Pharmacotherapy For Obesity Research Articles

Obesity Pharmacotherapy in Patients With Type 2 Diabetes.

IN BRIEF Patients with obesity and type 2 diabetes are key targets for weight loss. Given the lack of behavioral weight loss in most patients, obesity pharmacotherapy options should be considered in this patient population. This article reviews key pharmacotherapy options for patients with coexisting obesity and type 2 diabetes. Diabetes medications that are associated with weight gain should be avoided in these patients if possible.

Past, present and future of pharmacotherapy for obesity

Conventional treatment for obesity with diet, exercise and bariatric surgery has limitations; thus, it is necessary to have pharmacological tools. In the past, different drugs were marketed that were withdrawn due to safety problems. There are currently 3 drugs approved by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) for obesity therapy (orlistat, combination of bupropion and delayed-release naltrexone and liraglutide) and two more only authorized by FDA (lorcaserin and the combination of phentermine and extended release topiramate). It is recommended to use as a second therapeutic line and its choice should be individualized taking into account multiple aspects such as expected weight loss, route of administration, safety profile and cost. Currently there are several drugs under development that act on different therapeutic targets.

Proportional Feedback Control of Energy Intake During Obesity Pharmacotherapy

ObjectiveObesity pharmacotherapies result in an exponential time course for energy intake whereby large early decreases dissipate over time. This pattern of declining drug efficacy to decrease energy intake results in a weight loss plateau within approximately one year. We aimed to elucidate the physiology underlying the exponential decay of drug effects on energy intake.MethodsWe examined the placebo-subtracted energy intake time courses during long-term obesity pharmacotherapy trials for 14 different drugs or drug combinations within the theoretical framework of a proportional feedback control system regulating human body weight.ResultsAssuming each obesity drug had a relatively constant effect on average energy intake and did not affect other model parameters, our model correctly predicted that long-term placebo-subtracted energy intake was linearly related to early reductions in energy intake according to a pre-specified equation with no free parameters. The simple model explained about 70% of the variance between drug studies with respect to the long-term effects on energy intake, although a significant proportional bias was evident.ConclusionsThe exponential decay over time of obesity pharmacotherapies to suppress energy intake can be interpreted as a relatively constant effect of each drug superimposed on a physiological feedback control system regulating body weight.

Current pharmacotherapy for obesity.

More than one-third of adults in the USA have obesity, which causes, exacerbates or adversely impacts numerous medical comorbidities, including diabetes mellitus and cardiovascular disease. Despite intensive lifestyle modifications, the disease severity warrants further aggressive intervention, including pharmacotherapy, medical devices and bariatric surgery. Noninvasive anti-obesity drugs have thus now resurfaced as targeted adjunctive therapeutic approaches to intensive lifestyle intervention, bridging the gap between lifestyle and bariatric surgery. In this Review, we discuss FDA-approved anti-obesity drugs in terms of safety and efficacy. As most of these drugs have a mean percentage weight loss reported in clinical trials but individual variations in response rates, a future direction of obesity pharmacotherapy research might include the potential for personalized medicine to target early responders to these anti-obesity drugs.

Current pharmacotherapies for obesity: A practical perspective.

To review the currently available pharmacotherapies for obesity management with a particular focus on the United States. Narrative review based on literature searches and the latest prescribing information (up to July 2017). Obesity pharmacotherapies may assist those individuals who have obesity, or overweight with comorbidities, who have failed to maintain weight loss with lifestyle modifications alone (caloric restriction and increased physical activity). Currently approved options in the United States include phentermine for short-term use and five obesity pharmacotherapies that can be used long-term (orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion, and liraglutide 3.0 mg). If the use of an obesity pharmacotherapy is indicated, treatment should be selected to provide the most appropriate option for each individual and their circumstances. Variables such as contraindications, individual comorbidities, patient choice, patient readiness to incorporate additional behavioral changes (e.g., alcohol prohibition), and cost should guide choices. Each of the obesity pharmacotherapies has advantages and disadvantages that can help guide treatment choice. Those receiving treatment may also have individual preferences based on factors such as administration route, frequency of dosing, and/or safety profile. In addition, some options may be particularly appropriate for patients with common obesity-related complications such as depression or diabetes.

