Major New Patient Care Trends Highlighted in the 2019 Obesity Algorithm

| July 1, 2019 | 0 Comments

by Harold Bays, MD, FOMA, FTOS, FACC, FACE, FNLA

Dr. Bays is the Medical Director and President of the Louisville Metabolic and Atherosclerosis Research Center in Louisville, Kentucky; Chief Science Officer for the Obesity Medicine Association; Board Certified in Internal Medicine and Endocrinology; and a Diplomate of the American Board of Obesity Medicine, as well as Diplomate of the American Board of Clinical Lipidology.

Funding: No funding was provided for this article.

Disclosures: Neither Dr. Harold Bays or his affiliated research center / weight management center own pharmaceutical stocks or patents. In the past 12 months, Dr. Harold Bays’ research site has received research grants from Amarin, Amgen, Alere, Allergan, Arisaph, AstraZeneca, BoehringerIngelheim, Bristol Meyers Squibb, Catabasis, Dr. Reddy, Eisai, Elcelyx, Eli Lilly, Esperion, Ferrer/Chiltern, Gemphire, Gilead, GSK, iSpecimen, Janssen, Johnson and Johnson, Kowa, Merck, Necktar, Nichi-Iko, Novartis, NovoNordisk, Pfizer, Regeneron, Sanofi, Selecta, Takeda, and TIMI. In the past 12 months, Dr. Harold Bays has served as a consultant/advisor for Alnylam, Akcea, Amgen, AstraZeneca, Eisai, Eli Lilly, Esperion, Ionis(ISIS), Janssen, Johnson & Johnson, Kowa, Merck, Novartis, Prosciento, Regeneron, and Sanofi. In the past 12 months, Dr. Harold Bays has served as a speaker for Amarin, Amgen, Eisai, Kowa, Orexigen, Regeneron, and Sanofi.

Bariatric Times. 2019;16(7):8–11.

Obesity has grown to epidemic proportions in the first quarter of the 21st century. More than 70 percent of the United States adult population have either overweight or obesity. Obesity is the leading cause and/or contributing factor to the most common metabolic diseases encountered in clinical practice (e.g., diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease, fatty liver), as well as many types of cancer.

The Obesity Medicine Association (OMA) defines obesity as a chronic, progressive, relapsing, multifactorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.

Both clinicians and the general public benefit from an improved understanding that obesity is a complex, multifactorial disease. The cause of obesity goes beyond lifestyle choices, and includes the following:

  • Genetic or developmental errors
  • Infections
  • Hypothalamic injury
  • Adverse reactions to medications
  • Nutritional imbalance
  • Unfavorable environmental factors

In response to the need for greater understanding of the disease, starting in 2013, the OMA developed the Obesity Algorithm® to assist healthcare professionals in providing care for patients with overweight and obesity. This comprehensive educational document is not intended to dictate “rules” regarding the medical care of individual patients.  Rather, it is to reflect the latest in peer-reviewed trends in diagnostics, treatment, and research – presented in a way that is both practical and applicable to patient care.

Since its beginning, the Obesity Algorithm has undergone yearly updates.  A number of major updates in the science and treatment of obesity are presented in the 2019 edition, including new sections on the following:

  • Obesity and cardiovascular disease
  • Obesity and diabetes mellitus
  • Obesity and dyslipidemia
  • Obesity and fatty liver
  • Obesity and cancer
  • Expansion of investigational anti-obesity pharmacotherapy
  • Pharmacokinetics and obesity

Obesity and Cardiovascular Disease

Cardiovascular disease (CVD) is the most common cause of mortality among patients with obesity. Therefore, patients with obesity should undergo global CVD risk assessment and risk reduction. Interventions include healthy nutrition and appropriate physical activity, stopping smoking, as well as optimal control of blood sugars, blood pressure, and lipids.

While CVD outcomes trials are ongoing with anti-obesity agents, no drug and dose having an indication to treat obesity has proven to improve CVD outcomes. Lorcaserin is illustrative of an anti-obesity agent that does not increase the risk of CVD among patients with obesity, and which may reduce the onset of diabetes mellitus by mechanisms independent of weight loss. Similarly, retrospective data suggest that phentermine and topiramate may not increase the risk of major adverse cardiac events.

