OBESITY

Obesity
• Obesity is a condition associated with excess body weight, specifically with the
deposition of excessive adipose tissue. Obesity is considered a global epidemic.

• Major influences come from the western diet and sedentary lifestyles, but the exact
mechanisms likely include a mixture of genetic and environmental factors. Several
conditions are associated with obesity, including diabetes, hypertension, and heart
disease, all of which contribute to significant healthcare costs.
 Diagnosis

• Diagnosis is most commonly based on BMI measurement, wherein obesity is

defined as BMI > 30. Management includes lifestyle changes, medications, or, in
severe cases, bariatric surgery.
Obesity Measurements

➢ Obesity can be precisely defined by BMI or

body fat percentage.

➢ Waist circumference is a measure of

abdominal obesity and is associated with
increased cardiovascular risks.

BMI is calculated as weight (kg)/height² (m²).

BMI classification:
• Underweight < 18.5
• Normal weight: 18.5–24.9
• Overweight: 25–29.9
• Obesity: 30–39.9
• Morbid obesity: > 40
Obesity Measurements

• Body fat percentage = 1.2(BMI) + 0.23(age) - 10.8(sex) - 5.4:

– Normal:
• Men (sex= 1): 15%–20%

• Women (sex = 0): 25%–30%

– Obesity:
• Men: > 25%

• Women: > 33%

• Waist circumference indicating increased cardiac risk:

– Men: > 102 cm (40 in)
– Women: > 88 cm (34.5 in)
Epidemiology

• ⅓ or more adults in the United States suffer from obesity.

• Prevalence appears to be steadily increasing and shows a slightly

increased prevalence in women compared to men.

• There was an increase in the prevalence of obesity from 19.4% in 1997 to 31.4% in
2017.

• About 17% of children and adolescents are affected.

• In 2015, approximately 108 million children and 604 million adults globally were
obese.
 Etiology
• The nature of obesity is believed to be multifactorial. Sedentary lifestyle and increased
caloric intake appear to be the most common causes.
✓ Dietary factors: Overeating, high-fat diets
✓ Social/behavioral factors: Socioeconomic factors, psychological factors, night eating,
binge eating
✓ Sedentary lifestyle: Poor exercise habits, sedentary jobs, inactivity due to surgery,
disability, aging
✓ Iatrogenic: due to certain medications, hypothalamic surgery
✓ Genetic conditions
✓ Underlying neuroendocrine disorders: Cushing's syndrome, hypothyroidism, growth
hormone deficiency, hypogonadism
Secondary Causes of Obesity

❖ Hypothyroidism: a condition caused by the deficiency of T3 and T4. Clinical features of hypothyroidism
reflect the effects of decreased metabolic rate and include fatigue, bradycardia, cold intolerance, and weight
gain. Diagnosis is based on thyroid function tests. Elevated thyroid stimulating hormone and low free
thyroxine (T4) are noted. Treatment is with synthetic T4.
❖ Cushing's syndrome: a disorder that occurs due to hypercortisolism. Cushing's syndrome may result from
the excessive use of corticosteroids or something in the body that produces excess cortisol. Clinical features
include central obesity, round moon face, hump of fatty tissue on the upper back/neck, abdominal striae,
and easy bruising. Cushing's syndrome is associated with hypertension and hyperglycemia. Diagnosis is
based on the measurement of cortisol levels. Treatment depends on the cause of the excess level of cortisol.
❖ Prader-Willi syndrome: a rare genetic neurodevelopmental disorder. Prader-Willi syndrome is associated with
hypotonia, short stature, intellectual disability, and obesity. Extremely high ghrelin levels in patients are
hypothesized to be culpable for obesity, hyperphagia, and voracious appetite. Genetic testing confirms the
diagnosis. A multidisciplinary treatment approach includes weight management, a range of therapies (i.e.,
physical, language, behavioral), and condition-specific treatments.
 Disorders Related to Obesity

❖ PCOS: a common endocrine disorder affecting reproductive-aged women. Polycystic ovarian syndrome is characterized by
hyperandrogenism, irregular menstrual cycles, and metabolic dysfunction, and is known to increase the risk of infertility and
cardiovascular disease. Etiology is uncertain but genetics and excess hormone levels are believed to play a role. Diagnosis is
based on exclusion. Management includes attempting to restore normal ovulation through weight loss, oral contraceptive pills,
and assistance with fertility.

