A recording of this presentation is available HERE.
Trauma Informed Care (Lund, 3/26/2025)
A recording of this presentation is available HERE.
Thanks so much to Dr. Erin Lund for a very impactful presentation this week on Trauma Informed Care. I have to confess that I have seen this presentation (or a previous version) before, but I DO need to hear and rehear and rehear this topic.
If you remember nothing else, take pearl in: In our daily work should use "universal trauma principles" with ALL patients and then add "extra carefuly trauma informed care" with those whom we KNOW have had extra trauma.
This includes things like asking for consent, empowering patients over their own bodies and histories, and resisting retraumatization.
I love/hate this image she shared, reminding us of the context of trauma that extends far beyond a person's individual experience. The medical trauma many of our patients have experienced primes them to respond in particular ways to our care provision, and we need to be prepared, but the collective and structural trauma is also ever present.
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© Lewis-O’Connor, A. 2015 © Rittenberg, E 2015 © Grossman, S. 2015 UPDATED, April 2020, Feb 2022 |
Trauma abounds.
Many of us are well-versed in the original Adverse Childhood Events (ACES) study, which found that 61.7% of CA adults had experienced at least one ACE, and 1 in 6 (16%) had experienced 4+ ACES. You can see the most common ACEs in the image below.
The actual "traumatic experience or incident" matters much less than how we respond to the trauma. What are our resources? Do we have resilience? What are our protective patterns? Do we have time to recover?
The image below is a schematic of a stress trigger, the natural response, and then what follows. Note the time of calming down, depletion and recentering. If we have the tools to pass through these stages, we can recover from the trigger. If not, we may not be able to. Traumatic experiences can lead to developing toxic stress physiology. And repeated stress can impact our neurodevelopment, interfering with executive function
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www.dovetaillearning.org |
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Toxic Stress and Caring Adults - KABOOM! |
A local non-profit does trainings/workshops to promote resilience. In their workshops, they teach us that our protective patterns, which we develop over time, can be helpful and keep us safe. But when overused or used in incorrect situations, they can be harmful, self-destructive, and inhibit connection with others. Those patterns are seen in the slide below:
SAMSHA (2021) says that to be trauma-informed we must 1) Realize the widespread impact of trauma and understand potential for recovery 2) Recognize the signs/symptoms of trauma 3) Respond by integrating this knowledge about trauma into policies and procedures and practices and 4) Seek to active Resist retraumatization.
We can create a safe context, restore power, value individuals. We can use universal trauma precautions and stay patient-centered. Being trauma-informed in the medical setting involves empowering patients, giving choice when we can, collaborating, offering safety and trustworthiness. In addition, get curious, learn the back story, listen to patients' fears. Ask yourself and the patient, "How can we help you get through this?"
Resilience is protective. I very much recommend you listen to Dr. Lund's presentation, where she goes on to really talk about heartfelt listening, growing empathy to connect, not defining people by their trauma, and making a real difference through trauma-informed care.
She ended her presentation with a seminal paper on Trauma informed care in the ED from Ashworth et al (2023). A link to that paper and very helpful tables is available HERE.
Pediatric Ophthalmology (Qureshi, 3/19/25)
A recording of this presentation is available HERE.
My notes:
In pediatric patients, any condition that affects the amount of light passing through the eye will negatively affect the brain's ability to learn and see and result in permanent vision loss.
Therefore, it is essential to treat pediatric eye disorders as quickly as possible!!
