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This mixed-methods study aimed to explore factors contributing to therapeutic inertia among people living with obesity in Canada from the perspective of general/family practitioners (GP/FPs). One-on-one interviews and online surveys guided by the Theoretical Domains Framework were conducted. A total of 20 general/family practitioners were interviewed and 200 general/family practitioners were surveyed. Key findings from interviews were used to guide the development of the survey. Spearman's correlation analysis evaluated the association between general/family practitioners theme domain scores and their familiarity with the 2020 Canadian Adult Obesity Clinical Practice Guidelines. The 200 general/family practitioners surveyed provided representation across Canada, with diversity in age, background, and gender. The most prominent domains related to therapeutic inertia that were positively influenced by familiarity with Clinical Practice Guidelines were Beliefs about Capabilities (rs = .27; p < .01), Skills (rs = .23; p < .01), Behavioural Regulation (rs = .24; p < .01) and Emotions (rs = .23; p < .01). Irrespective of their familiarity with Clinical Practice Guidelines, most general/family practitioners reported that environmental and contextual barriers impact obesity management. Particularly, while financial barriers were reported by participants regardless of Clinical Practice Guidelines familiarity, general/family practitioners familiar with Clinical Practice Guidelines more often reported having time to discuss obesity management with patients. This study identified perceptions, resource and training considerations that contribute to healthcare decision-making and therapeutic inertia in obesity management among general/family practitioners and highlighted key areas to target with interventions in primary care to facilitate obesity management, which should be multi-faceted, with a focus on incorporating obesity education into healthcare providers training programs and improving systemic and financial support.
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BACKGROUND: There are currently limited data regarding the effect of semaglutide 2·4 mg in individuals with obesity and prediabetes in clinical trials. We aimed to assess the efficacy and safety of semaglutide 2·4 mg for weight management and glycaemic control in participants with obesity and prediabetes. METHODS: STEP 10 was a randomised, double-blind, parallel-group, phase 3 trial done across 30 trial sites in Canada, Denmark, Finland, Spain, and the UK and included participants aged 18 years or older with a BMI of 30 kg/m2 or higher and prediabetes according to UK National Institute for Health and Care Excellence criteria (defined as having at least one of the following at screening: HbA1c of 6·0-6·4% [42-47 mmol/mol] or fasting plasma glucose [FPG] of 5·5-6·9 mmol/L). Participants were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2·4 mg or placebo with diet and physical activity counselling for 52 weeks, followed by a 28-week off-treatment period. Primary endpoints were percentage change in bodyweight and proportion of participants reverting to normoglycaemia (HbA1c <6·0% [<42 mmol/mol] and FPG <5·5 mmol/L) at week 52 (assessed in all randomly assigned participants by intention to treat). Selective safety data were collected for participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT05040971, and is complete. FINDINGS: Between Sept 16 and Dec 29, 2021, 138 participants were randomly assigned to semaglutide 2·4 mg and 69 to placebo. 147 (71%) were female and 60 (29%) were male; 183 (88%) were White. All randomly assigned participants received at least one dose of study drug. Baseline mean age was 53 years (SD 11), bodyweight 111·6 kg (22·2), BMI 40·1 kg/m2 (6·9), waist circumference 120·1 cm (14·7), HbA1c 5·9% (0·3; 41·3 mmol/mol [3·0]), and FPG 5·9 mmol/L (0·6). There was a significantly greater reduction in bodyweight with semaglutide 2·4 mg than with placebo at week 52 (-13·9% [SD 0·7] vs -2·7% [0·6]; estimated treatment difference -11·2% [95% CI -13·0 to -9·4]; p<0·0001). Greater proportions of participants reverted to normoglycaemia at week 52 with semaglutide 2·4 mg than with placebo (103 [81%] of 127 vs nine [14%] of 64; odds ratio 19·8 [95% CI 8·7 to 45·2]; p<0·0001). Serious adverse events occurred in 12 (9%) participants receiving semaglutide 2·4 mg versus six (9%) receiving placebo. Adverse events leading to treatment discontinuation occurred in eight (6%) participants in the semaglutide 2·4 mg group versus one (1%) participant in the placebo group. No new safety signals were reported. INTERPRETATION: Semaglutide 2·4 mg provided superior reduction in bodyweight and reversion to normoglycaemia versus placebo in participants with obesity and prediabetes. The safety and tolerability profile was consistent with previous studies and with the GLP-1 receptor agonist class. These findings support the potential use of semaglutide 2·4 mg as a treatment option for individuals with obesity and prediabetes to achieve reversion to normoglycaemia. FUNDING: Novo Nordisk. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.