❖ Metabolic syndrome: a group of health problems that includes hypertension, impaired fasting glucose levels, dyslipidemia, and
a large waist circumference. Patients are characteristically overweight with predominant central (abdominal)-fat distribution.
Diagnosis is made based on the presence of the above conditions after exam and blood tests. Management involves lifestyle
changes and medications to manage associated health problems.

❖ Diabetes mellitus type 2: a metabolic disorder characterized by chronic hyperglycemia with elevated urine sugar. Type 2
diabetes mellitus results from insulin resistance in tissues and/or the inability of the pancreas to synthesize adequate insulin.
Symptoms include increased thirst, frequent urination, increased hunger, fatigue, and paresthesias. Blood tests are used to
confirm the diagnosis. Management involves lifestyle changes and medications.
 Disorders Related to Obesity

❖ Obstructive sleep apnea: a condition characterized by episodic apnea or cessation of breathing during sleep, wherein the
period of apnea lasts > 10 seconds. Obstructive sleep apnea results from a partial or complete collapse of the upper airway
and is associated with snoring, restlessness, daytime headache, and somnolence. A sleep study is used to confirm the
diagnosis. Management involves weight loss and the use of devices, such as a continuous positive airway pressure (CPAP)
machine, which helps keep the airway open.

❖ Meralgia paresthetica: a condition caused by compression of the lateral femoral cutaneous nerve, which supplies sensation to
the upper lateral thigh. Meralgia paresthetica is marked by tingling, numbness, and burning pain in the outer part of the upper
lateral thigh and is common in individuals with high BMI. Diagnosis is based on history and exam, although tests may be
conducted to rule out other conditions. Management involves weight loss, drug therapy, steroid injections, and in rare cases,
surgical decompression.
Medications Associated with Weight
Gain

Steroids: Diabetes medications: Antipsychotics: Antidepressants:

•Prednisone •Insulin •Risperidone •Paroxetine

•Sulfonylureas •Quetiapine •Citalopram
•Thiazolidinediones •Olanzapine •Amitriptyline
•Mirtazapine

Mood
Hormonal agents Beta-blockers Alpha-blockers stabilizers/neurological
agents:
•Progestins : •Propranolol •Terazosin •Carbamazepine
medroxyprogesterone •Valproate
•Lithium
•Gabapentin
➢ Obesity may be hypertrophic (increased size of adipocytes) or hypercellular (increased
number of cells):
– The hypertrophic variant is typical of android (abdominal) obesity.
– The hypercellular variant is frequently associated with childhood and very severe obesity.
Hormones
• A number of hormones are involved in the regulation of appetite, satiety, metabolism, and fat
distribution.
• Orexigenic hormones involved in appetite stimulation include:
• Ghrelin
• Endocannabinoid
• Neuropeptide Y

• Anorexigenic hormones involved in appetite suppression include:

• Leptin
• GLP-1
• Peptide YY
Ghrelin and Leptin
• 2 hormones that likely play the biggest role in regulation of appetite and body weight
are ghrelin and leptin
➢ Ghrelin
• Mainly produced in the stomach
• Sends signals to the lateral nucleus of the hypothalamus (hunger center) to ↑ appetite and stimulate hunger
• Levels ↑ during starvation/fasting and sleep deprivation
• Levels ↓ after food intake
➢ Leptin
• Primarily produced by adipose tissue
• Sends signals to the ventromedial nucleus of the hypothalamus(satiety center) to decrease appetite
• Opposes ghrelin by signaling the sense of satiety to the hypothalamus
• Levels ↑ with food intake and with ↑ in weight and body fat due to increasing leptin resistance
• Levels ↓ with starvation, sleep deprivation, and exercise
Obesity-associated Morbidity

• Obesity is associated with increased mortality and negatively impacts almost every organ system. Abdominal obesity is
specifically associated with increased cardiovascular risks.

