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Background: This joint clinical perspective by the Obesity Medicine Association (OMA) and Obesity Action Coalition (OAC) provides clinicians an overview of the role of advocacy in improving the lives of patients living with the disease of obesity, as well as describes opportunities how to engage in advocacy. Methods: This joint clinical perspective is based upon scientific evidence, clinical experiences of the authors, and peer review by the OMA leadership. The Obesity Medicine Association is the largest organization of physicians, nurse practitioners, physician associates, and other clinical experts (i.e., over 5000 members at time of print) who are engaged in improving the lives of patients affected by the disease of obesity. The OAC is a national nonprofit organization of more than 80,000 members who are dedicated to serving the needs of individuals living with obesity. Results: Advocacy involves educational and public policy initiatives that through relationships, networks, and targeted strategies and tactics (e.g., traditional media, social media, petitions, and direct communication with policy makers), promote public awareness and establish public policies that help mitigate bias, stigma, and discrimination, and generally improve the lives of patients living with the disease of obesity. Conclusions: An objective of advocacy is to foster collective involvement and community engagement, leading to collaborations that help empower patients living with obesity and their clinicians to seek and achieve changes in policy, environment, and societal attitudes. Advocacy may also serve to enhance public awareness, promote prevention, advance clinical research, develop safe and effective evidenced-based therapeutic interventions, and facilitate patient access to comprehensive and compassionate treatment of the complex disease of obesity.
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Background: This joint expert review by the Obesity Medicine Association (OMA) and National Lipid Association (NLA) provides clinicians an overview of the pathophysiologic and clinical considerations regarding obesity, dyslipidemia, and cardiovascular disease (CVD) risk. Methods: This joint expert review is based upon scientific evidence, clinical perspectives of the authors, and peer review by the OMA and NLA leadership. Results: Among individuals with obesity, adipose tissue may store over 50% of the total body free cholesterol. Triglycerides may represent up to 99% of lipid species in adipose tissue. The potential for adipose tissue expansion accounts for the greatest weight variance among most individuals, with percent body fat ranging from less than 5% to over 60%. While population studies suggest a modest increase in blood low-density lipoprotein cholesterol (LDL-C) levels with excess adiposity, the adiposopathic dyslipidemia pattern most often described with an increase in adiposity includes elevated triglycerides, reduced high density lipoprotein cholesterol (HDL-C), increased non-HDL-C, elevated apolipoprotein B, increased LDL particle concentration, and increased small, dense LDL particles. Conclusions: Obesity increases CVD risk, at least partially due to promotion of an adiposopathic, atherogenic lipid profile. Obesity also worsens other cardiometabolic risk factors. Among patients with obesity, interventions that reduce body weight and improve CVD outcomes are generally associated with improved lipid levels. Given the modest improvement in blood LDL-C with weight reduction in patients with overweight or obesity, early interventions to treat both excess adiposity and elevated atherogenic cholesterol (LDL-C and/or non-HDL-C) levels represent priorities in reducing the risk of CVD.
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[This corrects the article DOI: 10.1016/j.obpill.2022.100044.].
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BACKGROUND: This joint expert review by the Obesity Medicine Association (OMA) and National Lipid Association (NLA) provides clinicians an overview of the pathophysiologic and clinical considerations regarding obesity, dyslipidemia, and cardiovascular disease (CVD) risk. METHODS: This joint expert review is based upon scientific evidence, clinical perspectives of the authors, and peer review by the OMA and NLA leadership. RESULTS: Among individuals with obesity, adipose tissue may store over 50% of the total body free cholesterol. Triglycerides may represent up to 99% of lipid species in adipose tissue. The potential for adipose tissue expansion accounts for the greatest weight variance among most individuals, with percent body fat ranging from less than 5% to over 60%. While population studies suggest a modest increase in blood low-density lipoprotein cholesterol (LDL-C) levels with excess adiposity, the adiposopathic dyslipidemia pattern most often described with an increase in adiposity includes elevated triglycerides, reduced high-density lipoprotein cholesterol (HDL-C), increased non-HDL-C, elevated apolipoprotein B, increased LDL particle concentration, and increased small, dense LDL particles. CONCLUSIONS: Obesity increases CVD risk, at least partially due to promotion of an adiposopathic, atherogenic lipid profile. Obesity also worsens other cardiometabolic risk factors. Among patients with obesity, interventions that reduce body weight and improve CVD outcomes are generally associated with improved lipid levels. Given the modest improvement in blood LDL-C with weight reduction in patients with overweight or obesity, early interventions to treat both excess adiposity and elevated atherogenic cholesterol (LDL-C and/or non-HDL-C) levels represent priorities in reducing the risk of CVD.
