Nick Finer

Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study

BACKGROUND Rimonabant, a selective cannabinoid type 1 receptor blocker, reduces bodyweight and improves cardiovascular and metabolic risk factors in non-diabetic overweight or obese patients. The aim of the RIO-Diabetes trial was to assess the efficacy and safety of rimonabant in overweight or obese patients with type 2 diabetes that was inadequately controlled by metformin or sulphonylureas. METHODS 1047 overweight or obese type 2 diabetes patients (body-mass index 27-40 kg/m2) with a haemoglobin A1c (HbA1c) concentration of 6.5-10.0% (mean 7.3% [SD 0.9] at baseline) already on metformin or sulphonylurea monotherapy were given a mild hypocaloric diet and advice for increased physical activity, and randomly assigned placebo (n=348), 5 mg/day rimonabant (360) or 20 mg/day rimonabant (339) for 1 year. Two individuals in the 5 mg/day group did not receive double-blind treatment and were thus not included in the final analysis. The primary endpoint was weight change from baseline after 1 year of treatment. Analyses were done on an intention-to-treat basis. This trial is registered at ClinicalTrials.gov, number NCT00029848. FINDINGS 692 patients completed the 1 year follow-up; numbers in each group after 1 year were much the same. Weight loss was significantly greater after 1 year in both rimonabant groups than in the placebo group (placebo: -1.4 kg [SD 3.6]; 5 mg/day: -2.3 kg [4.2], p=0.01 vs placebo; 20 mg/day: -5.3 kg [5.2], p<0.0001 vs placebo). Rimonabant was generally well tolerated. The incidence of adverse events that led to discontinuation was slightly greater in the 20 mg/day rimonabant group, mainly due to depressed mood disorders, nausea, and dizziness. INTERPRETATION These data indicate that 20 mg/day rimonabant, in combination with diet and exercise, can produce a clinically meaningful reduction in bodyweight and improve HbA1c and a number of cardiovascular and metabolic risk factors in overweight or obese patients with type 2 diabetes inadequately controlled by metformin or sulphonylureas.

Effect of Sibutramine on Cardiovascular Outcomes in Overweight and Obese Subjects

BACKGROUND The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. METHODS We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). RESULTS The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased. CONCLUSIONS Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.)

Management of Obesity in Adults: European Clinical Practice Guidelines

The development of consensus guidelines for obesity is complex. It involves recommending both treatment interventions and interventions related to screening and prevention. With so many publications and claims, and with the awareness that success for the individual is short-lived, many find it difficult to know what action is appropriate in the management of obesity. Furthermore, the significant variation in existing service provision both within countries as well as across the regions of Europe makes a standardised approach, even if evidence-based, difficult to implement. In formulating these guidelines, we have attempted to use an evidence-based approach while allowing flexibility for the practicing clinician in domains where evidence is currently lacking and ensuring that in treatment there is recognition of clinical judgment and of regional diversity as well as the necessity of an agreed approach by the individual and family. We conclude that i) physicians have a responsibility to recognise obesity as a disease and help obese patients with appropriate prevention and treatment, ii) treatment should be based on good clinical care and evidence-based interventions and iii) obesity treatment should focus on realistic goals and lifelong management.

Prevalence, Pathophysiology, Health Consequences and Treatment Options of Obesity in the Elderly: A Guideline

