Weight Management in Primary Care

How we can partner with patients for improved success

Sarah Stolte, M.D. Assistant Professor University of Kansas Health System, Internal Medicine Objectives

1. Definition, classification, and etiology of 2. General Approach to obesity management 3. Specific Dietary Strategies 4. used for 5. Future Directions What is Obesity?

Obesity is the state of excess adipose tissue which occurs when energy intake exceeds energy expenditure

But what is obesity? Is it a result of lifestyle choices? Is it a disease process? What drives this energy imbalance? Obesity is a complex disease process

• People with overweightness and obesity don’t live as long

Yu et al. Annals of Internal Medicine, 2017; 613-621

• It is associated with impaired body function (respiratory, musculoskeletal, etc) • There are measureable physiologic abnormalities associated with the disease process • There are specific known gene mutations that lead to the condition What is known about a genetic component?

• Single Gene Mutations o Leptin Deficiency -Case Study 9yo girl

o Leptin Receptor

• Genetic Associations Recognizing Obesity as a disease process

• Lifestyle choices and disease processes are treated in very different ways.

Lifestyle (Homelessness) Disease (HTN)

Engage with support services Determine Etiology of Disease process Treat with and lifestyle changes toward specific Treat concequences of lifestyle choices goals Empowerment of patients and care providers to meet these Counseling toward healthier choices goals "Only so much we can do…" No fault assessment Prevalence and disease trajectory

https://stateofobesity.org/adult-obesity/ Indicators of Obesity

• Obesity can be measured by body composition analysis (DEXA)

• Obesity can be estimated by: o BMI o Height/ waist circumference ratio o Anthropometry (skin fold thickness) o Abdominal CT/ MRI BMI

• <18.5% - underweight • 18.6-24.9% - healthy weight • 25% - 30% - overweight >30% - obese

• For children overweight and obese is determined by percentile: o 85th-95th overweight o >95th obese Etiology of Obesity

• Multiple contributing factors: Genetics **Behavioral **Sleep-wake cycle **Hormones **Medications **Stress management *Microbiome Sleep Wake cycle/ Timing of Intake

Overweight and obese women (BMI 32.4 ± 1.8 The two meal plans were either high- kg/m2) with metabolic syndrome were randomized into two isocaloric (∼1400 kcal) calorie breakfast (BF) or high-calorie weight loss groups, a breakfast (BF) (700 kcal dinner (D) with a total daily energy of 1400 breakfast, 500 kcal lunch, 200 kcal dinner) or a ± 25 kcal with identical macronutrient dinner (D) group (200 kcal breakfast, 500 kcal content and composition. lunch, 700 kcal dinner) for 12 weeks. Sleep Wake cycle/ Timing of Intake, cont.

• Eating during light hours vs. Dark hours affects weight outcomes Hormonal Factors

• Elevated cortisol levels in OSA • Falling testosterone/ estrogen and chronic stress are with age leads to changes in associated with increased lean muscle mass and fat weight. distribution.

• Diets that aim to increase growth factor (intermittent fasting) are growing in popularity Medications inducing weight gain

amitriptyline 2.2kg mirtazapine 1.5kg • 2015 Metaanalysis in Journal of olanzapine 2.4kg Clinical Endocrinology quetiapine 1.1 kg risperidone 0.8kg gabapentin 2.2kg As with other disease processes, tolbutamide 2.8kg important to try and stop pioglitazone 2.4kg contributing factors, as able, prior glimerpiride 2.1kg to adding new therapies glyburide 2.6kg glipizide 2.2kg

sitagliptin 0.55kg Chronic Stress

• Response to acute and chronic stress is mediated differently and has different weight effects

• Regular Exercise! • Psychology • Treat underlying anxiety/ depression General Approach to obesity management

• Same as any other disease process…

Thorough history and physical with focus on weight history and what occurred during times of significant weight changes.

• Triggers and susceptibilities tend to be different for different people so identifying personal risk factors is important to put together an appropriate treatment plan Putting together a personalized weight loss strategy: • General Guidelines for people who have had success:

National weight control registry: • High levels of physical activity (>1 hour/day) • Self monitoring weight • Eating a low calorie, low fat diet • Eating breakfast regularly • Maintaining a consistent eating pattern throughout the week • Wearable activity trackers (maybe) Specific Diets

• A to Z diets • POUNDS lost • (2009) But…. • In each of these diet cohorts, the variability within each group was greater than that of the weight loss difference in between the groups.

• DIETFITS o Reanalysis of the 2007 Data for people with insulin resistance So more on personalized diets to come….

For now, focusing on what these diets have in common and having your patient choose something that is in line with their tastes and lifestyle needs is most important.

Being able to stick to dietary goals is more important the macronutrient content. Physical Activity Interventions

Exercise for weight loss Exercise for Weight Maintenance • Works modestly for men. ACSM recommendations: Prevents weight gain in women • Weight loss 150-250 min/wk of but with no weight loss benefits. moderate intensity aerobic • exercise. • LOTS of benefits. Just not weight • Prevention of weight regain >250 loss… min/wk • Resistance training 2-3 days a week Pharmacologic Intervention

Eligibility: BMI >30 or >28 with co-morbidity 1. Adrenergic Agents 2. Serotonergic Agents 3. inhibitors 4. GABA receptor antagonist 5. GLP-1 receptor agonists 6. Metformin 7. Combination Pills Pharmacologic Monitoring and Goals

• Monitor monthly x3 months at least every 3 months after that time • Effective treatment >5% weight loss at 12 weeks for any medication • If deemed ineffective, trial a different agent or consider a combination pill

• All medication are designed to be used in addition to diet and exercise. None of these medications are designed to “work on their own”