The place of central-acting drugs in the algorithms of treatment of primary obesity

Pharmacotherapy is an essential component of obesity treatment, as well as efforts focused on changing the lifestyle, correcting the food consumption and increasing the physical activity. The administration of central-acting drugs as pharmacotherapy of obesity is pathogenetically justified and allows improving the effectiveness of treatment. In this article, the use of sibutramine, a serotonin and norepinephrine reuptake inhibitor, is considered in various aspects of endocrinologists practice. In addition to aforesaid there is an application of a specific clinical observation.

Current Drug Targets in Obesity Pharmacotherapy - A Review.

Obesity, an impending global pandemic, is not being effectively controlled by current measures such as lifestyle modifications, bariatric surgery or available medications. Its toll on health and economy compels us to look for more effective measures. Fortunately, the advances in biology and molecular technology have been in our favour for delineating new pathways in the pathophysiology of obesity and have led to subsequent development of new drug targets. Development of antiobesity drugs has often been riddled with problems in the past. Some of the recently approved drugs for pharmacotherapy of obesity have been lorcaserin, phentermine/topiramate and naltrexone/ bupropion combinations. Several promising new targets are currently being evaluated, such as amylin analogues (pramlintide, davalintide), leptin analogues (metreleptin), GLP-1 analogues (exenatide, liraglutide, TTP-054), MC4R agonists (RM-493), oxyntomodulin analogues, neuropeptide Y antagonists (velneperit), cannabinoid type-1 receptor blockers (AM-6545), MetAP2 inhibitors (beloranib), lipase inhibitors (cetilistat) and anti-obesity vaccines (ghrelin, somatostatin, Ad36). Many of these groups of drugs act as "satiety signals" while others act by antagonizing orexigenic signals, increasing fat utilisation and decreasing absorption of fats. Since these targets act through various pathways, the possibility of combined use of two or more classes of these drugs unlocks numerous therapeutic avenues. Hence, the dream of personalized management of obesity might be growing closer to reality.

Tailoring pharmacotherapy to specific eating behaviours in obesity: Can recommendations for personalised therapy be made from the current data?

Pharmacotherapy provides an adjunct to behaviour modification in the management of obesity. There are a number of new drug therapies purportedly targeting appetite; liraglutide, and bupropion/naltrexone, which are European Medicines Agency and US Food and Drug Administration (FDA) approved, and lorcaserin and phentermine/topiramate, which have FDA approval only. Each of the six drugs, used singly or in combination, has distinct pharmacological, and presumably distinct behavioural, mechanisms of action, thus the potential to provide defined therapeutic options to personalise the management of obesity. Yet, with regard to pharmacotherapy for obesity, we are far from true personalised medicine. We review the limited mechanistic data with four mono and combination pharmacotherapies, to assess the potential for tailoring their use to target specific obesogenic behaviours. Potential treatment options are considered, but in the absence of adequate research in respect to effects of these drugs on eating behaviour, neural activity and psychological substrates that underlie poorly controlled eating, we are far from definitive therapeutic recommendations. Specific mechanistic studies and broader behavioural phenotyping, possibly in conjunction with pharmacogenetic research, are required to characterise responders for distinct pharmacotherapeutic options.

Pharmacotherapy of Obesity: Clinical Trials to Clinical Practice.