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Enfermedades Cardiovasculares , Dislipidemias , Obesidad , Humanos , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Dislipidemias/sangre , Dislipidemias/complicaciones , Obesidad/complicaciones , Sociedades Médicas , Factores de RiesgoRESUMEN
AIM: To evaluate the equivalence of immunogenicity, safety and efficacy of Gan & Lee (GL) Glargine (Basalin®; Gan & Lee Pharmaceutical) with that of the reference product (Lantus®) in adult participants with type 2 diabetes mellitus. METHODS: This was a phase 3, multicenter, open-label, equivalence trial conducted across 57 sites. In total, 567 participants with type 2 diabetes mellitus were randomized in a 1:1 ratio to undergo treatment with either GL Glargine or Lantus® for 26 weeks. The primary endpoint was the proportion of participants in each treatment arm who manifested treatment-induced anti-insulin antibodies (AIA). Secondary endpoints included efficacy and safety metrics, changes in glycated haemoglobin levels, and a comparative assessment of adverse events. Results were analysed using an equivalence test comparing the limits of the 90% confidence interval (CI) for treatment-induced AIA development to the prespecified margins. RESULTS: The percentages of participants positive for treatment-induced glycated haemoglobin by week 26 were similar between the GL Glargine (19.2%) and Lantus® (21.3%) treatment groups, with a treatment difference of -2.1 percentage points and a 90% CI (-7.6%, 3.5%) (predefined similarity margins: -10.7%, 10.7%). The difference in glycated haemoglobin was -0.08% (90% CI, -0.23, 0.06). The overall percentage of participants with any treatment-emergent adverse events was similar between the GL Glargine (80.1%) and Lantus® (81.6%) treatment groups. CONCLUSIONS: GL Glargine was similar to Lantus® in terms of immunogenicity, efficacy, and safety, based on the current study.
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Biosimilares Farmacéuticos , Diabetes Mellitus Tipo 2 , Hemoglobina Glucada , Hipoglucemiantes , Insulina Glargina , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/efectos adversos , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/inmunología , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/análisis , Hipoglucemia/inducido químicamente , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Anticuerpos Insulínicos/sangre , Insulina Glargina/uso terapéutico , Insulina Glargina/efectos adversos , Equivalencia Terapéutica , Resultado del TratamientoRESUMEN
Background: A fixed-dose combination of phentermine and extended-release topiramate (PHEN/TPM - approved for weight management) has demonstrated in-clinic reduction of blood pressure (BP). Ambulatory BP monitoring (ABPM) may be a better predictor of cardiovascular disease risk than in-clinic BP. Methods: This randomized, multicenter, double-blind study enrolled 565 adults with overweight/obesity. Inclusion criteria included participants willing to wear ABPM device for 24 h. Exclusion criteria included screening blood pressure >140/90 mmHg and antihypertensive medications not stable for 3 months prior to randomization. Participants received placebo (n = 184), phentermine 30 mg; (n = 191), or PHEN 15 mg/TPM 92 mg; (n = 190). 24-hour ABPM was performed at baseline and at week 8. The primary endpoint was mean 24-h systolic BP (SBP) as measured by ABPM, in the per protocol population. Results: Participants were mostly female (73.5 â%) and White (81.6 â%), with a mean age of 53.4 years; 32.4 â% had no hypertension diagnosis or treatment, 62.5 â% had hypertension using 0 to 2 antihypertensive medications, and 5.1 â% had hypertension using ≥ 3 antihypertensive medications. Baseline mean SBP/diastolic BP (DBP) was 123.9/77.6 âmmHg. At week 8, mean SBP change was -0.1 âmmHg (placebo), +1.4 âmmHg (phentermine 30 âmg), and -3.3 âmmHg (PHEN/TPM). Between-group difference for PHEN/TPM versus placebo was -3.2 âmmHg (95 â% CI: -5.48, -0.93 âmmHg; p â= â0.0059). The between-group difference for PHEN/TPM versus phentermine 30 âmg was -4.7 âmmHg (95 â% CI: -6.96, -2.45 âmmHg; p â< â0.0001). Common (>2 â% in any treatment group) adverse events (i.e., dry mouth, constipation, nausea, dizziness, paresthesia, dysgeusia, headache, COVID-19, urinary tract infection, insomnia, and anxiety) were mostly mild or moderate. Conclusions: In this randomized, multicenter, double-blind ABPM study, PHEN/ TPM reduced SBP compared to either placebo or phentermine 30 mg (Funding: Vivus LLC; ClinicalTrials.gov: NCT05215418).
