AACE 28th Annual Scientific & Clinical Congress:

Clinical Insights on Omega-3 FAs, Weight Loss Medications, Acromegaly

with Harvey K. Chiu MD, Ann Miller, MD, and Osama Al-Taher, MD

EndocrineWeb shares the insights offered by three clinicians who attended AACE 2019, so others might benefit from sessions that inspired them to implement more targeted patient management strategies regarding hyperlipidemia, weight management, and growth hormone dysregulation.

Tackling High Triglycerides with Omega-3 Fatty Acids 

When patients present with elevated triglycerides (TGs)—estimated to affect one in four adults in the US—the recommendation for lipid-lowering therapy has been to recommend an omega-3 fatty acid (FA) supplement.1

According to the panelists participating in a satellite symposium—Embracing the new era in reducing CVD residual risk beyond statin therapy.there are a fews caveats to consider. First, some patients who receive omega-3 fatty acids (FA) to reduce hypertriglyceridemia may experience an increase in low density lipoprotein levels, which should be considered when considering the treatment plan.2

Another consideration provided to be "my ‘ah-ha’ moment—realizing that not all omega-3 fatty acids are considered of equal value,” Harvey K. Chiu MD, associate professor of pediatrics and director of the pediatric thyroid program at the David Geffen School of Medicine at the University of California, Los Angeles, told EndocrineWeb.

“We all know that omega-3 FAs are comprised of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA. While I had ben aware that there were subtle differences between the two, such as greater release of EPA from adipose tissue than DHA, these speakers well-delineated the physiologic differences between the two and concluded with the superiority of EPA regarding patient outcomes," said Dr. Chiu. 

"With this new insight, in the correct patient and at an appropriate dose, EPA has a clear advantage over DHA for the treatment of our patients. I've recognized that EPA is so much better for patients in terms of cardiovascular outcomes as supported by the American Diabetes Association recommendation of EPA for diabetic patients with elevated triglycerides to reduce their risk of cardiovascular disease,”2,3 said Dr. Chiu.

However, dietary supplements are not regulated to the same standards as prescription drugs so there is no assurance regarding the purity or potency of the long chain fatty acid contents (EPA and DHA) in an over-the-counter omega 3 FA products,2 Moreover, there are substantial differences between products with some potentially better than others.1

In particular, there are two prescription omega-3 FA formulations in the US; one that assures higher purity EPA and DHA (OM-3A ethyl esters, Lovaza) and a second that contains isosapent ethyl (IPE, Vascepa). While both formulations provided effective in lowering TGs in clinical trials, the IPE formula had the added benefit of producing no increase in LDL cholesterol.1

Since the results of cardiovascular treatment outcomes trials have been mixed,4 the American Heart Association recommends that individuals who have been diagnosed with heart disease aim for 1 gram of combined EPA/DHA daily from either dietary sources or an omega-3 FA supplement.5

The best dietary source is a serving (3.5 oz) of fatty fish (eg, salmon, halibut, lake trout, herring, and sardines.) Here, too, patients are best advised to avoid certain types of fish that contain high levels of mercury, particularly, Albacore tuna (whereas canned chunk lite tuna is low in mercury), swordfish, and King mackerel.

However, for patients on optimal statin therapy who have residual hyperlipidemia, switching them to a prescription omega-3 fatty acid to achieve the requisite reduction in cardiovascular risk.2-4

Matching the Right Weight Loss Pharmacotherapy to Each Patient

Ann Miller, MD, a first-year endocrinology fellow at the University of Maryland School of Medicine in Baltimore, told EndocrineWeb that her favorite “ah-ha” moment at AACE 2019 “occurred in the medical weight loss management session.”6

“I really liked how    [broke down the medications based on the mechanism of action so that you could tailor the particular problem that your patient has and then figure out which medication would best suit them best.”

This case-based session was presented by Ken Fujioka, MD, director of the Nutrition and Metabolic Research Center at Scripps Clinic in San Diego, California. More than 60% of patients with would consider taking medication to support weight loss if presented with the opportunity.7

Recently approved medications for weight loss:7

  • Locaserin: A serotonin 5HT-2c agonist
  • Phentermine/topiramate: Sympathomimetic combined with anti-seizure drug that increases the inhibitory effect of GABA
  • Naltrexone/bupropion: A combination of an opioid receptor agonist and a catecholamine reuptake inhibitor.
  • Liraglutide: A GLP-1 agonist
  • Gelesis100: oral super absorbent hydrogel

Factors to Consider in Selecting a Weight Loss Medication

When trying to determine which weight loss drug is the best fit for the patient, begin by considering their medical history (ie, comorbidities [diabetes, cardiovascular disease, thyroid disease], and issues like menstrual cycle, current medications) and for patients with type 2 diabetes, start with an antidiabetes medication that is known to induce weight loss.