• Cardiovascular:
– Coronary artery syndrome
– Hypertension
– Cardiomyopathy
– Ventricular hypertrophy
– Heart failure
– Varicose veins
– Deep vein thrombosis
Obesity-associated Morbidity
• Respiratory:
– Obstructive sleep apnea
– Asthma
– Respiratory infections
– Obesity hypoventilation syndrome

• Neurological:
– Increased risk of hemorrhagic and ischemic stroke in men
– Meralgia paresthetica (compression of the lateral cutaneous nerve of the thigh)

• Genitourinary/reproductive:
– Polycystic ovarian syndrome
– (PCOS)
– Macrosomic babies and subsequent pelvic dystocia
– Stress incontinence
Obesity-associated Morbidity
• Skin
– Increased risk of infection and cellulitis due to poor circulation
– Acanthosis nigricans secondary to metabolic changes

• Endocrine/metabolic:
– Type 2 diabetes mellitus
– Metabolic syndrome
– Dyslipidemia
– Hypercholesterolemia

• GI:
– Gallbladder disease
– GERD
Obesity-associated Morbidity
• Musculoskeletal: knee osteoarthritis

• Hematology/oncology:
– Lymphadenopathy
– ↑ Risk for lung, pancreatic, renal, and gastric cancers in both genders
– ↑ Risk for endometrial, ovarian, and breast cancers in women
– ↑ Risk for prostate, colon, and rectal cancer in men
Diagnosis

• Identify factors contributing to obesity:

– Lifestyle (occupation, exercise)
– Diet/caloric intake
– Duration of a problem/age of onset
– Previous weight-loss attempts
– Smoking cessation (may stimulate increased caloric intake)
– Family history

• Rule out secondary causes:

– Medications (e.g., steroids, antipsychotics)
– Diseases:
• Hypothyroidism
• Cushing's syndrome
Physical exam

• Individuals should be screened to obtain BMI measurements.

• There are some caveats in using BMI:

– BMI does not account for the percentage of weight that is muscle versus fat, and may overestimate
adiposity in muscular individuals (i.e., athletes, bodybuilders).
– BMI may underestimate adiposity in individuals, such as the elderly, who may have lost muscle mass
– secondary to aging.
– BMI does not take into account the distribution of body fat, such as abdominal obesity, which is a
risk factor in itself.

• Body-fat percentage may be a more accurate tool to evaluate muscular individuals.

• Waist circumference should be measured in individuals having BMI ranging from 25–35 to
assess abdominal adiposity.
Laboratory

• Fasting glucose and/or HbA1c

• Thyroid-stimulating hormone (TSH)

• Liver enzymes

• Fasting lipids

• Cholesterol

• Further tests should be performed if history, exam findings, or initial labs raise
suspicion of secondary causes:
– Growth hormone levels
– Adrenocorticotropic hormone/cortisol
Management

Goals of treatment

• To prevent, treat, or reverse obesity-related morbidity

• Weight loss of 5%–7% of body weight is associated with reducing the risk
of diabetes, hypertension, and dyslipidemia.

• In individuals with BMI > 30, weight loss of approximately 25 lbs is associated with a
reduced risk of cardiovascular disease, cancer, and overall mortality.
 Lifestyle/Behavior Modifications

➢ 1st step in the management of obesity

➢ Dietary changes:

• Decreasing caloric intake relative to caloric expenditure

• Recommended caloric intake for weight loss: 800–1200 kcal/day

• Specific type of diet not as important, but overall healthier food choices should be recommended

➢ Increase physical activity/exercise

➢ Behavior therapy/modification:

• Recommended to help patients make long-term changes

• Encourage patients to modify and monitor food intake and physical activity and increase awareness of
triggers that stimulate eating.
• Create short-term realistic goals to change patient behaviors and develop a plan for accomplishing goals.

➢ Patient education:

• Educate the patient about the risks and benefits associated with their weight and lifestyle habits.

• Counsel patients on healthier nutrition habits and choices of physical activity.