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BACKGROUND: Bempedoic acid is an oral adenosine triphosphate citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) blood levels. The Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes study demonstrated that bempedoic acid reduced cardiovascular (CV) risk in patients at high risk for CV events who were unwilling or unable to take guideline-recommended doses of statins. OBJECTIVE: To describe detailed safety information from CLEAR Outcomes, including events in the United States (US) prescribing information based on previous phase 3 hyperlipidemia studies. METHODS: CLEAR Outcomes was a double-blind trial conducted in 13,970 patients randomized to oral bempedoic acid 180 mg daily or placebo and followed for a median of 3.4 years. RESULTS: In patients who received at least one dose (7,001 bempedoic acid, 6,964 placebo), treatment emergent adverse events (AE) occurred in 86.3 % and 85 % of patients, respectively. COVID-19 was the most frequently reported AE in both groups. Changes in serum creatinine, blood urea nitrogen, hemoglobin, aminotransaminases, and uric acid were consistent with the known safety profile of bempedoic acid. Gout or gouty arthritis occurred in 3.2 % of bempedoic acid and 2.2 % of placebo patients. AE associated with tendinopathies, including tendon rupture, occurred in 2 % of patients in both treatment groups. Cholelithiasis occurred in 2.2 % of bempedoic acid and 1.2 % of placebo patients; AE related to gallbladder disease were similar between treatment groups. CONCLUSIONS: Bempedoic acid was well-tolerated compared with placebo. Safety data from the long-term CLEAR Outcomes study reinforce the positive benefit-risk profile of bempedoic acid.
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Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hipercolesterolemia , Humanos , Enfermedades Cardiovasculares/tratamiento farmacológico , Colesterol , Ácidos Dicarboxílicos/efectos adversos , Ácidos Grasos/uso terapéutico , Factores de Riesgo de Enfermedad Cardiaca , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Factores de Riesgo , Método Doble CiegoRESUMEN
Importance: The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. Objective: To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. Design, Setting, and Participants: This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. Interventions: Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. Main Outcomes and Measures: The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. Results: Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. Conclusions and Relevance: In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. Trial Registration: ClinicalTrials.gov Identifier: NCT04660643.
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Fármacos Antiobesidad , Obesidad , Pérdida de Peso , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Doble Ciego , Polipéptido Inhibidor Gástrico/administración & dosificación , Polipéptido Inhibidor Gástrico/efectos adversos , Polipéptido Inhibidor Gástrico/farmacología , Polipéptido Inhibidor Gástrico/uso terapéutico , Obesidad/tratamiento farmacológico , Obesidad/complicaciones , Sobrepeso/complicaciones , Sobrepeso/tratamiento farmacológico , Resultado del Tratamiento , Pérdida de Peso/efectos de los fármacos , Receptor del Péptido 2 Similar al Glucagón/administración & dosificación , Receptor del Péptido 2 Similar al Glucagón/agonistas , Receptor del Péptido 2 Similar al Glucagón/uso terapéutico , Incretinas/administración & dosificación , Incretinas/efectos adversos , Incretinas/farmacología , Incretinas/uso terapéutico , Fármacos Antiobesidad/administración & dosificación , Fármacos Antiobesidad/efectos adversos , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico , Quimioterapia de Mantención , Inyecciones Subcutáneas , Privación de TratamientoRESUMEN
Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) provides an overview of the mechanisms and treatment of obesity and hypertension. Methods: The scientific support for this CPS is based upon published citations, clinical perspectives of OMA authors, and peer review by the Obesity Medicine Association leadership. Results: Mechanisms contributing to obesity-related hypertension include unhealthful nutrition, physical inactivity, insulin resistance, increased sympathetic nervous system activity, renal dysfunction, vascular dysfunction, heart dysfunction, increased pancreatic insulin secretion, sleep apnea, and psychosocial stress. Adiposopathic factors that may contribute to hypertension include increased release of free fatty acids, increased leptin, decreased adiponectin, increased renin-angiotensin-aldosterone system activation, increased 11 beta-hydroxysteroid dehydrogenase type 1, reduced nitric oxide activity, and increased inflammation. Conclusions: Increase in body fat is the most common cause of hypertension. Among patients with obesity and hypertension, weight reduction via healthful nutrition, physical activity, behavior modification, bariatric surgery, and anti-obesity medications mostly decrease blood pressure, with the greatest degree of weight reduction generally correlated with the greatest degree of blood pressure reduction.