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Péptidos Similares al Glucagón , Obesidad , Estado Prediabético , Humanos , Masculino , Femenino , Método Doble Ciego , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Persona de Mediana Edad , Estado Prediabético/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Adulto , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Glucemia/análisis , Glucemia/efectos de los fármacos , Resultado del Tratamiento , Anciano , Pérdida de Peso/efectos de los fármacosRESUMEN
BACKGROUND: Chronic kidney disease (CKD) poses a substantial burden to individuals, caregivers, and healthcare systems. CKD is associated with higher risk for adverse events, including renal failure, cardiovascular disease, and death. This study aims to describe comorbidities and complications in patients with CKD. METHODS: We conducted a retrospective observational study linking administrative health databases in Alberta, Canada. Adults with CKD were identified (April 1, 2010 and March 31, 2019) and indexed on the first diagnostic code or laboratory test date meeting the CKD algorithm criteria. Cardiovascular, renal, diabetic, and other comorbidities were described in the two years before index; complications were described for events after index date. Complications were stratified by CKD stage, atherosclerotic cardiovascular disease (ASCVD), and type 2 diabetes mellitus (T2DM) status at index. RESULTS: The cohort included 588,170 patients. Common chronic comorbidities were hypertension (36.9%) and T2DM (24.1%), while 11.4% and 2.6% had ASCVD and chronic heart failure, respectively. Common acute complications were infection (58.2%) and cardiovascular hospitalization (24.4%), with rates (95% confidence interval [CI]) of 29.4 (29.3-29.5) and 8.37 (8.32-8.42) per 100 person-years, respectively. Common chronic complications were dyslipidemia (17.3%), anemia (14.7%), and hypertension (11.1%), with rates (95% CI) of 11.9 (11.7-12.1), 4.76 (4.69-4.83), and 13.0 (12.8-13.3) per 100 person-years, respectively. Patients with more advanced CKD, ASCVD, and T2DM at index exhibited higher complication rates. CONCLUSIONS: Over two-thirds of patients with CKD experienced complications, with higher rates observed in those with cardio-renal-metabolic comorbidities. Strategies to mitigate risk factors and complications can reduce patient burden.
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Comorbilidad , Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/epidemiología , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Alberta/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Hipertensión/epidemiología , Adulto , Anciano de 80 o más Años , Enfermedades Cardiovasculares/epidemiología , Enfermedad Aguda , Aterosclerosis/epidemiología , HospitalizaciónRESUMEN
OBJECTIVES: This study aimed to assess the cost-effectiveness of weight-management pharmacotherapies approved by Canada Health, i.e., orlistat, naltrexone 32 mg/bupropion 360 mg (NB-32), liraglutide 3.0 mg and semaglutide 2.4 mg as compared to the current standard of care (SoC). METHODS: Analyses were conducted using a cohort with a mean starting age 50 years, body mass index (BMI) 37.5 kg/m2, and 27.6% having type 2 diabetes. Using treatment-specific changes in surrogate endpoints from the STEP trials (BMI, glycemic, blood pressure, lipids), besides a network meta-analysis, the occurrence of weight-related complications, costs, and quality-adjusted life-years (QALYs) were projected over lifetime. RESULTS: From a societal perspective, at a willingness-to-pay (WTP) threshold of CAD 50 000 per QALY, semaglutide 2.4 mg was the most cost-effective treatment, at an incremental cost-utility ratio (ICUR) of CAD 31 243 and CAD 29 014 per QALY gained versus the next best alternative, i.e., orlistat, and SoC, respectively. Semaglutide 2.4 mg extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg and remained cost-effective both under a public and private payer perspective. Results were robust to sensitivity analyses varying post-treatment catch-up rates, longer treatment durations and using real-world cohort characteristics. Semaglutide 2.4 mg was the preferred intervention, with a likelihood of 70% at a WTP threshold of CAD 50 000 per QALY gained. However, when the modeled benefits of weight-loss on cancer, mortality, cardiovascular disease (CVD) or osteoarthritis surgeries were removed simultaneously, orlistat emerged as the best value for money compared with SoC, with an ICUR of CAD 35 723 per QALY gained. CONCLUSION: Semaglutide 2.4 mg was the most cost-effective treatment alternative compared with D&E or orlistat alone, and extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg. Results were sensitive to the inclusion of the combined benefits of mortality, cancer, CVD, and knee osteoarthritis.