Meanwhile, when evaluated to treat diabetes mellitus, some glucagon-like peptide 1 (GLP-1) agonists do have clinical outcome trial evidence to support CVD benefits (e.g., liraglutide, semaglutide). These same agents are currently being evaluated in CVD outcomes trials in patients with obesity. Similarly, in patients with type 2 diabetes mellitus, metformin, and sodium-glucose co-transporter-2 (SGLT2) inhibitors may decrease CVD. While these agents do not have an indication as anti-obesity agents, they may modestly reduce body weight in patients with and without diabetes mellitus.

Finally, most other anti-obesity agents do not have CVD outcome data to support CVD event reduction when specifically evaluated in patients with obesity. Having said this, many anti-obesity drugs reduce CVD risk factors (e.g., orlistat, lorcaserin, naltrexone/bupropion, and phentermine/topiramate) and are not contraindicated in patients with cardiovascular disease.

Obesity and Diabetes Mellitus

The disease of obesity is an important contributor to the disease of type 2 diabetes mellitus, most likely due to adiposopathic immunopathies, endocrinopathies, and adiposopathic lipotoxicity.

Unfortunately, sulfonylureas and many insulins used to treat diabetes mellitus often increase body weight, and in some cases, increase the risk for CVD. Treatment protocols for patients with obesity and diabetes, therefore, include the same global CVD risk reduction measures mentioned above, including focusing on healthy nutrition and physical activity and stopping smoking, as well as optimal control of blood sugar, blood pressure, and lipids.

Based on cardiovascular outcome trial data of patients with type 2 diabetes mellitus (consisting mostly of patients with CVD), SGLT2 inhibitors (e.g., empagliflozin and canagliflozin) may reduce major adverse cardiac events, reduce heart failure, reduce cardiovascular death or heart failure hospitalization, reduce renal disease progression, and in some cases, reduce overall mortality. Body weight and blood pressure may be modestly decreased as well. The benefits of SGLT2 inhibitors seem to be similar among patients with body mass index (BMI) more than 30kg/m2 versus BMI less than 30kg/m2.

Other drugs being studied include liraglutide at the 1.8mg dose to treat diabetes, which may reduce CVD among patients with diabetes mellitus, and reduce body weight and blood pressure. Metformin decreases CVD among patients with diabetes mellitus, and modestly reduces body weight in patients with diabetes mellitus. Finally, both liraglutide and lorcaserin may lower blood sugar through weight dependent and weight independent mechanisms.

Obesity and Dyslipidemia

Dyslipidemia is an important risk factor for CVD.  Obesity is an important contributor to dyslipidemia. As with other common metabolic diseases, among the most common causes of dyslipidemia include adiposopathic inflammation, endocrinopathies, and lipotoxicity.

Once again, patients with obesity and dyslipidemia should undergo global CVD risk reduction measure (healthy nutrition and physical activity, stopping smoking, and optimal control of blood sugar, blood pressure, and lipids). Many anti-obesity agents improve dyslipidemia.

Obesity and Cancer

Obesity is the second most common preventable cause of cancer and may soon overtake smoking as the most common preventable cause of cancer. Obesity and adiposopathy (“sick fat disease”) increase the risk of many cancers, includingthe following:

  • Bladder cancer
  • Brain cancer
  • Breast cancer (postmenopausal)
  • Cervical cancer
  • Colon cancer
  • Endometrial/uterine cancer
  • Esophageal cancer
  • Gallbladder cancer
  • Head and neck cancer
  • Kidney/renal cancer
  • Leukemia
  • Liver cancer
  • Multiple myeloma
  • Non-Hodgkin lymphoma
  • Ovarian cancer
  • Pancreatic cancer
  • Prostate cancer*
  • Stomach cancer
  • Thyroid cancer

* Not necessarily increased risk but prognosis is worse

Obesity is believed to cause cancer through adiposopathic immunopathies, endocrinopathies, and hypoxia.

Among United States adults, the proportion of cancers attributable to excess body weight is about five percent for men, and about 10 percent for women. An increase in body weight may also be contributing to an increase in cancer among young adults.