The prevalence of obesity is rising progressively, even among older age groups. By the year 2030–2035 over 20% of the adult US population and over 25% of the Europeans will be aged 65 years and older. The predicted prevalence of obesity in Americans, 60 years and older was 37% in 2010. The predicted prevalence of obesity in Europe in 2015 varies between 20 and 30% dependent on the model used. This means 20.9 million obese 60+ people in the USA in 2010 and 32 million obese elders in 2015 in the EU. Although cut-off values of BMI, waist circumference and percentages of fat mass have not been defined for the elderly (nor for the elderly of different ethnicity), it is clear from several meta-analyses that mortality and morbidity associated with overweight and obesity only increases at a BMI above 30 kg/m2. Thus, treatment should only be offered to patients who are obese rather than overweight and who also have functional impairments, metabolic complications or obesity-related diseases, that can benefit from weight loss. The weight loss therapy should aim to minimize muscle and bone loss but also vigilance as regards the development of sarcopenic obesity – a combination of an unhealthy excess of body fat with a detrimental loss of muscle and fat-free mass including bone – is important in the elderly, who are vulnerable to this outcome. Life-style intervention should be the first step and consists of a diet with a 500 kcal (2.1 MJ) energy deficit and an adequate intake of protein of high biological quality together with calcium and vitamin D, behavioural therapy and multi-component exercise. Multi-component exercise includes flexibility training, balance training, aerobic exercise and resistance training. The adherence rate in most studies is around 75%. Knowledge of constraints and modulators of physical inactivity should be of help to engage the elderly in physical activity. The role of pharmacotherapy and bariatric surgery in the elderly is largely unknown as in most studies people aged 65 years and older have been excluded.

Maintained intentional weight loss reduces cardiovascular outcomes: results from the Sibutramine Cardiovascular OUTcomes (SCOUT) trial.

Aim: The Sibutramine Cardiovascular OUTcomes trial showed that sibutramine produced greater mean weight loss than placebo but increased cardiovascular morbidity but not mortality. The relationship between 12‐month weight loss and subsequent cardiovascular outcomes is explored.

Inter-disciplinary European guidelines on surgery of severe obesity.

In 2005, for the first time in European history, an extraordinary Expert panel named ‘The BSCG’ (Bariatric Scientific Collaborative Group), was appointed through joint effort of the major European Scientific Societies which are active in the field of obesity management. Societies that constituted this panel were: IFSO – International Federation for the Surgery of Obesity, IFSO-EC – International Federation for the Surgery of Obesity – European Chapter, EASO – European Association for Study of Obesity, ECOG – European Childhood Obesity Group, together with the IOTF (International Obesity Task Force) which was represented during the completion process by its representative. The BSCG was composed not only of the top officers representing the respective Scientific Societies (four acting presidents, two past presidents, one honorary president, two executive directors), but was balanced with the presence of many other key opinion leaders in the field of obesity. The BSCG composition allowed the coverage of key disciplines in comprehensive obesity management, as well as reflecting European geographical and ethnic diversity. This joint BSCG expert panel convened several meetings which were entirely focused on guidelines creation, during the past two years. There was a specific effort to develop clinical guidelines, which will reflect current knowledge, expertize and evidence based data on morbid obesity treatment.

Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and difficult to treat arterial hypertension.

Obese patients are prone to arterial hypertension, require more antihypertensive medications, and have an increased risk of treatment-resistant arterial hypertension. Obesity-induced neurohumoral activation appears to be involved. The association between obesity and hypertension shows large inter-individual variability, likely through genetic mechanisms. Obesity affects overall cardiovascular and metabolic risk; yet, the relationship between obesity and cardiovascular risk is complex and not sufficiently addressed in clinical guidelines. The epidemiological observation that obesity may be protective in patients with established cardiovascular disease is difficult to translate into clinical experience and practice. Weight loss is often recommended as a means to lower blood pressure. However, current hypertension guidelines do not provide evidence-based guidance on how to institute weight loss. In fact, weight loss influences on blood pressure may be overestimated. Nevertheless, weight loss through bariatric surgery appears to decrease cardiovascular risk in severely obese patients. Eventually, most obese hypertensive patients will require antihypertensive medications. Data from large-scale studies with hard clinical endpoints on antihypertensive medications specifically addressing obese patients are lacking and the morbidity from the growing population of severely obese patients is poorly recognized or addressed. Because of their broad spectrum of beneficial effects, renin-angiotensin system inhibitors are considered to be the most appropriate drugs for antihypertensive treatment of obese patients. Most obese hypertensive patients require two or more antihypertensive drugs. Finally, how to combine weight loss strategies and antihypertensive treatment to achieve an optimal clinical outcome is unresolved.