This review provides an overview of the current state of drug therapy for obesity, with a focus on four new drug therapies-lorcaserin, phentermine/topiramate, naltrexone/bupropion, and liraglutide 3.0mg-which have been approved by the US Food and Drug Administration (FDA) for long-term management of obesity since 2012. Topics discussed in this paper include rationale for pharmacotherapy, history of antiobesity drugs, and efficacy and safety data from randomized controlled trials with implications for clinical practice. Weight loss achieved by currently approved drugs ranges from approximately 3 to 9%, above and beyond weight loss with lifestyle counseling alone, after a year. Response and attrition rates in clinical trials indicate that the benefits of pharmacotherapy range from substantial for some patients, modest for others, and no benefits for others still. Decisions regarding selection of a suitable drug from the available pharmacotherapy options and duration of treatment should be based on the expected and observed benefit-to-risk balance and tailored to the needs of each individual patient using the principles of shared decision-making.

Aggressive clinical approach to obesity improves metabolic and clinical outcomes and can prevent bariatric surgery: a single center experience.

BackgroundThe number of bariatric procedures has exponentially increased in the past decade, as a result of the lack of successful clinical weight-loss interventions. The main reasons for the failure of clinical obesity management are: (1) anti-obesity medications are administered as monotherapies (or pre-combined drugs); (2) lack of combination between pharmacotherapy and non-pharmacological modalities; (3) short duration of pharmacotherapy for obesity; (4) lack of weight-loss maintenance strategies; (5) misunderstanding of the complex pathophysiology of obesity; and (6) underprescription of anti-obesity medications. We developed a protocol that can potentially overcome the drawbacks that may lead to the failure of clinical therapy for obesity. The aim of this study is therefore to report the clinical and metabolic effects of our proposed obesity-management protocol over a 2-year period, and to determine whether this more intensive approach to obesity management is feasible and a possible alternative to bariatric surgery in patients with moderate-to-severe obesity.MethodsThis retrospective study involved 43 patients in whom bariatric surgery was indicated. Patients underwent an intensive anti-obesity protocol that included pharmacotherapy with multiple drugs; intense surveillance with monthly body analysis by air-displacement plethysmography, electrical bioimpedance, and 3D body scans; weekly psychotherapy; diet planning with a dietician every 2 months; and exercises at least 3 times a week with exercises prescribed by a personal trainer at least once a month. Body weight (BW), total weight excess (TWE), obesity class, body mass index, fat weight, muscle weight, waist circumference, and visceral fat were analyzed. Markers of lipid and glucose metabolism, liver function, and inflammation were also evaluated. Therapeutic success was defined as >20% BW loss or >50% decrease in TWE after 1 year.ResultsSignificant improvements were observed in all clinical and metabolic parameters. Thirty-eight (88.4%) patients achieved 10% BW loss, and 32 (74.4%) achieved 20% BW loss. TWE decreased by >50% in 35 (81.4%) patients. Forty (93.0%) patients were able to avoid bariatric surgery.ConclusionAn intensive clinical approach to obesity management can be an effective alternative to bariatric surgery, although further randomized controlled studies are necessary to validate our findings.

Practical Use of Pharmacotherapy for Obesity

Obesity management requires a multidisciplinary approach, as there are many factors that contribute to the development of obesity, as well as the preservation of excess weight once it has been gained. Diet, exercise, and behavior modification are key components of treatment. In addition to lifestyle changes, weight gain secondary to medications is an important modifiable risk factor. Even after appropriate lifestyle modification, and medication adjustments (where possible) to avoid agents that can contribute to weight gain, many patients are still unable to achieve clinically meaningful weight loss. Pharmacotherapy for obesity management can fill an important role for these patients. This article will review medications that can lead to weight gain and potential alternatives, currently approved anti-obesity medications and best practices to individualize the selection process, and the use of testosterone in men with hypogonadism and obesity.

Obesity pharmacotherapy: options and uses in clinical practice

Obesity pharmacotherapy: options and uses in clinical practice

Pharmacotherapy for obesity: What you need to know.

Weight-loss drugs are being evaluated for their role in obesity management. This article reviews the available weight-loss drugs, their efficacy and side effects, and their best clinical use.