Common causes of childhood blindness, worldwide
- corneal scarring
- vitamin A deficiency
- measles
- opthalmia neonatorum
- harmful eye practices
- infective corneal ulcers
- congenital cataracts
- uncorrected refractive errors
- retinopathy of prematurity
- congenital glaucoma
WHO estimates 19 million visually impaired children worldwide, 1.4 million preventable blindness
Common pediatric eye disorders
- Amblyopia: a decrease in visual development that occurs when the brain doesn't get visual stimulation from the eyes (one or both eye send distorted image to brain, even when glasses are use). Only children get amblyopia, can result in permanent vision loss if not treated in child. Most common cause of vision loss in adults 20-70 is untreated amblyopia
- refractive amblyopia is treatable with glasses/patching
- patch the good eye, let the bad eye function, it works! but does not fix strabismus
- alternatively, drop of atropine in the good eye, to allow bad eye to see better (limits vision in good eye to a certain amount)
- deprivation amblyopia: if you have cataract or congenital ptosis blocking the pupil, very bad for visual development (poor prognosis within even 6 weeks, e.g. cataract, corneal ulcer, congenital ptosis)
- the primary care physician detects amblyopia (e.g. red light reflex), ophthalmology treats it
- asymmetric red light reflex>> urgent eval < 6 weeks of age
- Strabismus: ocular misalignment, "to squint or look obliquely", affects 4% of children <6 years, 30-50% results in reversible amblyopia (vision loss)
- strabismus testing: light reflex is the key (see image below)
- pseudostrabismus: looks like esotropia but light reflex is centered on the pupils (common in kids of Asian descent)
- surgical repair
- Congenital Cataracts: 1/3 hereditary, 1/3 associated with other disorder, 1/3 idiopathic
- must remove within 3 months to prevent irreversible vision loss
- Congenital Ptosis: must be able to see pupil, if kid is using a chin up position, vision is not a threat (ptosis is there, but vision is safe)
- Horner Syndrome: when you see ptosis, check the pupils. The ptotic eye (SNS innervates the eyelid mm but also the iris dilator), if pupil assymetry with ptosis, patient needs brain/neck/upper chest imaging to follow nerve plexus to make sure there is no problem along the plexus causing the ptosis (e.g. tumor)
- Nevus of Ota: low percentage develop glaucoma (see R eye below, grey in sclera and skin)
- Congenital Glaucoma: enlarged cornea, tearing eyes, spasmodic to light, can develop serious vison loss, need urgent treatment. Very different than an adult. In a kid you should be able to see swollen cornea, almost like a corneal ulcer or maybe like one eye is bigger than the other. Should be referred urgently
- Retinoblastoma of childhood
- most common ocular tumor or childhood
- usual onset < 4 years
- 25% present with strabismus
- treatment: radiation, chemo, possibly enucleation
- require systemic work up, including r/o pineal gland and bone tumors
- Red eyes
- Nasolacrimal duct obstruction is very common, usually presents as tearing, common, 5% of newborns,
- no rush to refer >>90% regress by 12 months (95% by 18 months)
- surgical treatment occurs 18-24 months w/nasolacrimal probe
- Dacryocystocoele (image below): within first few weeks of life, infection and bump w/preseptal cellulitis due to imperforate valve. Have to treat preseptal cellulitis with IV abx and then sedate and probe. It looks better after abx butu if you don't create the passage, it will recur.
- Blepharitis: Very common, redness in conjunctiva and redness in eyelids>> treat the eyelids (warm compresses, abx drops despite no infection> glands work and eyes work better). Can also have stye. Erythromycin ointment doesn't work, but Maxitrol drops do work.
- Neonatal conjunctivitis: neonatal gonorrhea (very violent, first day of life), chlamydia, chemical, HSV (4-5 weeks of life).
- need systemic treatment AND ointment
- Allergic conjunctivitis: itchy red eyes, papillae, zaditor drops OR systemic allergy treatment, temporary steroids okay w/taper if really bad
- vernal conjunctivitis is severe form of allergic, can lead to shield ulcers, giant papillae, often in young men
- Styes: obstruction of meibomian glands, very common
- hordoleum is a blocked gland
- chalazion is the more chronic granulomatous form
- warm compresses, maxitrol (neomycin/polymyxin/dexamethasone) ointment, only if superinfection can consider antibiotic
Direct visual acuity screening is gold standard
- Start screening age 3/4 w/HOTV or heart/house/square tools for refractive problems
(Tumbling E hard to do with young kids)
- Age 4-5, use HOTV card but can use "match card", looking for 20/40 vision (doesn't have to be better), one eye should NOT be way better than the other> this should trigger referral
- Age 5+, looking for 20/30 or better, move to Sloan Letters and repeat q1-2 years
Phenobarbital for Severe Alcohol Withdrawal Syndrome (Aguilar & Bowen 3/12/2025)
A recording of this presentation is available HERE.
My notes:
- 10.9% of US adults have alcohol use disorder (AUD) at some point in their lifetime (!!)
- AUD costs the US $249 billion/year
- 178,000 excess deaths due to AUD in the US 2021
- Compared to opioids, higher rates of alcohol use, misuse, ED visits, and deaths see below)
Alcohol Withdrawal Syndrome (AWS)
- 500,000/year episodes of AWS requiring pharmacological treatment
- 5-20% of people admitted to the hospital have AWS
- highest risk of seizures in first 1-2 days of AWS, DTs 4-6 days with looooooooong tail
- Reminder of difference between hallucinosis vs. DTs (autonomic instability)
Neuropharmacology of Alcohol
Dopamine>> reward>> addiction
GABA agonism during intoxication>> sedation
Chronic use>> GABA downregulation, Glutamate upregulation
Lots of other neurotransmitters involved: opiate R, serotonin R, cannabinoid R, etc
When we take away alcohol (after chronic use), our GABA system is completely depleted, and our glutamate is "going wild"
Phenobarbital is a barbiturate
- GABA agonism, suppresses glutamate
- PO>> onset 60 minutes, IV>> onset 5 minutes
- metabolized in the liver, excreted renally
- 1/2 life ~79 hours (range 53-118 hours)
- this prolonged half life allows for a built in taper
- has a predictable pharmacokinetics at 10mg/kg (deal body weight), though no RCTs that study "ideal drug level" for AWS
- no documented barbiturate resistant alcohol withdrawal
Traditional treatment of AWS is with benzodiazepines. We know benzos can cause paradoxical agitation and delirium. In addition, a lack of endogenous GABA in chronic alcohol use can make benzos less useful.