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Fármacos Antiobesidad , Análisis Costo-Beneficio , Obesidad , Orlistat , Humanos , Canadá , Persona de Mediana Edad , Obesidad/tratamiento farmacológico , Obesidad/economía , Femenino , Fármacos Antiobesidad/uso terapéutico , Fármacos Antiobesidad/economía , Masculino , Orlistat/uso terapéutico , Años de Vida Ajustados por Calidad de Vida , Liraglutida/uso terapéutico , Liraglutida/economía , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/economía , Bupropión/uso terapéutico , Bupropión/economía , Naltrexona/uso terapéutico , Naltrexona/economía , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/economíaRESUMEN
AIMS: To identify and better understand themes related to why people living with obesity (PwO) in Canada may not use professional support and to explore potential strategies to address the challenges. METHODS: One-on-one interviews and online surveys, informed by the Theoretical Domains Framework, were conducted. A total of 20 PwO were interviewed and a separate group of 200 PwO were surveyed. Results from the interviews guided the development of the survey. Spearman's correlation analysis was performed to investigate the association between the theme domain scores of the PwO and their prior experience with obesity management strategies. RESULTS: The 200 PwO surveyed provided representation across Canada and were diverse in age, background and gender. The most prominent domains associated with use of professional support by PwO were: Intention (rs = -0.25; p < 0.01); Social/Professional Role and Identity (rs = -0.15; p < 0.05); and Optimism (rs = -0.15; p < 0.05). For example, PwO without professional support less often reported being transparent in obesity discussions, perceived obesity to be part of their identity, and expected to manage the illness long term. Many PwO hesitated to use various adjunctive therapies due to concerns about affordability, long-term effectiveness, and side effects. CONCLUSION: This study identified contextual, perception and resource considerations that contribute to healthcare decision-making and the use by PwO of professional support to manage obesity, and highlighted key areas to target with interventions to facilitate obesity management. Strategies such as consistent access to healthcare support and educational resources, as well as improved financial support may help PwO to feel more comfortable with exploring new strategies and take control of their healthcare.