Medications

• Weight-loss medications are reserved for patients who have:

✓ Failed to lose > 5% total body weight within 3–6 months after modifications in lifestyle
behavior alone, AND have
✓ BMI of ≥ 27 with comorbidities
✓ BMI of 30 with or without comorbidities
Medications
• Use of medications for weight loss typically results in a weight loss of 4%–8% of body
weight over a period of 6–12 months.
• Combining lifestyle/behavioral changes with weight-loss medications results in
greater weight loss than with medications alone.
• Choice of the anti-obesity agent is based on the comorbidities and
relative contraindications relevant to the patient.
• Weight loss, blood pressure, and heart rate of the patient should be closely monitored
for the duration of medical management.
• Discontinuation of weight-loss medications has been associated with regaining weight.
 D u r a t i o n o f Tr e a t m e n t
• If the patient does not lose 4%–5% baseline body weight by 12
weeks at the maximum tolerated dose, the medication should be
tapered and discontinued.
• Continuation of weight-loss medications for long-term use may be
considered if:
– Medication has been well-tolerated
– At least 5% of weight reduction from baseline has occurred and
lasted 6 months after starting medication
 Medications approved for short-term use Medications are approved for long-term
(< 12 weeks): use in weight-loss management

• Controlled substances with amphetamine- • Glucagon-like peptide-1 (GLP-1) agonists:

like effects and potential for abuse: semaglutide or liraglutide
✓Phentermine •Orlistat
✓Benzphetamine •Phentermine-topiramate
✓Diethylpropion •Naltrexone-bupropion
✓Phendimetrazine •Setmelanotide approved for genetic causes
of obesity, including:
✓Proopiomelanocortin (POMC) deficiency
✓Proprotein convertase subtilisin/kexin type
1
✓(PCSK1) deficiency
✓Leptin receptor (LEPR) deficiency
 Medications
• Medications may also be needed to manage comorbidities such as hypertension, diabetes,
hyperlipidemia, and depression:

• If possible, avoid medications associated with weight gain.

• Select medications that may also result in weight loss

• Examples of medications that may aid weight loss

– Metformin or semaglutide (Ozempic) used in the management of diabetes
– Fluoxetine (Prozac) used in the management of psychiatric disorders
Phentermine
• Works by reducing appetite ( anorexiant, CNS stimulant)

• Phentermine is similar to an amphetamine and stimulates the central nervous system, which can
increase heart rate and blood pressure and decrease appetite.

• It is approved for use for up to 12 weeks.

• Phentermine may also be habit-forming and can cause addiction, overdose, or death if misused

• May develop tolerance

• Not recommended for use in pediatric patients ≤16 years.

• The usual adult dose is one tablet (37.5 mg) Daily. The recommended maximum dosage of
Phentermine is 15 mg daily for patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73m2)
Phentermine
Contraindicated in
– Pregnancy, breast-feeding (category X)
– History of cardiovascular disease
– During or within 14 days following the administration of monoamine oxidase
inhibitors
– Hyperthyroidism
– Glaucoma
– History of drug abuse
Phentermine Drug Interactions
Monoamine Oxidase Inhibitors
– Use of Phentermine is contraindicated during or within 14 days following the administration of
monoamine oxidase inhibitors because of the risk of hypertensive crisis.

Alcohol
– Concomitant use of alcohol with Phentermine may result in an adverse drug reaction.

Insulin and Oral Hypoglycemic Medications

Adrenergic Neuron Blocking Drugs

– Phentermine may decrease the hypotensive effect of adrenergic neuron blocking drugs.
Adverse Reactions/ Side Effects
• Cardiovascular; Primary pulmonary hypertension and/or regurgitant cardiac valvular
disease, palpitation, tachycardia, elevation of blood pressure, ischemic events.
• Central Nervous System; Overstimulation, restlessness, dizziness, insomnia, euphoria,
dysphoria, tremor, headache, psychosis.
• Gastrointestinal; Dryness of the mouth, unpleasant taste, diarrhea, constipation, other
gastrointestinal disturbances.
• Impotence, change in libido

• Effect on the ability to engage in potentially hazardous tasks

• Withdrawal effects following prolonged high dosage administration

• Allergic reactions
Benzphetamine
• Benzphetamine is a stimulant similar to amphetamine ; appetite suppressant.