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Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) is intended to provide clinicians with an overview on obesity, thrombosis, venous disease, lymphatic disease, and lipedema. Methods: The scientific support for this CPS is based upon published citations, clinical perspectives of OMA authors, and peer review by the Obesity Medicine Association leadership. Results: Topics in this CPS include obesity, thrombosis, venous disease, lymphatic disease, and lipedema. Obesity increases the risk of thrombosis and cardiovascular disease via fat mass and adiposopathic mechanisms. Treatment of thrombosis or thrombotic risk includes healthful nutrition, physical activity, and the requisite knowledge of how body weight affects anti-thrombotic medications. In addition to obesity-related thrombotic considerations of acute coronary syndrome and ischemic non-hemorrhagic stroke, this Clinical Practice Statement briefly reviews the diagnosis and management of clinically relevant presentations of deep vein thromboses, pulmonary embolism, chronic venous stasis, varicose veins, superficial thrombophlebitis, lipodermatosclerosis, corona phlebectatica, chronic thromboembolic pulmonary hypertension, iliofemoral venous obstruction, pelvic venous disorder, post-thrombotic syndrome, as well as lymphedema and lipedema - which should be included in the differential diagnosis of other edematous or enlargement disorders of the lower extremities. Conclusions: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) on obesity, thrombosis, and venous/lymphatic disease is one of a series of OMA CPSs designed to assist clinicians in the care of patients with the disease of obesity.
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Background: Certification of obesity medicine for physicians in the United States occurs mainly via the American Board of Obesity Medicine (ABOM). Obesity medicine is not recognized as a subspecialty by the American Board of Medical Specialties (ABMS) or the American Osteopathic Association (AOA). This review examines the value of specialization, status of current ABOM Diplomates, governing bodies involved in ABMS/AOA Board Certification, and the advantages and disadvantages of an ABMS/AOA recognized obesity medicine subspecialty. Methods: Data for this review were derived from PubMed and appliable websites. Content was driven by the expertise, insights, and perspectives of the authors. Results: The existing ABOM obesity medicine certification process has resulted in a dramatic increase in the number of Obesity Medicine Diplomates. If ABMS/AOA were to recognize obesity medicine as a subspecialty under an existing ABMS Member Board, then Obesity Medicine would achieve a status like other ABMS recognized subspecialities. However, the transition of ABOM Diplomates to ABMS recognized subspecialists may affect the kinds and the number of physicians having an acknowledged focus on obesity medicine care. Among transition issues to consider include: (1) How many ABMS Member Boards would oversee Obesity Medicine as a subspecialty and which physicians would be eligible? (2) Would current ABOM Diplomates be required to complete an Obesity Medicine Fellowship? If not, then what would be the process for a current ABOM Diplomate to transition to an ABMS-recognized Obesity Medicine subspecialist (i.e., "grandfathering criteria")? and (3) According to the ABMS, do enough Obesity Medicine Fellowship programs exist to recognize Obesity Medicine as a subspecialty? Conclusions: Decisions regarding a transition to an ABMS recognized Obesity Medicine Subspecialty versus retention of the current ABOM Diplomate Certification should consider which best facilitates medical access and care to patients with obesity, and which best helps obesity medicine clinicians be recognized for their expertise.