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Manejo de la Obesidad , Humanos , Obesidad/epidemiología , Obesidad/terapia , Canadá/epidemiología , Atención a la Salud , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease and a leading cause of morbidity/mortality in Canada. We evaluated the burden of T2DM in Alberta, Canada, by estimating the 5-year period prevalence of T2DM and rates of comorbidities and complications/conditions after T2DM. METHODS: We conducted a population-based, retrospective study linking administrative health databases. Individuals with T2DM (≥18 years of age) were identified between 2008-2009 and 2018-2019 using a published algorithm, with follow-up data to March 2020. The 5-year period prevalence was estimated for 2014-2015 to 2018-2019. Individuals with newly identified T2DM, ascertained between 2010-2011 and 2017-2018 with a lookback period between 2008-2009 and 2009-2010 and a minimum 1 year of follow-up data, were evaluated for subsequent cardiovascular, diabetic, renal, and other complication/condition frequencies (%) and rates (per 100 person-years). Complications/conditions were stratified by atherosclerotic cardiovascular disease (ASCVD) status at index and age. RESULTS: The 5-year period prevalence of T2DM was 11,051 per 100,000 persons, with the highest prevalence in men 65 to <75 years of age. There were 195,102 individuals included in the cohort (mean age 56.7±14.7 years). The most frequently reported complications/conditions (rates per 100 person-years) were acute infection (23.10, 95% confidence interval [CI] 23.00 to 23.30), hypertension (17.30, 95% CI 16.80 to 17.70), and dyslipidemia (12.20, 95% CI 11.90 to 12.40). Individuals who had an ASCVD event/procedure and those ≥75 years of age had higher rates of complications/conditions. CONCLUSIONS: We found that over half of the individuals had hypertension or infection after T2DM. Also, those with ASCVD had higher rates of complications/conditions. Strategies to mitigate complications/conditions after T2DM are required to reduce the burden of this disease on individuals and health-care systems.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Prevalencia , Alberta/epidemiología , Anciano , Adulto , Complicaciones de la Diabetes/epidemiología , Estudios de Seguimiento , Bases de Datos Factuales , Comorbilidad , Adulto JovenRESUMEN
INTRODUCTION: The recent approval in the USA (Food and Drug Administration), Canada (Health Canada), UK (Medicines and Healthcare products Regulatory Agency), and EU (European Medicines Agency) of once-weekly injectable semaglutide 2.4 mg, as an adjunct to a calorie-controlled diet and increased physical activity, for chronic weight management provides health-care practitioners with an additional option when prescribing weight-loss medication. AREAS COVERED: We describe the chemistry, mechanism of action, and pharmacological properties of semaglutide (a glucagon-like peptide 1 receptor agonist [GLP-1 RA]) and discuss clinical data and considerations for using once-weekly subcutaneous semaglutide 2.4 mg as treatment for overweight and obesity among patients with and without type 2 diabetes (T2D). EXPERT OPINION: Once-weekly subcutaneous semaglutide 2.4 mg is the most efficacious medication approved for chronic weight management among patients with overweight and obesity, with and without T2D, and is the first drug to induce sustained double-digit reductions in percentage body weight over 1- to 2-year treatment periods. It demonstrates a similar safety and tolerability profile to other GLP-1 RAs. Semaglutide 2.4 mg treatment could dramatically improve clinical approaches to weight management, but the relatively high cost might prevent patients accessing treatment. Further research exploring the cost-effectiveness of subcutaneous semaglutide 2.4 mg is required.
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Péptidos Similares al Glucagón , Obesidad , Sobrepeso , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos Similares al Glucagón/farmacología , Péptidos Similares al Glucagón/uso terapéutico , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Obesidad/tratamiento farmacológico , Sobrepeso/inducido químicamente , Sobrepeso/tratamiento farmacológico , Preparaciones FarmacéuticasRESUMEN