• Slightly increases metabolism

• 20-50 mg orally once a day initially, 20 to 50 mg one to three times a day as

maintenance dose.

• BMI of 30 kg/m2 or higher

• Patients younger than 12 years old can not use.

• Short- term treatment, stop if no weight loss after 4 weeks.

• Pregnancy category X.
Contraindications
• Coronary artery disease

• Heart disease

• High blood pressure

• Hyperthyroid

• Glaucoma

• Pregnancy

• History of drug/ alcohol abuse

• MAO inhibitor in the past 14 days

Adverse Reactions/ Side Effects
• Allergic reactions

• Shortness of breath, swelling, rapid weight gain

• Chest pain

• Pounding heartbeat, chest fluttering

• Confusion, irritability, unusual thoughts

• Dangerously high blood pressure ( headache, shorthness of breath, confusion, chest pain,
blurred vision)
• Restlessness, hyperactive, headache, dizziness, tremors, insomnia, sweating, dry
mouth,nausea, diarrhea, upset stomach, skin rash
Diethylpropion

• Similar to amphetamine, stimulant, appetite suppressant.

• Short-term use, stop if no weight loss after 4 weeks

• 25 mg 3 times a day, 75 mg once a day ( controlled release)

• > 16 years old. BMI> 30

• Similar to other stimulants, containdicated in pumonary hypertension, coronary artery

disease, high blood pressure, overactive thyroid, history of drug abuse, glaucoma,,
agitated states
• Pregnancy category B, ( baby might become dependent and have withdrawal
symptoms when born).
Phendimetrazine

• Similar to amphetamine, appetite suppressant.

• Similar contraindications and adverse effects/ side effects

• Addiction, overdose, death

• Extented release; 105 mg once a day or 35 mg 2 or 3 times a day.

• Pregnancy category C ( not recommended in pregnancy)

Orlistat
• Orlistat reversibly inhibits gastric and pancreatic lipases. The inactivation of lipases
prevents hydrolysis of triglycerides, and fatt acids are not absorbed.

• Reduction in BMI, waist circumference, total cholesterol and LDL levels.

• Reduction in the incidence of diabetes in patients with impaired glucose tolerance.

• 60- 120 mg capsules available

• 120 mg 3 times a day, during or within 1 hour after fat-containing meal.

• Diet should be less than 30% calories from fat.

• Monitor BMI, waist and lipid profile during treatment.

Orlistat
• If patient misses a meal, skip orlistat dose.

• If patients forgets to take a pill, and it is more than 2 hours, no need to take it as most
of the fast absorption already occurred around that time.

• Orlistat also reduces the absorption of fat-soluble vitamins, patients should take
multivitamin supplements ( fat-soluble vitamins) daily.

• Multivitamin- orlistat – give more than 2 hours gap.

• Patient should lose 5% of starting body weight in 3 months.

Orlistat
• Not used in pediatrics. Safe in adolescents

• Safe in renal impairment

• Pregnancy category is X.

• Can be used when breastfeeding but mothers should take multivitamin. ( although diet
is not recommended when breastfeeding)

• Patients with diabetes might need to adjust diabetes medication dose, weight loss can
affect glycemic control.
Adverse Effects/ Side Effects
• Most common side effects are gastrointestinal.( steatorrhea, fecal spotting, diarrhea,
abdominal pain, anal fissures)
• Steatorrhea- impaired absorption of dietary fat.

• Cholelithiasis, pancreatitis acute cholestatic hepatitis- rarely

• Hepatotoxicity ( hypersensitivity related, only a small amount can cause)

• Risk of acute kidney injury (unabsorbed fat binds with calcium in the intestinal lumen
resulting in excessive oxalate, which is absorbed and deposited in the kidney leading to
oxalate nephropathy and increased risk of renal stones)
• Osteoporosis

• Increase risk colorectal cancer in animal studies.

Drug Interactions
• Antiepileptics; reduce the absorption of lipophilic antiepileptics

• Amiodarone; reduce the absorption

• Cyclosporine; reduce the absorption

• Levothyroxine; reduce the absorption ( take 4 hours apart)

• Warfarin; prolonged prothrombin time and INR ( orlistat reduces the absorption of vit K)

• Antiretrovirals; reduce absorption. Monitor viral load.