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Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) provides clinicians an overview of Artificial Intelligence, focused on the management of patients with obesity. Methods: The perspectives of the authors were augmented by scientific support from published citations and integrated with information derived from search engines (i.e., Chrome by Google, Inc) and chatbots (i.e., Chat Generative Pretrained Transformer or Chat GPT). Results: Artificial Intelligence (AI) is the technologic acquisition of knowledge and skill by a nonhuman device, that after being initially programmed, has varying degrees of operations autonomous from direct human control, and that performs adaptive output tasks based upon data input learnings. AI has applications regarding medical research, medical practice, and applications relevant to the management of patients with obesity. Chatbots may be useful to obesity medicine clinicians as a source of clinical/scientific information, helpful in writings and publications, as well as beneficial in drafting office or institutional Policies and Procedures and Standard Operating Procedures. AI may facilitate interactive programming related to analyses of body composition imaging, behavior coaching, personal nutritional intervention & physical activity recommendations, predictive modeling to identify patients at risk for obesity-related complications, and aid clinicians in precision medicine. AI can enhance educational programming, such as personalized learning, virtual reality, and intelligent tutoring systems. AI may help augment in-person office operations and telemedicine (e.g., scheduling and remote monitoring of patients). Finally, AI may help identify patterns in datasets related to a medical practice or institution that may be used to assess population health and value-based care delivery (i.e., analytics related to electronic health records). Conclusions: AI is contributing to both an evolution and revolution in medical care, including the management of patients with obesity. Challenges of Artificial Intelligence include ethical and legal concerns (e.g., privacy and security), accuracy and reliability, and the potential perpetuation of pervasive systemic biases.
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Background: A common adiposopathic complication of obesity is type 2 diabetes mellitus. Healthful weight reduction in patients with obesity can improve glucose metabolism and potentially promote remission of type 2 diabetes mellitus. However, weight-reduction in patients with increased adiposity is impaired among patients with type 2 diabetes mellitus compared to patients without diabetes mellitus. Methods: Data for this review were derived from PubMed and applicable websites. Results: Among patients with increased body fat, the mechanisms underlying impaired weight reduction for those with type 2 diabetes mellitus are multifactorial, and include energy conservation (i.e., improved glucose control and reduced glucosuria), hyperinsulinemia (commonly found in many patients with type 2 diabetes mellitus), potential use of obesogenic anti-diabetes medications, and contributions from multiple body systems. Other factors include increased age, sex, genetic/epigenetic predisposition, and obesogenic environments. Conclusions: Even though type 2 diabetes mellitus impairs weight reduction among patients with increased adiposity, clinically meaningful weight reduction improves glucose metabolism and can sometimes promote diabetes remission. An illustrative approach to mitigate impaired weight reduction due to type 2 diabetes mellitus is choosing anti-diabetes medications that increase insulin sensitivity and promote weight loss and deprioritize use of anti-diabetes medications that increase insulin exposure and promote weight gain.
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Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) is intended to provide clinicians an overview of type 2 diabetes mellitus (T2DM), an obesity-related cardiometabolic risk factor. Methods: The scientific support for this CPS is based upon published citations and clinical perspectives of OMA authors. Results: Topics include T2DM and obesity as cardiometabolic risk factors, definitions of obesity and adiposopathy, and mechanisms for how obesity causes insulin resistance and beta cell dysfunction. Adipose tissue is an active immune and endocrine organ, whose adiposopathic obesity-mediated dysfunction contributes to metabolic abnormalities often encountered in clinical practice, including hyperglycemia (e.g., pre-diabetes mellitus and T2DM). The determination as to whether adiposopathy ultimately leads to clinical metabolic disease depends on crosstalk interactions and biometabolic responses of non-adipose tissue organs such as liver, muscle, pancreas, kidney, and brain. Conclusions: This review is intended to assist clinicians in the care of patients with the disease of obesity and T2DM. This CPS provides a simplified overview of how obesity may cause insulin resistance, pre-diabetes, and T2DM. It also provides an algorithmic approach towards treatment of a patient with obesity and T2DM, with "treat obesity first" as a priority. Finally, treatment of obesity and T2DM might best focus upon therapies that not only improve the weight of patients, but also improve the health outcomes of patients (e.g., cardiovascular disease and cancer).