Pharmacotherapy of Obesity: Past, Present and Future

In the review the evolution of pharmacotherapy of obesity is described, beginning with gerbal preparations, thyroid hormones and sympathomimetics and ending serotonergic agents, lipase inhibitors, peptide analogs and combined drugs. Approved drugs for the treatment of obesity, such as orlistat, lorcaserine, liraglutide, and combinations of phentermine/topiramat and naltrexone/bupropion are presented. Concluded that the most perspective drugs for the treatment of obesity in the future will be combinations of preparations with different mechanisms of action.

Effects of Liraglutide 3.0 Mg on Weight and Risk Factors in Hispanic Versus Non-Hipanic Populations: Subgroup Analysis from Scale Randomized Trials

Scarce data exist on pharmacotherapy for obesity in Hispanic individuals. This post hoc analysis of pooled data from 4 phase 3a trials compared the efficacy and safety of liraglutide 3.0 mg versus placebo, as adjunct to a reduced-calorie diet and physical activity, in Hispanic versus non-Hispanic subgroups. We conducted the double-blind randomized, placebo-controlled trials in adults with a minimum body mass index (BMI) of 27 kg/m2 with at least 1 comorbidity, or a minimum BMI of 30 kg/m2, at clinical research sites worldwide. In this analysis, we investigated possible differences in treatment effects between 534 Hispanics (10.4% of the population) and 4,597 non-Hispanics (89.6%) through statistical tests of interaction between subgroups and treatment. Variables examined included mean and categorical weight change, cardiovascular risk markers, and safety data. Both subgroups achieved clinically significant mean weight loss at end-of-treatment with liraglutide 3.0 mg versus placebo: Hispanics 7.0% versus 1.5%, treatment difference -5.1% (95% CI, -6.2 to -4.0); non-Hispanics 7.5% versus 2.3%, -5.2% (95% CI, -5.5 to -4.8). More individuals in both subgroups lost ≥5%, >10%, and >15% of their baseline weight with liraglutide 3.0 mg than with placebo. Efficacy endpoints generally did not vary with ethnicity (P>.05). Adverse events were comparable between ethnic subgroups, with more gastrointestinal disorders reported with liraglutide 3.0 mg than placebo. Efficacy and safety were largely similar between Hispanic and non-Hispanic subgroups. Results support that liraglutide 3.0 mg, used with a reduced-calorie diet and physical activity, can facilitate weight loss in Hispanic individuals. A1c = glycated hemoglobin BMI = body mass index CI = confidence interval FPG = fasting plasma glucose GLP-1 = glucagon-like peptide-1 hsCRP = high-sensitivity C-reactive protein SCALE = Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes T2DM = type 2 diabetes mellitus.

Endogenous Glucagon-like Peptide-1 Receptor Signaling in the Nucleus Tractus Solitarius is Required for Food Intake Control.

Alhough the glucagon-like peptide-1 (GLP-1) system is critical to energy balance control and is a target for obesity pharmacotherapies, the receptor-population-mediating effects of endogenous GLP-1 signaling are not fully understood. To address this, we developed a novel adeno-associated virus (AAV-GLP-1R) that utilizes short hairpin RNA to chronically knock down GLP-1 receptors (GLP-1R) in rats. As pharmacological studies highlight the hindbrain nucleus tractus solitarius (NTS) as a brain region important for GLP-1R-mediated effects on energy balance, AAV-GLP-1R was injected into the NTS to examine the role of endogenous NTS GLP-1R signaling in energy balance control. Chow intake and meal size were significantly increased following chronic NTS GLP-1R knockdown. In addition, NTS GLP-1R knockdown significantly increased self-administration of palatable food under both fixed and progressive ratio schedules of reinforcement. Collectively, these data demonstrate that endogenous NTS GLP-1R signaling is required for the control of food intake and motivation to feed, and provide a new strategy to investigate the importance of distinct GLP-1R populations in the control of a variety of functions.

