
The lancet. Diabetes & endocrinology. 2014;(11):911-22
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Abstract
The increasing prevalence of obesity is contributing substantially to the ongoing epidemic of type 2 diabetes. Abdominal adiposity, a feature of ectopic fat syndrome, is associated with silent inflammation, abnormal hormone secretion, and various metabolic disturbances that contribute to insulin resistance and insulin secretory defects, resulting in type 2 diabetes, and induce a toxic pattern that leads to cardiovascular disease, liver pathologies, and cancer. Despite the importance of weight control strategies in the prevention and management of type 2 diabetes, long-term results from lifestyle or drug interventions are generally disappointing. Furthermore, most of the classic glucose-lowering drugs have a side-effect of weight gain, which renders the management of most overweight or obese people with type 2 diabetes even more challenging. Many anti-obesity pharmacological drugs targeting central control of appetite were withdrawn from the market because of safety concerns. The gastrointestinal lipase inhibitor orlistat was the only anti-obesity drug available until the recent US, but not European, launch of phentermine-controlled-release topiramate and lorcaserin. Improved knowledge about bodyweight regulation opens new prospects for the potential use of peptides derived from the gut or the adipose tissue. Combination therapy will probably be necessary to avoid compensatory mechanisms and potentiate initial weight loss while avoiding weight regain. New glucose-lowering treatments, especially glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, offer advantages over traditional antidiabetic drugs by promoting weight loss while improving glucose control. In this Review, we explore the overlapping pathophysiology and also how various treatments can, alone or in combination, combat the dual burden of obesity and type 2 diabetes.
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Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide.
Astrup, A, Carraro, R, Finer, N, Harper, A, Kunesova, M, Lean, ME, Niskanen, L, Rasmussen, MF, Rissanen, A, Rössner, S, et al
International journal of obesity (2005). 2012;(6):843-54
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OBJECTIVE Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss (secondary outcome) over 2 years. DESIGN A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers. SUBJECTS A total of 564 adults (n=90-98 per group; body mass index 30-40 kg m(-2)) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500 kcal deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n=90-95), placebo (n=98) or open-label orlistat (120 mg × 3, n=95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007-April 2009 and is registered with Clinicaltrials.gov, number NCT00480909. RESULTS From randomization to year 1, liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7-8.0) more weight than those on placebo and 3.8 kg (1.6-6.0) more than those on orlistat (P0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n=184) lost 3.0 kg (1.3-4.7) more weight than those on orlistat (n=95; P<0.001). Completers on liraglutide 2.4/3.0 mg (n=92) maintained a 2-year weight loss of 7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids. CONCLUSION Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors.
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Effects of the new dual PPAR α/δ agonist GFT505 on lipid and glucose homeostasis in abdominally obese patients with combined dyslipidemia or impaired glucose metabolism.
Cariou, B, Zaïr, Y, Staels, B, Bruckert, E
Diabetes care. 2011;(9):2008-14
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OBJECTIVE We evaluated the metabolic effects and tolerability of GFT505, a novel dual peroxisome proliferator-activated receptor α/δ agonist, in abdominally obese patients with either combined dyslipidemia or prediabetes. RESEARCH DESIGN AND METHODS The S1 study was conducted in 94 patients with combined dyslipidemia while the S2 study was conducted in 47 patients with prediabetes. Participants were randomly assigned in a double-blind manner to GFT505 at 80 mg/day or placebo for 28 (S1) or 35 (S2) days. Primary efficacy end points were changes from baseline at week 4 in both fasting plasma triglycerides and HDL cholesterol in the S1 group and 2-h glucose upon oral glucose tolerance test in the S2 group. RESULTS In comparison with placebo, GFT505 significantly reduced fasting plasma triglycerides (S1: least squares means -16.7% [95% one-sided CI -∞ to -5.3], P = 0.005; S2: -24.8% [-∞ to -10.5], P = 0.0003) and increased HDL cholesterol (S1: 7.8% [3.0 to ∞], P = 0.004; S2: 9.3% [1.7 to ∞], P = 0.009) in both studies, whereas LDL cholesterol only decreased in S2 (-11.0% [ -∞ to -3.5], P = 0.002). In S2, GFT505 did not reduce 2-h glucose (-0.52 mmol/L [-∞ to 0.61], P = 0.18) but led to a significant decrease of homeostasis model assessment of insulin resistance (-31.4% [-∞ to 12.5], P = 0.001), fasting plasma glucose (-0.37 mmol/L [-∞ to -0.10], P = 0.01) and fructosamine (-3.6% [-∞ to -0.20], P = 0.02). GFT505 also reduced γ glutamyl transferase levels in both studies (S1: -19.9% [-∞ to -12.8], P < 0.0001; S2: -15.1% [-∞ to -1.1], P = 0.004). No specific adverse safety signals were reported during the studies. CONCLUSIONS GFT505 may be considered a new drug candidate for the treatment of lipid and glucose disorders associated with the metabolic syndrome.
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Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels.
