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

Objectives1. Definition, classification, and etiology of obesity2. General Approach to obesity management3. Specific Dietary Strategies4. Medications used for weight loss5. 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 Mutationso 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 concequences of lifestyle choicesTreat with medication and lifestyle changes toward specific goals

Counseling toward healthier choicesEmpowerment of patients and care providers to meet these 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 ratioo 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 overweighto >95th obese

Etiology of Obesity• Multiple contributing factors:

Genetics**Behavioral**Sleep-wake cycle**Hormones**Medications**Stress management*Microbiome

Sleep Wake cycle/ Timing of IntakeOverweight and obese women (BMI 32.4 ± 1.8

kg/m2) with metabolic syndrome were randomized into two isocaloric (∼1400 kcal)

weight loss groups, a breakfast (BF) (700 kcal breakfast, 500 kcal lunch, 200 kcal dinner) or a dinner (D) group (200 kcal breakfast, 500 kcal

lunch, 700 kcal dinner) for 12 weeks.

The two meal plans were either high-calorie breakfast (BF) or high-calorie

dinner (D) with a total daily energy of 1400 ± 25 kcal with identical macronutrient

content and composition.

Sleep Wake cycle/ Timing of Intake, cont.

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

Hormonal Factors

• Falling testosterone/ estrogen with age leads to changes in lean muscle mass and fat distribution.

• Elevated cortisol levels in OSA and chronic stress are associated with increased weight.

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

Medications inducing weight gain

• 2015 Metaanalysis in Journal of Clinical Endocrinology

As with other disease processes, important to try and stop contributing factors, as able, prior to adding new therapies

amitriptyline 2.2kgmirtazapine 1.5kgolanzapine 2.4kgquetiapine 1.1 kgrisperidone 0.8kggabapentin 2.2kgtolbutamide 2.8kgpioglitazone 2.4kgglimerpiride 2.1kgglyburide 2.6kgglipizide 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…

• Triggers and susceptibilities tend to be different for different people so identifying personal risk factors is important to put together an appropriate treatment plan

Thorough history and physical with focus on weight history and what occurred

during times of significant weight changes.

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.

• DIETFITSo 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.

Prevents weight gain in women but with no weight loss benefits.

• LOTS of benefits. Just not weight loss…

ACSM recommendations:• Weight loss 150-250 min/wk of moderate intensity aerobic• exercise.• Prevention of weight regain >250 min/wk• Resistance training 2-3 days a week

Pharmacologic InterventionEligibility: BMI >30 or >28 with co-morbidity 1. Adrenergic Agents2. Serotonergic Agents3. Lipase inhibitors4. GABA receptor antagonist5. GLP-1 receptor agonists6. Metformin7. 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 AgentsPhentermine 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 InhibitorsOrlistat (OTC and prescription strength)• Approved in 1999 for chronic weight management

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

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

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

GABA receptor antagonistsTopiramate (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, constipation, n/v

• Special Considerations: contraindicated in people with seizure disorder

GLP-1 receptor agonistsLiraglutide (Victoza or Saxenda)

Metformin• Not a medicationdesigned 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 accounto 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 ChartMedication Trade Name MOA Side effects Weight loss Expectations Who this drug may work for Doses

Phentermine

sympathomimetic amine with properties similar to the amphetamines. Stimulation of the hypothalamus to release norepinepherine

Insomnia, anxiety, palpitations and tachycardia, cardiac ischemia 3-4kg (<24 wk trials)

Appetite Suppresent. Low Cost. Higher risk factors 8,15,37.5

Liraglutide Saxenda, Victoza GLP-1 1. Glucose dependent stimulation of insulin secretion 2. reduction in plasma glucagon concentrations 3. Delayed gastric emptying 4. Direct CNS appetite suppression

Nausea and vomiting, pancreatitis, hypoglycemia 5.8kg (1 year)

Looking toward improved DMII control, difficulty with hunger and portion control 3,1.8

Lorcaserin Belviq5HT(2C) receptor agonist

HA, nausea, dry mouth, fatigue, serotonin syndrome 3.6kg (1 year)

emotional eating, appetite suppresent

Orlistat

Pancreatic and Gastric Lipase Inhibitor

steatorrhea, oily fecal spotting, fecal urgency, increased defecation 2.9-3.4kg (1 year)

limited systemic side effects (lots of GI side effects)

60, 120 BID with meals

Topirimate Topamax

GABA receptor modulation

Parathesias, fatigue, memory impairment, renal stones, teratogen

Direct appetite suppressent, binge eating tendencies, 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

MetforminDecreases hepatic glucose production, decreasing intestinal absorption of glucose and improves insulin sensitivity Dairrhea, Lactic Acidosis

Metabolic syndrome, medication induced weight gain

500mg daily -1000mg BID

Bupropion Wellbutrin

Dopamine and Norephinepherine reuptake inhibitor

Tachycardia, insomnia, HA, agitation, lowers seizure threshold binge eating tendencies 150mg BID

Over the counter supplements• No OTC supplements are FDA regulated.• In general, none are recommended

Bariatric SurgeryCandidates: 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

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