No drug has an indication to treat obesity and prevent or treat cancer. However, evidence supports that among patient with obesity, weight reduction via appropriate nutrition and physical activity may help prevent cancer, enhance chemotherapy for cancer, and reduce recurrent cancer. Weight reduction in patients with overweight or obesity may reduce inflammation; reduce cancer cell multiplication; enhance cancer cell death; enhance response to cancer treatment and reduce the risk for future cancer. Bariatric surgery may also reduce risk of hormone-related cancers.

In addition to weight reduction, a nutritional priority is to avoid cancer-promoting foods and other carcinogenic exposures, accompanied by an intake of healthy foods, such as those containing antioxidants (e.g., vitamin C, lycopene, and beta-carotene).

Expansion of Investigational Anti-obesity Pharmacotherapy

Novel anti-obesity agents not only focus on reducing the weight of patients, but also seek to improve the health of patients via an improvement in metabolic diseases, CVD, and cancer.

Among the more promising anti-obesity drugs include glucagon-like peptide-1 agonists, oxyntomodulin [dual GLP-1/glucagon (GCG) receptor agonists], and glucagon-like peptide-1 (GLP-1) combined with:

  • Unimolecular dual GLP-1 / GCG coagonist
  • Multifactorial peptide dual GLP-1 / gastric-inhibitory peptide (GIP) coagonist (“twincretin”)
  • GLP-1 / GIP / GCG tri-agonist
  • GLP-1 / peptide YY

Despite clinical trials supporting the safety and efficacy of some phentermine-based combination therapies, the prescribing information for phentermine includes a precaution that, due to the lack of established safety and efficacy, the combination of phentermine with other drugs for weight loss is not recommended.

Pharmacokinetics and Obesity

Pharmacokinetics refers to the branch of pharmacology concerned with drug absorption, metabolism, distribution and excretion, all which may be affected by obesity. 

With regard to absorption, systemic availability depends on whether intravenous, subcutaneous (SQ), and intramuscular administration is used to administer the drug. Individuals with obesity may present challenging intravenous access. Intramuscular administration may require longer needles for patients with obesity. Obesity may decrease SQ absorption due to reduced subcutaneous blood flow per unit volume of SQ tissue. Requirements for higher volumes of subcutaneous drug (e.g., insulin) may decrease absorption per unit of drug.

Lipophilic drugs may have a larger volume of distribution (diffused in body fat and other body tissues), while hydrophilic drugs tend to reside in the blood. While the knowledge of lipophilicity and hydrophilicity may help guide dosing, a challenge is that, often, no systematic relationship exists between the degree of lipophilicity of markedly lipophilic drugs and their distribution in individuals with obesity. Practically, this means dosing of drugs is best determined via data derived from studies carried out in individuals with obesity.

Complications of obesity may affect excretion from renal insufficiency due to diabetes mellitus or hypertension. Measurement of glomerular filtration rate (GFR) represents the blood filter by the kidney, often assessed by fructose-based polysaccharide (i.e., inulin) that is neither secreted or reabsorbed across tubules. However, estimates of GFR are often not validated for obesity.

A Patient-centered Approach to Obesity

The 2019 Obesity Algorithm provides an overview of the principles critical to the care of patients with increased and/or dysfunctional body fat (adiposopathy). The content of the OMA Obesity Algorithm is based on relevant scientific evidence, supported by medical literature, and derived from the clinical experiences of members of the OMA.

Going forward, it is hoped that more effective and better tolerated anti-obesity agents will continue to be developed. It is hoped that obesity will continue to be better recognized as a disease. It is hoped that bias regarding the treatment of patients with obesity will continue to dissipate, allowing patients more and better options that will not only improve the weight of patients with obesity, but also improve their health as well.

While it should not be considered a directive of care, the OMA Obesity Algorithm does provide the clinician with evidenced-based approaches to the patient with obesity. It also incorporates the experiences of Obesity Medicine specialists. Because when evidence is lacking, “expert opinion” may be useful to help provide generalized treatment options. Most of all, the OMA Obesity Algorithm embraces the concept that obesity should always be treated via a patient-centered approach that is unique for each patient, with individualized treatment options that are in the best interest of the individual patient. 

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Category: Medical Methods in Obesity Treatment, Past Articles

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