Panidis, D, Farmakiotis, D, Rousso, D, Kourtis, A, Katsikis, I, Krassas, G
Fertility and sterility. 2008;(4):899-906
Abstract
OBJECTIVE To investigate the combined effect of diet and orlistat, for 24 weeks, on anthropometric features, hormonal parameters, and indices of insulin resistance in obese women with polycystic ovary syndrome (PCOS) and in obese women without the syndrome. DESIGN Prospective clinical study. SETTING Department of obstetrics and gynecology in a major university in Greece. PATIENT(S): Eighteen selected women with PCOS were matched for age and body mass index with 14 obese control women. INTERVENTION(S): Subjects were prescribed an energy-restricted diet, and orlistat (120 mg, 3 times per d) was administered to all subjects for 24 weeks. MAIN OUTCOME MEASURE(S): At baseline, week 12, and week 24, after an overnight fast, blood samples were collected, and serum levels of FSH, LH, PRL, T, Delta(4)A, DHEAS, 17 alpha-hydroxyprogesterone, sex hormone-binding globulin, glucose, and insulin were measured. RESULT(S): Testosterone levels were significantly decreased with treatment in women with PCOS; this decrease was attributed to the first trimester, whereas T levels did not change during the second 12-week period. In women with PCOS, insulin levels and HOMA-IR values were decreased during the first 12 weeks, whereas no significant change was observed during the second trimester. CONCLUSION(S): Orlistat administration, combined with diet, for 24 weeks, resulted in significant weight loss and improvement of insulin resistance in obese women, with or without PCOS. Moreover, T levels were significantly decreased in women with PCOS. There appears to be a trend during the first 12-week period for greater improvement of metabolic and hormonal parameters in women with PCOS.
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[Cardiometabolic effects of rimonabant in obese/overweight subjects with dyslipidaemia or type 2 diabetes].
Scheen, AJ, Van Gaal, LF
Revue medicale de Liege. 2007;(2):81-5
Abstract
Rimonabant (Acomplia) is the first selective CB1 receptor blocker of the endocannabinoid system. It has been evaluated in the RIO ("Rimonabant In Obesity and related disorders") programme including above 6.600 overweight/obese patients with or without comorbidities followed for 1 to 2 years. Compared to placebo, rimonabant 20 mg/day consistently increases weight loss, reduces waist circumference, increases HDL cholesterol, lowers triglyceride levels, diminishes insulin resistance, and reduces the prevalence of metabolic syndrome. In patients with type 2 diabetes, rimonabant also diminishes HbA1c levels, an effect confirmed in the recent SERENADE trial. Almost half of the metabolic effects occurs beyond weight loss, suggesting direct peripheral effects of rimonabant. Rimonabant is indicated in Europe as an adjunct to diet and exercise for the treatment of obese patients, or overweight patients with associated risk factor(s), such as type 2 diabetes or dyslipidaemia.
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Managing nonalcoholic fatty liver disease: recommendations for family physicians.
Grattagliano, I, Portincasa, P, Palmieri, VO, Palasciano, G
Canadian family physician Medecin de famille canadien. 2007;(5):857-63
Abstract
OBJECTIVE To review evidence on the diagnosis and management of nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease in human beings. SOURCES OF INFORMATION The literature was searched for clinical trials and review articles on NAFLD. Levels I and II evidence indicates the benefit of both lifestyle and pharmacologic interventions for NAFLD and nonalcoholic steatohepatitis (NASH). MAIN MESSAGE Scientific evidence does not currently support systematic screening for NAFLD. Both NAFLD and NASH are frequently discovered in overweight and obese patients with asymptomatic elevation of serum aminotransferase levels. Ultrasonography detects the presence of a fatty liver, but is unreliable for detecting and quantifying liver fibrosis. Patients with NAFLD should be monitored for possible progression to NASH, particularly if they have diabetes or metabolic syndrome. Although diet and exercise are the mainstays of treatment, medication might be warranted if an appropriate diet and regular physical activity do not improve biochemical markers and liver morphology. Referral for liver biopsy and further evaluation should be considered for those at higher risk of developing NASH. CONCLUSION Although most patients with NAFLD have a benign course, some progress to NASH, liver cirrhosis, and hepatocellular carcinoma. These patients should be carefully monitored for progression of disease and treated for associated metabolic disturbances. An integrated approach to care is essential.
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Vascular risks and management of obesity in children and adolescents.
Jolliffe, CJ, Janssen, I
Vascular health and risk management. 2006;(2):171-87
Abstract
Childhood obesity has reached epidemic proportions in many countries. Pediatric obesity is associated with the development of cardiovascular (CV) risk factors including type 2 diabetes, hypertension, dyslipidemia, and the metabolic syndrome. It is also associated with an increased risk of CV disease (CVD) in adulthood. Moreover, obesity and CVD risk factors in obese youth tend to track into adulthood, further increasing the risk of adult CVD. Consequently, the treatment and prevention of childhood overweight and obesity has become a public health priority. Proper nutrition and increased physical activity are the main focus of these efforts; however, few studies have shown positive results. Treatment options for obesity in youth also include pharmacotherapy and surgery. While pharmacotherapy appears promising, additional evidence is needed, especially with respect to the long-term impact, before it becomes a widespread treatment option in the pediatric population.
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[Rimonabant improves cardiometabolic risk profile in obese or overweight subjects: overview of RIO studies].
Scheen, AJ, Van Gaal, LG, Després, JP, Pi-Sunyer, X, Golay, A, Hanotin, C
Revue medicale suisse. 2006;(76):1916-23
Abstract
RIO (Rimonabant In Obesity and related disorders) is a large phase 3 programme (>6600 patients) evaluating the efficacy and safety of rimonabant (5 or 20 mg/day), a CBI receptor antagonist of endocannabinoid system, in obese or overweight patients with or without comorbidities (RIO-Europe and RIO-North America), with untreated dyslipidaemia (RIO-Lipids) or with type 2 diabetes treated with metformin or sulfonylurea (RIO-Diabetes). Compared to placebo, rimonabant 20 mg/day consistently increases weight loss, reduces waist circumference, increases HDL cholesterol, lowers triglyceride levels, diminishes insulin resistance, and reduces the prevalence of metabolic syndrome. Almost half of the metabolic effects, including adiponectin increase, occur beyond weight loss, suggesting a direct peripheral effect of rimonabant.