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Pegozafermin, a long-acting glycopegylated analog of human fibroblast growth factor 21, is in development for the treatment of severe hypertriglyceridemia (SHTG) and nonalcoholic steatohepatitis. Here we report the results of a phase 2, double-blind, randomized, five-arm trial testing pegozafermin at four different doses (n = 67; 52 male) versus placebo (n = 18; 12 male) for 8 weeks in patients with SHTG (triglycerides (TGs), ≥500 mg dl-1 and ≤2,000 mg dl-1). Treated patients showed a significant reduction in median TGs for the pooled pegozafermin group versus placebo (57.3% versus 11.9%, difference versus placebo -43.7%, 95% confidence interval (CI): -57.1%, -30.3%; P < 0.001), meeting the primary endpoint of the trial. Reductions in median TGs ranged from 36.4% to 63.4% across all treatment arms and were consistent regardless of background lipid-lowering therapy. Results for secondary endpoints included significant decreases in mean apolipoprotein B and non-high-density lipoprotein cholesterol concentrations (-10.5% and -18.3% for pooled doses compared to 1.1% and -0.6% for placebo (95% CI: -21.5%, -2.0%; P = 0.019 and 95% CI: -30.7%, -5.1%; P = 0.007, respectively), as well as a significant decrease in liver fat fraction for pooled treatment (n = 17) versus placebo (n = 6; -42.2% pooled pegozafermin, -8.3% placebo; 95% CI: -60.9%, -8.7%; P = 0.012), as assessed in a magnetic resonance imaging sub-study. No serious adverse events were observed to be related to the study drug. If these results are confirmed in a phase 3 trial, pegozafermin could be a promising treatment for SHTG (ClinicalTrials.gov registration: NCT0441186).
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Hipertrigliceridemia , Enfermedad del Hígado Graso no Alcohólico , Humanos , Masculino , Hipertrigliceridemia/tratamiento farmacológico , Hipertrigliceridemia/complicaciones , Factores de Crecimiento de Fibroblastos/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Triglicéridos , Método Doble Ciego , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: High-sensitivity C-reactive protein (hsCRP), a marker for atherosclerotic cardiovascular disease risk, is reduced by bempedoic acid. We assessed the relationship between changes in low-density lipoprotein cholesterol (LDL-C) and hsCRP in relation to baseline statin use. METHODS: Pooled data from four phase 3 trials (patients on maximally tolerated statins [Pool 1] and patients receiving no or low-dose statins [Pool 2]) were used to determine the proportion of patients with baseline hsCRP ≥2 mg/L who achieved hsCRP <2 mg/L at week 12. The percentage of patients who achieved hsCRP <2 mg/L and guideline-recommended LDL-C (Pool 1, <70 mg/dL; Pool 2, <100 mg/dL) was determined for patients on statins in Pool 1 and those not on statins in Pool 2, as was the correlation between percent changes in hsCRP and LDL-C. RESULTS: Overall, 38.7% in Pool 1 and 40.7% in Pool 2 with baseline hsCRP ≥2 mg/L achieved hsCRP <2 mg/L with bempedoic acid, with little effect from background statin. Among patients taking a statin in Pool 1 or not taking a statin in Pool 2, 68.6% and 62.4% achieved hsCRP <2 mg/L. Both hsCRP <2 mg/L and United States guideline-recommended LDL-C were achieved more often with bempedoic acid vs. placebo (20.8% vs. 4.3%, respectively, in Pool 1 and 32.0% vs. 5.3%, in Pool 2). Changes in hsCRP and LDL-C were only weakly correlated (Pool 1, r = 0.112; Pool 2, r = 0.173). CONCLUSIONS: Bempedoic acid significantly reduced hsCRP irrespective of background statin therapy; the effect was largely independent of LDL-C lowering.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Estados Unidos , LDL-Colesterol , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Proteína C-Reactiva/análisis , Ácidos Dicarboxílicos/uso terapéutico , Ácidos Grasos/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects ("statin-intolerant" patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo. The primary end point was a four-component composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. RESULTS: A total of 13,970 patients underwent randomization; 6992 were assigned to the bempedoic acid group and 6978 to the placebo group. The median duration of follow-up was 40.6 months. The mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid. The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = 0.004), as were the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (575 [8.2%] vs. 663 [9.5%]; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P = 0.006); fatal or nonfatal myocardial infarction (261 [3.7%] vs. 334 [4.8%]; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P = 0.002); and coronary revascularization (435 [6.2%] vs. 529 [7.6%]; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = 0.001). Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels. CONCLUSIONS: Among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization). (Funded by Esperion Therapeutics; CLEAR Outcomes ClinicalTrials.gov number, NCT02993406.).