BACKGROUND: Natural amylin is a pancreatic hormone that induces satiety. Cagrilintide is a long-acting amylin analogue under investigation for weight management. We assessed the dose-response relationship of cagrilintide regarding the effects on bodyweight, safety, and tolerability. METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial at 57 sites including hospitals, specialist clinics, and primary care centres in ten countries (Canada, Denmark, Finland, Ireland, Japan, Poland, Serbia, South Africa, the UK, and the USA). Eligible participants were adults aged at least 18 years without diabetes, with a body-mass index of at least 30 kg/m2 or at least 27 kg/m2 with hypertension or dyslipidaemia. Participants were randomly assigned (6:1) to subcutaneous self-injections of once-weekly cagrilintide (0·3, 0·6, 1·2, 2·4, or 4·5 mg), once-daily liraglutide 3·0 mg, or volume-matched placebo (for six placebo groups). The trial had a 26-week treatment period, including a dose-escalation period of up to 6 weeks, and a 6-week follow-up period without treatment. Participants and investigators were masked to the assigned study treatment with respect to active versus pooled placebo treatment, but not to different active treatments. The primary endpoint was the percentage change in bodyweight from baseline to week 26, assessed in all randomly assigned participants according to the trial product estimand (assuming all participants were adherent to treatment) and to the treatment policy estimand (regardless of adherence to treatment). Safety was assessed in all participants who received at least one dose of randomised treatment. This trial is registered with ClinicalTrials.gov, NCT03856047, and is closed to new participants. FINDINGS: Between March 1 and Aug 19, 2019, we randomly assigned 706 participants to cagrilintide 0·3-4·5 mg (100-102 per dose group), 99 to liraglutide 3·0 mg, and 101 to placebo. Permanent treatment discontinuation (n=73 [10%]) occurred similarly across treatment groups, mostly due to adverse events (n=30 [4%]). In total, 29 participants (4%) withdrew from the trial. According to the trial product estimand, mean percentage weight reductions from baseline were greater with all doses of cagrilintide (0·3-4·5 mg, 6·0%-10·8% [6·4-11·5 kg]) versus placebo (3·0% [3·3 kg]; estimated treatment difference range 3·0%-7·8%; p<0·001). Weight reductions were also greater with cagrilintide 4·5 mg versus liraglutide 3·0 mg (10·8% [11·5 kg] vs 9·0% [9·6 kg]; estimated treatment difference 1·8%, p=0·03). Similar weight loss reductions were observed with the treatment policy estimand. The most frequent adverse events were gastrointestinal disorders (eg, nausea, constipation, and diarrhoea) and administration-site reactions. More participants receiving cagrilintide 0·3-4·5 mg had gastrointestinal adverse events compared with placebo (41%-63% vs 32%), primarily nausea (20%-47% vs 18%). INTERPRETATION: Treatment with cagrilintide in people with overweight and obesity led to significant reductions in bodyweight and was well tolerated. The findings support the development of molecules with novel mechanisms of action for weight management. FUNDING: Novo Nordisk A/S.
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Relación Dosis-Respuesta a Droga , Polipéptido Amiloide de los Islotes Pancreáticos/uso terapéutico , Obesidad/tratamiento farmacológico , Pérdida de Peso/efectos de los fármacos , África , Índice de Masa Corporal , Método Doble Ciego , Europa (Continente) , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Inyecciones Subcutáneas , Liraglutida/administración & dosificación , Masculino , Persona de Mediana Edad , América del NorteRESUMEN