Contraindications
• Chronic malabsorption

• Cholestasis

• Anorexia and bulimia

• Pregnancy

• Severe renal impairment

• Hypersensitivity
Naltrexone-Bupropion

• Naltrexone- a opioid antagonist

• Bupropion- an aminoketone antidepressant

• Mechanism not fully understood. Promotes satiety, reduce food intake, enhance
energy expenditure. The reduction in food intake is larger than reduction seen with
either agent alone.

• After 12 weeks of treatment with naltrexone/bupropion, a patient should have

achieved at least a 5% weight loss since initiation of therapy. If this result is not attained
within 12 weeks, then naltrexone/bupropion should be discontinued because it is
unlikely that the patient will derive benefit from it.
Naltrexone-Bupropion

• 8 mg Naltrexone- 90 mg Bupropion

• Week 1- One tablet in the morning for one week

• Week 2- add another tablet in the evening

• Week 4- 2 tablets twice a day – ( 32 mg Naltrexone, 360 mg Bupropion)

• Min 8% weight reduction in 56 weeks.

May cause nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth,
diarrhea

-suicidality, neuropsychiatric reactions

Naltrexone-Bupropion
• Not recommended < 18.

• > 65 years old may be more sensitive to CNS adverse effects

• Patients using opioids may not benefit as naltrexone is a opioid antagonist

• Bupropion not to be used with monoamine oxidase inhibitor ( hypertensive reactions)

• Bupropion has a dose-related propensity to cause seizures.

• Caution when also using anti-psychotics, antidepressants, theophylline or systemic

corticosteroids because of an enhanced risk of seizure
• Use with levodopa or amantadine- restlessnes, agitation,tremor, ataxia,vertigo,dizziness
( due to combined dopamine agonistic effects)
P h e n t e r m i n e -To p i r a m a t e

• Phentermine alone has been used for short-term treatment for obesity.( anorectic)

• Topiramate has been used to treat partial onset or primary generalized tonic-clonic
seizures and migraine headaches. ( appetite suppression, satiety enhancement)
• Combination is used to treat obesity.

• 3.75 mg/23 mg, 7.5 mg/46 mg, 11.25 mg/69 mg, and 15 mg/92 mg of phentermine
mg/topiramate mg ER.
• It is recommended to take this medication in the morning to prevent insomnia.
• Start with the lowest dose 3.75/ 23 mg for 14 days, increase to 7.5/46 mg. Reevaluate
in 12 weeks.
P h e n t e r m i n e -To p i r a m a t e
• If 3% weight loss is not achieved after 12 weeks on the 7.5 mg/46 mg phentermine
mg/topiramate mg ER dosage, discontinue or escalate the dose to 11.25 mg/69 mg
every morning for 14 days. Reevaluate again in 12 weeks.

• If 5% weight loss is not achieved after 12 weeks on the maximum dose of 15 mg/92
mg phentermine mg/topiramate mg ER, discontinue by gradually tapering the dose to
prevent possible seizures.

• Based on clinical trial data, about 70% of patients lose 5-10% of their body weight over
56 weeks.
P h e n t e r m i n e -To p i r a m a t e
• Renal Impairment: For patients with severe renal impairment, it is recommended that
the clinician should not prescribe more than 7.5 mg/46 mg phentermine
mg/topiramate mg ER per day. ( also for hepatic impairment)

• Pregnancy category X ( oral clefts in the first trimester, metabolic acidosis, growth
restriction, hypoxic events).

• Not to be used when breastfeeding, hypertension and weight loss

Adverse effects/ Side effects
• Dry mouth, constipation, paresthesia.

• Topiramate ; hypohidrosis, hyperthermia ( avoid anticholingergics)

• Increase resting heart rate upto 20 bpm. ( monitor heart rate)

• Phentermine associated with valvular heart disease.