What does the current literature say about Phenobarbital vs benzos?
- Retrospective cohort study, 42-bed ICU, 120 participants (2018, Am J of Critical Care)
- shorter ICU stays (2.4 vs 4.4), shorter hospital stays (4.3 vs 6.9). lower rate of mechanical ventilation (2% vs 23%), fewer adjunctives including precedex (7% vs 28%)
- RCT with ED pts requiring admission – single dose phenobarb vs symptom-based BZD, 102 participants (2013 Journal of Emergency Medicine)
- decreased ICU admission rates (8% vs 25%), decreased BZD use
- Retrospective cohort over 2 years, 606 participants (2021, Cureus)
- shorter hospital stay (2.8 vs 3.6), lower all-cause 30-day readmission (11% vs 19%), fewer 30-day ED visits
- 2 different Metanalyses (2021) findings: may shorten hospital LOS, unclear if shortens ICU LOS but does decrease ICU admission, benzo sparing, may result in less intubation
Some suggestion that we should move away from CIWA for scoring AWS. One proposed alternative is RASS scoring, which should be familiar to people who work in ICUs
Proposed Phenobarbital Protocol DRAFT
Notes:
- For HIGH risk patients (CIWA>20 OR CIWA>16 with Risk factors)
- 10-12 mg/kg (IDEAL body weight) loading dose
- Use ideal body weight calculator (MD Calc)
- should happen in monitored setting (ED vs. ICU) only
- For patients who may be at lower risk for AWS, consider lower dose than the loading dose (e.g. 130mg, 260mg IV/IM) q30 minutes-1 hour
- Patients who have already been treated with benzos CAN receive phenobarbital but should be lower dose (due to risks of sedation)
References:
SAMHSA Center for Behavioral Health Statistics and Quality. (2022). National Survey on Drug Use and Health (Table 5.9A—Alcohol use disorder in past year: among people aged 12 or older; by age group and demographic characteristics, numbers in thousands, 2021 and 2022, Issue. https://www.samhsa.gov/data/sites/ default/files/ reports/ rpt42728/NSDUHDetailedTabs2022/NSDUHDetailedTabs2022/NSDUHDetTabsSect5pe2022.htm#tab5.9a
Centers for Disease Control and Prevention. (February 29, 2024). Excessive Alcohol Deaths. Retrieved April 1 from https://www.cdc.gov/alcohol/features/excessive-alcohol-deaths.html#:~:text=About%20178%2C000%20people%20die%20from,or%20488%20deaths%20per%20day
Fixed-Dose Phenobarbital Versus As-Needed Benzodiazepines for the Management of Alcohol Withdrawal in Acute Care General Internal Medicine https://pubmed.ncbi.nlm.nih.gov/38151248/#:~:text=There%20was%20no%20difference%20in,%25%2C%20P%20%3D%200.03).
National Institute on Alcohol Abuse and Alcoholism. (2024). Alcohol-related emergencies and deaths in the United States. Retrieved April 1 from https://www.niaaa.nih.gov/alcohols-effects-health/alcohol-topics/alcohol-facts-and-statistics/alcohol-related-emergencies-and-deaths-united-states
Maldonado, J. R. (2017). Novel Algorithms for the Prophylaxis and Management of Alcohol Withdrawal Syndromes-Beyond Benzodiazepines. Crit Care Clin, 33(3), 559-599.
Tidwell, W. P., Thomas, T. L., Pouliot, J. D., Canonico, A. E., & Webber, A. J. (2018). Treatment of Alcohol Withdrawal Syndrome: Phenobarbital vs CIWA-Ar Protocol. Am J Crit Care, 27(6), 454-460.
Rosenson, J., Clements, C., Simon, B., Vieaux, J., Graffman, S., Vahidnia, F., . . . Alter, H. (2013). Phenobarbital for Acute Alcohol Withdrawal: A Prospective Randomized Double-blind Placebo-controlled Study. The Journal of Emergency Medicine, 44(3), 592-598.e592.
Hawa, F., Gilbert, L., Gilbert, B., Hereford, V., Hawa, A., Al Hillan, A., . . . Al-Sous, O. (2021). Phenobarbital Versus Lorazepam for Management of Alcohol Withdrawal Syndrome: A Retrospective Cohort Study. Cureus, 13(2), e13282.
