Neuropsychiatric safety with liraglutide 3.0 mg for weight management: Results from randomized controlled phase 2 and 3a trials.

AIMS: Liraglutide, a GLP-1 receptor agonist, regulates appetite via receptors in the brain. Because of concerns regarding the potential of centrally-acting anti-obesity medications to affect mental health, pooled neuropsychiatric safety data from all phase 2 and 3a randomized, double-blind trials with liraglutide 3.0 mg were evaluated post hoc. METHODS: Data from the liraglutide weight-management programme were pooled. Across trials, individuals with a body mass index ≥30 or ≥27 kg/m2 with weight-related comorbidities were randomized to once-daily subcutaneous liraglutide 3.0 mg (n = 3384) or placebo (n = 1941), both with a 500 kcal/d deficit diet, plus exercise. Adverse events related to neuropsychiatric safety were collected in all trials. Additionally, in the phase 3a trials, validated mental-health questionnaires were prospectively and systematically administered. RESULTS: In the pooled analysis of 5325 randomized and exposed individuals, rates of depression (2.1 vs 2.1 events/100 person-years) and anxiety (1.9 vs 1.7 events/100 person-years) through adverse event reporting were similarly low in liraglutide and placebo groups. Nine (0.3%) individuals receiving liraglutide and 2 (0.1%) receiving placebo reported adverse events of suicidal ideation or behaviour. In phase 3a trials, mean baseline Patient Health Questionnaire-9 scores of 2.8 ± 3.0 vs 2.9 ± 3.1 for liraglutide vs placebo improved to 1.8 ± 2.7 vs 1.9 ± 2.7, respectively, at treatment end; 34/3291 individuals (1.0%) receiving liraglutide 3.0 mg vs 19/1843 (1.0%) receiving placebo reported suicidal ideation on the Columbia-Suicide Severity Rating Scale. CONCLUSIONS: Results of this exploratory pooled analysis provide no cause for concern regarding the neuropsychiatric safety of treatment with liraglutide 3.0 mg in patients similar to those included in the examined trials. Although there was a small numerical imbalance in suicidal ideation with liraglutide through adverse event reporting, no between-treatment imbalances in suicidal ideation/behaviour or depression were noted through prospective questionnaire assessments.

The impact of COVID-19 on obesity services across Europe: A physician survey.

Obesity is a risk factor for severe complications from coronavirus disease 2019 (COVID-19). During the COVID-19 pandemic in Spring 2020, many clinics and obesity centers across Europe were required to close. This study aimed to determine the impact of COVID-19 on the provision of obesity services across 10 European countries via a survey of physicians (n = 102) specializing in treating persons with obesity (PwO). In total, 62-95 out of 102 physicians reported that COVID-19 affected obesity-related services, with cancellations/suspensions ranging from 50% to 100% across the 10 countries. Approximately 75% of cancellations/suspensions were provider- rather than patient-initiated. A median increase of 20%-25% in waiting times was reported for most services across the countries. When services resume, 87 out of 100 physicians consider factors influencing down-stream patient outcomes as the most relevant factors for prioritizing interventional treatment. Responses showed that 65 out of 102 and 36 out of 102 physicians believed it (highly) likely that a change in treatment guidance will occur to prioritize earlier interventional treatment for the management of PwO, by either using bariatric surgery or pharmacotherapy, respectively. Results from this study provide important learnings, such as opportunities for, and discrepancies in, the provision of alternative care in light of services cancellations or delays, which may be important for the future management of obesity, especially during future waves of COVID-19 or other infectious pandemics.

Attitudes about the treatment of obesity among healthcare providers involved in the care of obesity-related diseases: A survey across medical specialties in multiple European countries.