• Psychiatric and cognitive disturbances. Mood disorders, anxiety, depression, insomnia

• Suicide ideations, depressed mood, anxiety

• Increased risk of hypokalemia, hypoglycemia, CNS depression

• Abrupt withdrawal may trigger seizures

Contraindications
• Pregnancy

• Glaucoma

• Hyperthyroidism

• Use of MAOI – hypertensive crisis

• Use of inhaled anesthetics

• Use of SSRI can cause serotonin syndrome- high temperature, agitation, sweating,
tremors, dilated pupils, hyperreflexia, diarrhea, seizures, irregular heartbeat,
unconsciousness.
G l u c a g o n - l i k e Pe p t i d e - 1 ( G L P- 1 )
Agonists
• Also known as GLP-1 receptor agonists, incretin mimetics, or GLP-1 analogs

• Treatment of type-2 diabetes and obesity

– Exenatide, Lixisenatide, Liraglutide, Albiglutide,dulaglutide And Semaglutide.

• Semaglutide and high-dose Liraglutide are FDA approved as pharmacologic treatments for
obesity or overweight with comorbidities.
• Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (GIP), both
incretin hormones inactivated by dipeptidyl peptidase-4 (DPP-4), stimulate insulin secretion
after an oral glucose load via the incretin effect.
• In type 2 diabetes, this process can become blunted or even be absent; however, the
utilization of pharmacological levels of GLP-1 can revive insulin excretion.
G l u c a g o n - l i k e Pe p t i d e - 1 ( G L P- 1 )
Agonists
• The benefits of this form of therapy to treat type 2 diabetes include delayed gastric
emptying and inhibiting the production of glucagon from pancreatic alpha cells if
blood sugar levels are high.

• GLP-1 receptor agonists can decrease pancreatic beta-cell apoptosis while promoting
their proliferation.

• Lowering both systolic and diastolic blood pressure and total cholesterol.

• Can improve left ventricular ejection fraction, myocardial contractility, coronary blood
flow, cardiac output, and endothelial function while reducing infarction size and overall
risks for a cardiovascular event.
G l u c a g o n - l i k e Pe p t i d e - 1 ( G L P- 1 )
Agonists
• Increased glucose uptake in the muscles, decreased glucose production in the liver,
neuroprotection, and increased satiety due to direct actions on the hypothalamus.

• Lower all-cause mortality as well as hemoglobin A1c reduction.

• Many formulations of GLP-1 agonists, all of which historically were injectable and
administered subcutaneously due to poor oral bioavailability.

• Recently, the FDA approved an oral formulation of semaglutide.

• Single or multi-dose pens, may need to separate prescription for needles (

semaglutide includes needles- Ozempic).
G l u c a g o n - l i k e Pe p t i d e - 1 ( G L P- 1 )
Agonists
• Dulaglutide - once weekly

• Albiglutide - once weekly

• LIRAGLUTIDE - ONCE DAILY

• SEMAGLUTIDE - ONE WEEKLY SUBCUTANEOUSLY, DAILY ORALLY

• Exenatide BID - twice daily

• Exenatide QW - once weekly

• Lixisenatide - once daily

• Tirzepatide - once weekly

Adverse Effects/ Side Effects
• Nausea, vomiting, diarrhea that could lead to an acute kidney injury.

• Dizziness, mild tachycardia, infections, headache, dyspepsia

• Hypoglycemia ( low risk)

• Patients should receive counseling that this class of drugs increases satiety, and
transient, mild nausea may occur if they attempt to eat while feeling full.

• Increasing the dosage of these medications should occur slowly if nausea is present.
Injection-site pruritus and erythema are also common, most notably with the longer-
acting medications in this class
Contraindications
• Pregnancy ( recommend contraception for women using it)

• Hypersensitivity

• Patients with GI diseases ( inflammatory bowel disease, gastroparesis)

• In animal studies- Thyroid gland C-cells and tumors.

• Personal or family history for multiple endocrine neoplasia 2A, 2B or medullary throid
cancer.
• Acute pancreatitis ( including potentially fatal hemorrhagic and necrotizing types)

• Patients with pancreatitis or pancreatic cancer

• Patients with severe renal dysfunction.