BACKGROUND: Cagrilintide, a long-acting amylin analogue, and semaglutide 2·4 mg, a glucagon-like peptide-1 analogue, are both being investigated as options for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of this drug combination. METHODS: In this randomised, placebo-controlled, multiple-ascending dose, phase 1b trial, individuals aged 18-55 years with a body-mass index 27·0-39·9 kg/m2 and who were otherwise healthy were recruited from a single centre in the USA. The trial included six sequential overlapping cohorts, and in each cohort eligible participants were randomly assigned (3:1) to once-weekly subcutaneous cagrilintide (0·16, 0·30, 0·60, 1·2, 2·4, or 4·5 mg) or matched placebo, in combination with once-weekly subcutaneous semaglutide 2·4 mg, without lifestyle interventions. In each cohort, the doses of cagrilintide and semaglutide were co-escalated in 4-week intervals to the desired dose over 16 weeks, participants were treated at the target dose for 4 weeks, and then followed up for 5 weeks. Participants, investigators, and the sponsor were masked to treatment assignment. The primary endpoint was number of treatment-emergent adverse events from baseline to end of follow-up. Secondary pharmacokinetic endpoints assessed from day of last dose (week 19) to end of treatment (week 20) were area under the plasma concentration-time curve from 0 to 168 h (AUC0-168 h) and maximum concentration [Cmax] of cagrilintide and semaglutide; exploratory pharmacokinetic endpoints were half-life, time to Cmax [tmax], plasma clearance, and volume of distribution of cagrilintide and semaglutide; and exploratory pharmacodynamic endpoints were changes in bodyweight, glycaemic parameters, and hormones. Safety, pharmacokinetic, and pharmacodynamic endpoints were assessed in all participants who were exposed to at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03600480, and is now complete. FINDINGS: Between July 25, 2018, and Dec 17, 2019, 285 individuals were screened and 96 were randomly assigned to cagrilintide (0·16-2·4 mg group n=12; 4·5 mg group n=11) or placebo (n=24), in combination with semaglutide 2·4 mg, of whom 95 were exposed to treatment (one patient in 0·60 mg cagrilintide group was not exposed) and included in the safety and full analysis datasets. The mean age was 40·6 years (SD 9·2), 56 (59%) of 95 participants were men and 51 (54%) were Black or African American. Of 566 adverse events reported in 92 participants (69 [97%] of 71 participants assigned to 0·16-4·5 mg cagrilintide and 23 [96%] of 24 assigned to placebo), 207 (37%) were gastrointestinal disorders. Most adverse events were mild to moderate in severity and the proportion of participants with one or more adverse event was similar across treatment groups. Exposure was proportional to cagrilintide dose and did not affect semaglutide exposure or elimination. AUC0-168 h ranged from 926 nmol × h/L to 24 271 nmol × h/L, and Cmax ranged from 6·14 nmol/L to 170 nmol/L with cagrilintide 0·16-4·5 mg. AUC0-168 h ranged from 12 757 nmol × h/L to 15 305 nmol × h/L, and Cmax ranged from 96·4 nmol/L to 120 nmol/L with semaglutide 2·4 mg. Cagrilintide 0·16-4·5 mg had a half-life of 159-195 h, with a median tmax of 24-72 h. Semaglutide 2·4 mg had a half-life of 145-165 h, with a median tmax of 12-24 h. Plasma clearance and volume of distribution for both cagrilintide and semaglutide were similar across treatment groups. At week 20, mean percentage bodyweight reductions were greater with cagrilintide 1·2 and 2·4 mg than with placebo (15·7% [SE 1·6] for cagrilintide 1·2 mg and 17·1% [1·5] for cagrilintide 2·4 mg vs 9·8% [1·2] for pooled placebo cohorts 1-5; estimated treatment difference of -6·0% [95% CI -9·9 to -2·0] for cagrilintide 1·2 mg and -7·4% [-11·2 to -3·5] for cagrilintide 2·4 mg vs pooled placebo), and with cagrilintide 4·5 mg than with matched placebo (15·4% [1·3] vs 8·0% [2·2]; estimated treatment difference -7·4% [-12·8 to -2·1]), all in combination with semaglutide 2·4 mg. Glycaemic parameters improved in all treatment groups, independently of cagrilintide dose. Changes in hormones were similar across treatment groups. INTERPRETATION: Concomitant treatment with cagrilintide and semaglutide 2·4 mg was well tolerated with an acceptable safety profile. Future larger and longer trials are needed to fully assess the efficacy and safety of this treatment combination. FUNDING: Novo Nordisk A/S.