BACKGROUND AND RATIONALE: Obesity is associated with the development and progression of many diseases. Understanding and management of obesity have become increasingly important; however, a knowledge gap remains between how healthcare providers (HCPs) consider weight-loss treatment and the importance of weight loss for improving obesity-related diseases. OBJECTIVE: The objective of this study was to investigate how HCPs assess obesity, how they interpret the relationship between obesity and 12 recognized co-morbidities of obesity (excluding diabetes), and their view about the value of various weight-loss therapies. METHODS: This was a cross-sectional, non-interventional, descriptive study. Participants were medical doctors (HCPs) from eight European countries. RESULTS: Eighty-nine percent of the 197 HCPs that completed the survey considered obesity a disease. For most of the 12 obesity-related diseases under consideration, a majority of HCPs agreed that weight loss could reverse the disease or prevent progression. Among HCPs who have recommended weight loss, lifestyle interventions were by far the most common recommendation. However, more than three out of four HCPs stated that they would be likely to prescribe anti-obesity medications if available and reimbursed. CONCLUSION: Most HCPs in this survey consider obesity a disease that needs to be treated. However, the majority of HCPs appear to prefer recommending lifestyle changes, although it is well documented that weight loss obtained by lifestyle changes is difficult to maintain. These results underscore the need for improved education of HCPs involved in the treatment of obesity-related diseases.

Costs of the COVID-19 pandemic associated with obesity in Europe: A health-care cost model.

Excess weight is associated with severe outcomes of coronavirus disease 2019 (COVID-19). We aimed to estimate the total secondary care costs by body mass index (BMI, kg/m2 ) category when hospitalized due to COVID-19 in Europe during the first wave of the pandemic from January to June 2020. Building a health-care cost model, this study aimed to estimate the total costs of COVID-19. Information on risk of hospitalization, admission to intensive care unit (ICU) and risk of ventilation were based on published data. Average cost per patient and in total were calculated based on risks of admission to ICU, risk of invasive mechanical ventilation and length of hospital stay when hospitalized and published costs associated with hospitalization. The total direct costs of secondary care during the first wave of COVID-19 in Europe were estimated at EUR 13.9 billon, whereof 76% accounted for treating people with overweight and obesity. The average cost per hospital admission increased with BMI, from EUR 15831 for BMI <25 kg/m2 to EUR 30982 for BMI ≥40 kg/m2 . This study reveals that excess weight contributes disproportionally to the costs of COVID-19. This might reflect that overweight and obesity caused the COVID-19 pandemic to result in more severe outcomes for citizens and higher secondary care costs throughout Europe.

Comparison of Efficacy and Safety of Liraglutide 3.0 mg in Individuals with BMI above and below 35 kg/m²: A Post-hoc Analysis.

OBJECTIVE: To investigate whether the efficacy and safety of liraglutide 3.0 mg differed between two subgroups, BMI 27 to <35 and BMI ≥ 35 kg/m², in individuals without and with type 2 diabetes (T2D). METHODS: A post-hoc analysis of two 56-week, randomized, double-blind, placebo-controlled trials (SCALE Obesity and Prediabetes; SCALE Diabetes). Subgroup differences in treatment effects of liraglutide 3.0 mg were evaluated by testing the interaction between treatment group and baseline BMI subgroup. RESULTS: Significantly greater weight loss (0-56 weeks) was observed with liraglutide 3.0 mg versus placebo in all patient groups while on treatment. There was no evidence that the weight-lowering effect of liraglutide 3.0 mg differed between BMI subgroups (interaction p > 0.05). Similarly, for most secondary endpoints significantly greater improvements were observed with liraglutide 3.0 mg versus placebo, with no indication treatment effects differing between subgroups. The safety profile of liraglutide 3.0 mg was broadly similar across BMI subgroups. CONCLUSION: This post-hoc analysis did not indicate any differences in the treatment effects, or safety profile, of liraglutide 3.0 mg for individuals with BMI 27 to <35 or ≥35 kg/m². Liraglutide 3.0 mg can therefore be considered for individuals with a BMI of ≥35 as well as for those with a BMI of 27 to <35 kg/m².