Other issues to be considered when selecting a weight loss medication:8

  • Cost: It is reimbursed by health insurance companies or will it be out-of-pocket for the patient. For example, both GLP-1 and SGLT-2i are typically covered for patients with a diagnosis of diabetes but much less likely when prescribed for weight loss.
  • Patient preference: Oral or injectable formulation.
  • Physician familiarity and comfort with the therapeutic options.
  • Efficacy: On average, appetite increases in relation to weight lost. Ie. For every 100 calories consumed /day per kg of decrease in weight, which is more than has been previously thought. SGLT-2i alone supports only a 2-3% weight loss yet yields favorable metabolic adaptations  

Its very difficult for most individuals to maintain a weight loss of more than 20 lbs. The best option for patients with T2D is an SGLT-2i.

Consider the Multiplier Effect of Dual Therapy

There is a strong additive effect of dual therapy producing greater weight loss as demonstrated in the DURATION-8 Trial,10,11 in which combining both a GLP-1 and an SGLT2i (exenatide and depagliflozin) yielded greater weight loss and lower HbA1c levels. Whereas exenatide supported a decrease of 1.5 lbs/kg body weight, depagliflozin achieved about 2.25 kg but the combination was close to 3.5 lbs/kg body weight.10 And a greater weight loss was seen in women.

Cardiovascular Disease.  Cardiovascular Outcome Trials (CVOT): Either Liraglutide and Locerserin4,5  are recommend for individuals at high risk of cardiovascular events whereas naltrexone/bupropion and phentermine/topiramate are not recommended.

Disordered Eating:  Food Cravings, Binging For patients who present with issues of uncontrolled food cravings: Use medications that affect dopamine such as bupropion, phentermine, naltrexone. Begin with lorcaserin enhanced with phentermine.8

Always keep in mind that food is a source of pleasure, regardless of a physiological need such that many people will have dessert after finishing dinner despite feeling full, said Dr. Fujioka. Also overeating is often triggered by events, such as boredom, stress, or associated with an activity such as watching a movie, PMS. Consider combination therapy with lorcaserin and phentermine.

Overeating/binging.  Eating out of control, continuing to eat when not hungry, feeling guilty, are behavior patterns seen in 10-25% of women with type 2 diabetes (vs 2% prevalence in general population),6 he said.

Swedish investigators followed 2,342 patients diagnosed with a binge-type eating disorder for 16 years, and reported a 30% prevalence of T2D requiring mediation for glucose control.15 The investigator concluded that blood glucose metabolism may contribute to both the occurrence and perpetuation of binge eating behavior.12 

These patients responded to medications that worked on the reward/eating pathways, such as those that can increase dopamine (bupropion, stimulants), and GABA system (ie, topiramate and zonisamide to lessen food intake).13

Binge eating disorder is very common in patients with type 2 diabetes who tend to be younger.6 Approved medications for binge eating disorder: Lisdexamfetamine dimesylate (but not approved for weight loss) which has serious side effects such as insomnia, anxiety, increased blood pressure and elevated heart rate. As such, not indicated in patients with CVD. There are also off-label treatments such as GLP-1, naltrexone/bupropion, and those mentioned above.13

Enough Needs to be Enough in Treatment of Acromegaly 

Osama Al-Taher, MD, is a practicing endocrinologist at Banner Health in Sun City, Arizona. He told EndocrineWeb: “One “Ah-ha” moment occurred today while I was attending the session presented by Louis Blevins, MD, professor of neurological surgery and medicine, and director of the California Center for Pituitary disorders at the University of California at Los Angeles.

This clinical lecture on growth hormone management in patients with acromegaly focused on selecting criteria for patients who may benefit from treatment prior to surgery, for various reasons.16  It made a lot of medical sense so I actually will be putting that into practice,” Dr. Al-Taher said.

 

This rare disorder develops slowing, often presenting in adulthood with a variety of symptoms induced by a pituitary overproduction of growth hormones.16 Dr. Blevins brought along a patient he has been treating since 2010 to put a human face on this case study. Too often, symptoms are brushed off, even as physical features may seem enlarged—big hands, larger forehead or wider nose.

Unexplained weight gain and snoring are common in individuals with acromegaly but may arise from a myriad of other causes. Thus, a diagnosis is rarely made outright, leading to a delay of sometimes years,. Case in point—It took 30 years and half a dozen doctors before Dr. Blevins patient, JD, finally received an accurate diagnosis and began effective treatment.

Not only have patients experienced a lag in diagnosis of acromegaly; for far too long, treatment has been insufficient. The standard of care has been to expect that when a patient's growth hormone level fell under 5.0 ng/mL, this was considered disease-free but in many cases that cut-off was not sufficient,16 according to Dr. Blevins.

In fact, just because a patient looks “normal,” they may have still have active acromegaly. This understanding has led to a change in practice. Dr. Blevins said that in an effort to manage acromegaly, "the main advance is to pursue a management strategy that aims for a random growth hormone level of less than 1.0 ng/mL but it this isn’t achieved than it should decline to 0.4 ng/mL after oral glucose suppression and to achieve a normal IGF-1."

These patients need close follow up and a great deal of support since each patient has a distinct IGF-1 setpoint for hormone secretion,16 Dr. Blevins told EndocrineWeb. The mode of treatment is either to prescribe medication to normalize hormone production or surgery when the cause is an adenoma; sometimes radiation is recommended.

Next Summary:
Better Disease Management—Thyroid, Adrenal, Pituitary Gland Disorders
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