G l u c a g o n - l i k e Pe p t i d e - 1 ( G L P- 1 )
Agonists
• Some patients may find it difficult to accept
injectable therapy

• GLP-1 agonists only stimulate β-cells to

produce insulin when glucose levels are
elevated, when used as monotherapy there is
minimum risk of hypoglycaemia.

• Semaglutide greater weight loss than others

(tirzapatide better than semaglutide 1 mg)

• Expensive

• Counsel on how to use pens

Administration
• Check the pen

• Insert needle

• Confirm the flow

• Set up drug metering ( 0.6, 1.2, 1.8, 2.4,

3 mg )

• Inject ( wait about 6 seconds)

• Remove the needle

Storage
• After the first use pens can stay in room temperature for 30 days ( saxenda), 56
days ( ozempic).

• Should stay refrigirated before the first use. ( 2-8 C).

• Do not share needle

• Do not use same needle again

Semaglutide (Ozempic)
• 0.25, 0.5, 1 mg

• Start with 0.25 mg once- a week for first 4 weeks

• Stay 0.5 mg once-a week for at least 4 weeks

• 1 mg for at least 4 weeks

• May be increased to 2 mg for additional control

Semaglutide (Rybelsus)
• Start from 3 mg ( 4 weeks)

• Increase to 7 mg ( 4 weeks)

• 14 mg

• Take on empty stomach, wait at least 30

mins before eating, drinking or taking
another medication.

• If patient miss a pill, skip and take one

tablet the morning after
Setmelanotide
• Setmelanotide is a melanocortin-4 (MC4)
receptor agonist used to treat obesity caused by
genetic proopiomelanocortin (POMC), proprotein
convertase subtilisin/kexin type 1 (PCSK1), or
leptin receptor (LEPR) deficiencies or Bardet-
Biedl syndrome
 Bariatric Surgery

➢ Indications:

– BMI > 40 kg/m2

– BMI > 35 kg/m2 with co-morbidities of obesity (hypertension, severe diabetes, sleep apnea, osteoarthritis)
– BMI > 30 kg/m2 with type 2 diabetes, refractory to treatment measures or dysmetabolic syndrome X
– Failure of conservative attempts at weight loss

• Psychological screening recommended before undergoing surgery

• Best means to cure obesity-related complications (hypertension, diabetes)

• Surgical options:

– Sleeve gastrectomy
– Roux-en-Y gastric bypass
– Laparoscopic gastric band
– Intragastric balloon

• Weight loss of up to 40% of baseline weight may be seen at 12–18 months after the procedure.
Bariatric care
• After bariatric surgery, patients use medications short-term and long-term;

• Omeprazol- 6 months after surgery or indefinitely

• Ursodiol- reduce the risk of gallstones due to rapid weight loss

• Multivitamins and calcium; depending on the type of surgery, may be for some time or life-
long.
• NSAIDs should be avoided ( increase the risk of stomach ulcers). Gastric bypass patients
should avoid indefinitely.
• Antihypertensive and diabetes medication dosages can be changed after surgery.

• Tablets can not be absorbed short-term after surgery so capsule & liquids are preffered.
Bariatric care
• Daily caloric intake should be between 500 and 700 calories for at least the first 12
months after surgery, not exceeding 1,000 calories a day.

• 60-80 mg protein a day.

• Women of childbearing years to use an effective birth control option, such as an

intrauterine device (IUD), for the first 12 to 18 months following bariatric surgery.
During this time, the rapid weight loss and inability to consume normal food quantities
impact a patient's nutritional status. The physical demands of a pregnancy in the first
year after surgery can compromise fetal health and result in birth defects.

• Liquid food, soft food and then transition to regular food.

Long-term Follow -up
• 2,6 and 12 months after surgery.

• Followed –up annualy.

• Exercise, healthy diet should be maintained or weight gain can happen.

✓ Complete blood count (which can reveal anemia, among other problems)
✓ Comprehensive metabolic panel (which gives information related to kidney and liver
function)
✓ Lipid panel (which measures cholesterol and other fats)
✓ Hemoglobin A1c (a test for diabetes)
✓ Vitamins: Iron, ferritin, B12, D, A, folate, thiamine, copper, zinc and selenium