Can we win the war on obesity with pharmacotherapy?

ABSTRACTIntroduction: Obesity is a major health concern for several countries. The United States (U.S.) has arguably led the world in the percentage of overweight and/or obese per capita for several decades. As a result, numerous FDA-approved pharmacotherapeutic options are available for the long-term treatment of obesity. Although most of these medications have been on the U.S. market for a few years and have demonstrated efficacy for long-term weight loss in clinical trials, the impact of these medications on obesity in the U.S. has yet to be realized.Areas covered: We will review and evaluate why pharmacotherapy for obesity has not produced a meaningful reduction in the number of overweight and obese adults in the U.S.Expert commentary: Several obstacles, such as adverse drug effects, poor insurance coverage, not treating obesity as a chronic disease, and availability of other weight loss alternatives, has resulted in poor performance of pharmacotherapy for obesity in the U.S. market.

Obesogenic and Diabetogenic Effects of High-Calorie Nutrition Require Adipocyte BK Channels.

Elevated adipose tissue expression of the Ca2+- and voltage-activated K+ (BK) channel was identified in morbidly obese men carrying a BK gene variant, supporting the hypothesis that K+ channels affect the metabolic responses of fat cells to nutrients. To establish the role of endogenous BKs in fat cell maturation, storage of excess dietary fat, and body weight (BW) gain, we studied a gene-targeted mouse model with global ablation of the BK channel (BKL1/L1) and adipocyte-specific BK-deficient (adipoqBKL1/L2) mice. Global BK deficiency afforded protection from BW gain and excessive fat accumulation induced by a high-fat diet (HFD). Expansion of white adipose tissue-derived epididymal BKL1/L1 preadipocytes and their differentiation to lipid-filled mature adipocytes in vitro, however, were improved. Moreover, BW gain and total fat masses of usually superobese ob/ob mice were significantly attenuated in the absence of BK, together supporting a central or peripheral role for BKs in the regulatory system that controls adipose tissue and weight. Accordingly, HFD-fed adipoqBKL1/L2 mutant mice presented with a reduced total BW and overall body fat mass, smaller adipocytes, and reduced leptin levels. Protection from pathological weight gain in the absence of adipocyte BKs was beneficial for glucose handling and related to an increase in body core temperature as a result of higher levels of uncoupling protein 1 and a low abundance of the proinflammatory interleukin-6, a common risk factor for diabetes and metabolic abnormalities. This suggests that adipocyte BK activity is at least partially responsible for excessive BW gain under high-calorie conditions, suggesting that BK channels are promising drug targets for pharmacotherapy of metabolic disorders and obesity.

Exploring crucial aspects of diabetes and obesity

Exploring crucial aspects of diabetes and obesity

Current practices of obesity pharmacotherapy, bariatric surgery referral and coding for counselling by healthcare professionals.

SummaryIntroductionRates of obesity pharmacotherapy use, bariatric surgery and intensive behavioural counselling have been extremely low.ObjectivesThe primary objective of this study was to survey healthcare provider beliefs, practice and knowledge regarding obesity management.MethodsPrimary care physicians (PCPs), OB‐GYN physicians and nurse practitioners (NPs) responded to a web‐based survey related to drug therapy practice, bariatric surgery referral and reimbursement coding practice.ResultsRates of reported use of obesity pharmacotherapy appear to be increasing among PCPs, which is likely related to the approval of four new obesity pharmacotherapy agents since 2012. Rates of pharmacotherapy use among OB‐GYNs and NPs appear much lower. Similarly, few PCPs are averse to recommending bariatric surgery, but aversion among OB‐GYNs and NPs is significantly higher.ConclusionTogether, these observations suggest that OB‐GYN and NP populations are important targets for education about obesity management. Very few PCPs, OB‐GYNs or NPs use behavioural counselling coding for obesity. Better understanding of why this benefit is not being fully used could inform outreach to improve counselling rates.