Validation of a quantitative magnetic resonance method for measuring human body composition.

Objective: To evaluate a novel quantitative magnetic resonance (QMR) methodology (EchoMRI‐AH, Echo Medical Systems) for measurement of whole‐body fat and lean mass in humans.

Interdisciplinary European guidelines on surgery of severe obesity.

In 2005, for the first time in European history, an extraordinary expert panel named BSCG (Bariatric Scientific Collaborative Group), was appointed through joint effort of the major European scientific societies which are active in the field of obesity management. Societies that constituted this panel were: IFSO – International Federation for the Surgery of Obesity, IFSO-EC – International Federation for the Surgery of Obesity – European Chapter, EASO – European Association for Study of Obesity, ECOG – European Childhood Obesity Group, together with the IOTF (International Obesity Task Force) which was represented during the completion process by its representative. The BSCG was composed not only of the top officers representing the respective scientific societies (four acting presidents, two past presidents, one honorary president, two executive directors), but was balanced with the presence of many other key opinion leaders in the field of obesity. The BSCG composition allowed the coverage of key disciplines in comprehensive obesity management, as well as reflecting European geographical and ethnic diversity. This joint BSCG expert panel convened several meetings which were entirely focused on guidelines creation, during the past 2 years. There was a specific effort to develop clinical guidelines, which will reflect current knowledge, expertise and evidence based data on morbid obesity treatment.

Empowering primary care to tackle the obesity epidemic: the Counterweight Programme.

Objective:To improve the management of obese adults (18–75 y) in primary care.Design:Cohort study.Settings:UK primary care.Subjects:Obese patients (body mass index ≥30 kg/m2) or BMI≥28 kg/m2 with obesity-related comorbidities in 80 general practices.Intervention:The model consists of four phases: (1) audit and project development, (2) practice training and support, (3) nurse-led patient intervention, and (4) evaluation. The intervention programme used evidence-based pathways, which included strategies to empower clinicians and patients. Weight Management Advisers who are specialist obesity dietitians facilitated programme implementation.Main outcome measures:Proportion of practices trained and recruiting patients, and weight change at 12 months.Results:By March 2004, 58 of the 62 (93.5%) intervention practices had been trained, 47 (75.8%) practices were active in implementing the model and 1549 patients had been recruited. At 12 months, 33% of patients achieved a clinically meaningful weight loss of 5% or more. A total of 49% of patients were classed as ‘completers’ in that they attended the requisite number of appointments in 3, 6 and 12 months. ‘Completers’ achieved more successful weight loss with 40% achieving a weight loss of 5% or more at 12 months.Conclusion:The Counterweight programme provides a promising model to improve the management of obesity in primary care.Sponsorship:Educational grant-in-aid from Roche Products Ltd.Objective:To improve the management of obese adults (18–75 y) in primary care.Design:Cohort study.Settings:UK primary care.Subjects:Obese patients (body mass index ≥30 kg/m2) or BMI≥28 kg/m2 with obesity-related comorbidities in 80 general practices.Intervention:The model consists of four phases: (1) audit and project development, (2) practice training and support, (3) nurse-led patient intervention, and (4) evaluation. The intervention programme used evidence-based pathways, which included strategies to empower clinicians and patients. Weight Management Advisers who are specialist obesity dietitians facilitated programme implementation.Main outcome measures:Proportion of practices trained and recruiting patients, and weight change at 12 months.Results:By March 2004, 58 of the 62 (93.5%) intervention practices had been trained, 47 (75.8%) practices were active in implementing the model and 1549 patients had been recruited. At 12 months, 33% of patients achieved a clinically meaningful weight loss of 5% or more. A total of 49% of patients were classed as ‘completers’ in that they attended the requisite number of appointments in 3, 6 and 12 months. ‘Completers’ achieved more successful weight loss with 40% achieving a weight loss of 5% or more at 12 months.Conclusion:The Counterweight programme provides a promising model to improve the management of obesity in primary care.Sponsorship:Educational grant-in-aid from Roche Products Ltd.