• Weight loss effects are only sustained as long as a person is taken the weight loss medication Adrenergic Agents

Phentermine and diethylpropion • Approved in 1960 for short term use

• MOA: sympathomimetic amine with pharmacologic properties similar to the amphetamines

• Side effects: elevated on MBP, increase in pulse rate, cardiac ischemia, restlessness, insomnia

• Special considerations: while this medication is only approved for short term use, it has been studied more long term in combination pills. Clinically it is generally used for longer term courses. Serotonergic Agents

Lorcaserin (Belviq) • Approved in 2012 for chronic weight management • MOA: 5HT2c receptor agonist (serotonin agonist) • Side effects: HA, nausea, dry mouth, fatigue, dizziness • Special Considerations: use with caution for people on other serotonergic agents Lipase Inhibitors

Orlistat (OTC and prescription strength) • Approved in 1999 for chronic weight management

• MOA: A reversible inhibitor of gastric and pancreatic , thus inhibiting absorption of dietary fats by 30%

• Side effects: Decreased absorption of fat-soluble vitamins, steatorrhea, oily spotting, with discharge, fecal urgency, increased defecation

• Special Considerations: this is available OTC at 60mg dose GABA receptor antagonists

Topiramate (Topamax) • Off label – used for binge eating and medication associated weight gain. FDA approved in combination drug qsymia in 2012

• MOA: Blocks neuronal voltage-dependent sodium channels, enhances GABA(A) activity, antagonizes AMPA/kainate glutamate receptors, and weakly inhibits carbonic anhydrase.

• Side effects: Parathesias, fatigue, dizziness, memory impairment

• Special Considerations: Teratogenic Dopamine/ NE reuptake inhibitor

Bupropion (Wellbutrin) • Off label for binge eating/ impulse control. FDA approved in 2014 as combo pill, contrave

• MOA: The primary mechanism of action is thought to be dopaminergic and/or noradrenergic

• Side effects: tachycardia, insomnia, dry mouth, , n/v

• Special Considerations: contraindicated in people with seizure disorder GLP-1 receptor agonists

Liraglutide (Victoza or Saxenda) Metformin

• Not a medication designed for weight loss but With metabolic outcomes Favoring weight loss Combination Pills

• Contrave – Bupropion/ Naltrexone. Increase to 180mg/16mg respectively BID. General expectation ~6% greater weight loss that diet and exercise alone.

• Qsymia – Toperimate ER/ Phentermine. Increase to 92,g/15mg daily. Titrated to weight loss goals. General Expectation ~9% greater weight loss to diet and exercise alone.

• ***- Lorcaserin/ Phentermine. This is a well researched combination though not available in combination pill yet. What Medication is the most effective?

• People tend to respond differently to different medications. When deciding on a weight loss medication take into account o Individual weight loss triggers (portion control, emotion eating, medication induced weight gain) o Co-morbidities

• Be prepared to switch! We find that there is no perfect medication – there is just a perfect medication for that individual. Set the expectation that this will be something that is achieved through follow up and flexibility.

Reference Chart

Medication Trade Name MOA Side effects Weight loss Expectations Who this drug may work for Doses sympathomimetic amine with properties similar to the amphetamines. Stimulation of the hypothalamus to release norepinepherine Phentermine Insomnia, anxiety, palpitations and tachycardia, Appetite Suppresent. Low Cost. cardiac ischemia 3-4kg (<24 wk trials) Higher risk factors 8,15,37.5

Liraglutide Saxenda, Victoza GLP-1 1. Glucose dependent stimulation of insulin secretion 2. reduction in plasma glucagon Looking toward improved DMII concentrations 3. Delayed gastric emptying 4. Direct Nausea and vomiting, control, difficulty with hunger CNS appetite suppression pancreatitis, hypoglycemia 5.8kg (1 year) and portion control 3,1.8

Lorcaserin Belviq HA, nausea, dry mouth, emotional eating, appetite 5HT(2C) receptor agonist fatigue, serotonin syndrome 3.6kg (1 year) suppresent

Orlistat steatorrhea, oily fecal spotting, fecal urgency, limited systemic side effects (lots 60, 120 BID Pancreatic and Gastric Lipase Inhibitor increased defecation 2.9-3.4kg (1 year) of GI side effects) with meals

Topirimate Topamax Parathesias, fatigue, memory Direct appetite suppressent, impairment, renal stones, binge eating tendencies, GABA receptor modulation teratogen medication induced weight gain

Naltrexone Opioid Receptor Antagonist, Naltrexone acts as an opioid receptor antagonist which is thought to indirectly modulate activation of pleasure and reward centers such as the mesolimbic dopamine system Hepatocelluar injury Food Cravings

Metformin Decreases hepatic glucose production, decreasing intestinal absorption of glucose and improves insulin Metabolic syndrome, medication 500mg daily - sensitivity Dairrhea, Lactic Acidosis induced weight gain 1000mg BID

Bupropion Wellbutrin Tachycardia, insomnia, HA, agitation, lowers seizure Dopamine and Norephinepherine reuptake inhibitor threshold binge eating tendencies 150mg BID Over the counter supplements

• No OTC supplements are FDA regulated. • In general, none are recommended Bariatric Surgery

Candidates: BMI >40, BMI >35 with co-morbidity • Roux-en-Y • Gastric Sleeve Future Directions

• Leptin • Cytokine like amino acid produced by adipocytes • Change in leptin levels signal to the CNS (hypothalamus) that fat mass is decreasing. This results in compensatory effects on appetite and energy expenditure aimed to restore the energy balance.

• Microbiome Research KU Weight Management Services

• KU Weight Management Clinic

• Bariatric Surgery Program References

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