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Enfermedades Cardiovasculares , Humanos , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/cirugía , Método Doble Ciego , Ácidos Grasos/administración & dosificación , Ácidos Grasos/efectos adversos , Ácidos Grasos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Infarto del Miocardio/epidemiología , Infarto del Miocardio/prevención & control , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Administración Oral , Revascularización Miocárdica , Hipolipemiantes/administración & dosificación , Hipolipemiantes/efectos adversos , Hipolipemiantes/uso terapéuticoRESUMEN
BACKGROUND: The rising prevalence of insulin resistance (IR), metabolic syndrome, and type 2 diabetes are associated with increases in abdominal mesenteric fat. Adipocytes are sensitive to low temperatures, making cryolipolysis of mesenteric fat an attractive treatment modality to potentially reduce IR. OBJECTIVES: We aimed to determine whether (1) cryolipolysis is safe in reducing the volume of the mesenteric fat and (2) reduction in mesenteric fat volume reduces indices of IR and glycemic dysfunction. SETTING: Indiana University School of Medicine. METHODS: A novel cooling device and method delivered cryolipolysis in a controlled manner to avoid tissue ablative temperatures. Ossabaw pigs (n = 8) were fed a high-fat diet for 9 months to develop visceral obesity, IR, and metabolic syndrome. Following laparotomy, mesenteric fat cryolipolysis (MFC) was performed in 5 pigs, while 3 served as sham surgery controls. The volume of the mesenteric fat was measured by computed tomography and compared with indices of glucose intolerance before and at 3 and 6 months postprocedure. RESULTS: MFC safely reduced mesenteric fat volume by â¼30% at 3 months, which was maintained at 6 months. Body weight did not change in either the MFC or sham surgery control groups. Measure of glycemic control, insulin sensitivity, and blood pressure significantly improved after MFC compared with sham controls. CONCLUSION: MFC reduces the volume of mesenteric fat and improves glycemic control in obese, IR Ossabaw pigs, without adverse effects.
Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Síndrome Metabólico , Porcinos , Animales , Síndrome Metabólico/cirugía , Síndrome Metabólico/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Obesidad/complicaciones , Peso CorporalRESUMEN
The ongoing obesity epidemic represents a global public health crisis that contributes to poor health outcomes, reduced quality of life, and >2.8 million deaths each year. Obesity is relapsing, progressive, and heterogeneous. It is considered a chronic disease by the World Obesity Federation (WOF) and a chronic condition by the World Heart Federation (WHF). People living with overweight/obesity are at greater risk for cardiovascular (CV) morbidity and mortality. Increased adiposity (body fat), particularly visceral/abdominal fat, is linked to CV risk and CV disease (CVD) via multiple direct and indirect pathophysiological mechanisms. The development of CVD is driven, in part, by obesity-related metabolic, endocrinologic, immunologic, structural, humoral, haemodynamic, and functional alterations. The complex multifaceted nature of these mechanisms can be challenging to understand and address in clinical practice. People living with obesity and CVD often have concurrent chronic physical or psychological disorders (multimorbidity) requiring multidisciplinary care pathways and polypharmacy. Evidence indicates that intentional weight loss (particularly when substantial) lowers CVD risk among people with overweight/obesity. Long-term weight loss and maintenance require ongoing commitment from both the individual and those responsible for their care. This position paper, developed by the WOF and the WHF, aims to improve understanding of the direct and indirect links between overweight/obesity and CVD, the key controversies in this area and evidence relating to cardiometabolic outcomes with available weight management options. Finally, an action plan for clinicians provides recommendations to help in identifying and addressing the risks of obesity-related CVD (recognizing resource and support variances between countries).