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Fármacos Antiobesidad/administración & dosificación , Péptidos Similares al Glucagón/administración & dosificación , Polipéptido Amiloide de los Islotes Pancreáticos/administración & dosificación , Obesidad/tratamiento farmacológico , Pérdida de Peso/efectos de los fármacos , Adulto , Fármacos Antiobesidad/farmacocinética , Fármacos Antiobesidad/farmacología , Método Doble Ciego , Quimioterapia Combinada , Femenino , Péptidos Similares al Glucagón/farmacocinética , Péptidos Similares al Glucagón/farmacología , Humanos , Inyecciones , Polipéptido Amiloide de los Islotes Pancreáticos/efectos adversos , Polipéptido Amiloide de los Islotes Pancreáticos/farmacocinética , Masculino , Persona de Mediana EdadAsunto(s)
Obesidad/terapia , Atención Primaria de Salud/métodos , Adulto , Índice de Masa Corporal , Canadá , Femenino , Humanos , Masculino , EmbarazoRESUMEN
Obesity is a complex chronic disease in which abnormal or excess body fat (adiposity) impairs health, increases the risk of long-term medical complications and reduces lifespan.1 Epidemiologic studies define obesity using the body mass index (BMI; weight/height2), which can stratify obesity-related health risks at the population level. Obesity is operationally defined as a BMI exceeding 30 kg/m2 and is subclassified into class 1 (3034.9), class 2 (3539.9) and class 3 (≥ 40). At the population level, health complications from excess body fat increase as BMI increases.2 At the individual level, complications occur because of excess adiposity, location and distribution of adiposity and many other factors, including environmental, genetic, biologic and socioeconomic factors.
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Humanos , Adulto , Determinantes Sociales de la Salud , Manejo de la Obesidad , Obesidad/terapia , Índice de Masa Corporal , Terapia Nutricional , Estilo de Vida Saludable , Obesidad/complicacionesRESUMEN
Obesity is a complex chronic disease in which abnormal or excess body fat (adiposity) impairs health, increases the risk of long-term medical complications and reduces life span. However, due to individual differences in body composition, body fat distribution and function, the threshold to which adiposity impairs health is highly variable among adults.1 Epidemiological and population studies define obesity using the body mass index (BMI, weight/height2 ). BMI is a fairly reliable anthropometric measurement to stratify obesity-related health risks at the population level. Obesity is operationally defined as a BMI exceeding 30 kg/m2 , and is subclassified into Class I (BMI 3034.9), Class II (BMI 3539.9) and Class III (BMI > 40). Obesity is a chronic disease caused by the complex interplay of genetic, metabolic, behavioural and environmental factors; the latter are thought to be the proximal cause of the dramatic rise in the prevalence of obesity.2 The increased availability of processed, affordable and effectively marketed food, abundance of sugar-sweetened beverages, economic growth, behavioural changes and rapid urbanization in lowand middle-income countries are some of the key drivers that promote overconsumption of food.3 With respect to energy expenditure, the level of physical activity for leisure has been relatively stable or slightly elevated over the last 50 years.4 This chapter attempts to address the cellular and molecular pathogenesis of obesity to inform a rational approach to management of this complex disease.
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Humanos , Obesidad/diagnóstico , Regulación del Apetito , Tejido Adiposo , Factores de Riesgo , CitocinasAsunto(s)
Enfermedades Cardiovasculares/prevención & control , Atención Primaria de Salud , Consumo de Bebidas Alcohólicas/prevención & control , Fumar Cigarrillos/prevención & control , Complicaciones de la Diabetes/prevención & control , Dieta Hiposódica , Dislipidemias/prevención & control , Estilo de Vida Saludable , Humanos , Hipertensión/prevención & control , Obesidad/prevención & control , Medición de RiesgoRESUMEN
This guideline is directed to primary health care providers caring for Canadian adults who have or are at risk of developing chronic cardiovascular diseases, including hypertension, diabetes, dyslipidemia, heart failure and stroke, and the risk factors for these conditions, including smoking, obesity and physical inactivity. The purpose of the C-CHANGE guideline is to bring together a comprehensive set of recommendations drawn from the nine participating guideline groups applicable to the care of people with multiple comorbidities. The aim is also to do this with sufficient rigour that health care practitioners and patients have confidence in the C-CHANGE process, as well as in the guidelines from the nine participating groups.
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Humanos , Atención Primaria de Salud/normas , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/complicaciones , Comorbilidad , Factores de RiesgoAsunto(s)
Diabetes Mellitus , Publicaciones Periódicas como Asunto , Edición , Canadá , Políticas Editoriales , HumanosRESUMEN
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.