Murphy, J. A., Curran, B. M., Gibbons, W. A., & Harnica, H. M. (2021). Adjunctive Phenobarbital for Alcohol Withdrawal Syndrome: A Focused Literature Review. Annals of Pharmacotherapy, 55(12), 1515-1524.
Hammond, D. A., Rowe, J. M., Wong, A., Wiley, T. L., Lee, K. C., & Kane-Gill, S. L. (2017). Patient Outcomes Associated With Phenobarbital Use With or Without Benzodiazepines for Alcohol Withdrawal Syndrome: A Systematic Review. Hospital Pharmacy, 52(9), 607-616.
Chagas Disease: Why a Neglected Tropical Disease Matters for US Clinicians (Heindel, 3/5/25)
A recording of this presentation is available HERE.
Dr. Leah Heindel gave a wonderful Grand Rounds presentation this week on Chagas Disease. Perhaps the most important moment of the presentation was this slide:
Family medicine, indeed, is all of these.
Epidemiology and Disease Burden
Chagas Disease, which infects 7-8 million people worldwide, mostly in Latin America, presents a health burden seven times higher than malaria in the Western Hemisphere. There are an estimated 300,000 people living in the US with Chagas disease, many of whom are immigrants from Mexico, El Salvador, Guatemala, and Honduras. Unfortunately, only about 1% of those have been identified. Both vector and vertical transmission occurs in the US (22-100 cases congenital chagas in the annually).
Chagas disease has both an acute and indolent phase. The overwhelming majority of people infected with Chagas disease (90%) will be asymptomatic in the acute phase, but chronic impacts (especially GI, cardiac) typically appear 20-30 years after initial infection.
Seroprevalence in immigrants from endemic countries is believed to be about 1% in the general population, though it varies widely depending on how these estimates are made. For example, you can see in the table below from the IDSA that there is a MUCH higher seroprevalence in immigrant patients from endemic areas with otherwise unexplained non-ischemic cardiomyopathy (13-19%).
Vertical transmission occurs in 2-13% of cases, most congenital infection is asymptomatic, but Chagas has been associated with preterm delivery, low birthweight and low APGAR scores.
Clinical manifestations
Chagas disease is generally spread via the bite of the "kissing bug", usually on the neck and face at night while people are sleeping; the same bug defecates close to that area, then the disease is transferred to the bloodstream via scratching at the site and introduction of bug feces to the broken skin. The acute phase of Chagas (only in about 10% of people infected) presents as a non-specific viral syndrome, including fever malaise, and anorexia. One pathognomonic sign of acute Chagas is Romaña's sign, pronounced swelling of the eyelid (as seen in image below). Domesticated and farm animals serve as reservoirs of the disease, and thatched roofs are a known risk factor in endemic areas.
Screening during pregnancy has been shown to be cost effective and may be something we should be integrating locally in our at-risk population-- more on this to come. Options for pregnancy-screening include pre-pregnancy screening (this MOST preferred because cannot treat during pregnancy) vs. routine OB screening vs. L&D serum IgG vs. newborn cord blood or PCR and even the possibility of universal newborn screening.
After decades long latency, most common manifestations include cardiac (sudden cardiac death as #1 cause of death from Chagas, 55-60% of people, also HFrEF (25-30%) and embolic disease (10-15%). It seems that the parasite has a particular predilection for the electrical and conducting system.
GI effects are also well-documented and occur in 10-21% of people with chronic Chagas, including both esophageal and colonic manifestations. In the esophagus, dysphagia and regurgitation are common; in the colon sigmoid rectal dilatation and progressive constipation.
Neurologic effects including peripheral neuropathy and even dementia have been suggested. In addition there is a reactivation syndrome that can affect people with transplant or other immunosuppression.
Screening and Diagnosis
The earlier Chagas is detected, the better the outcomes. Once someone has chronic cardiac or GI effects, treatment has shown to be unhelpful.
Diagnosis is done via is a serum IgG test with reflex to confirmation (goes to CDC), which is available through most laboratories.
Both the CDC and IDSA recommend targeting screening based on risk factors, in particular being born in or lived in endemic areas, having a family member with Chagas Disease.
Screening during pregnancy has been shown to be cost effective and may be something we should be integrating locally in our at-risk population-- more on this to come. Options for pregnancy-screening include pre-pregnancy screening (this MOST preferred because cannot treat during pregnancy) vs. routine OB screening vs. L&D serum IgG vs. newborn cord blood or PCR and even the possibility of universal newborn screening.
Diagnostic testing is warranted in patients who come from endemic areas AND present with electrocardiogram abnormalities (wide range, including 1st degree AV block, afib, PVCs, RBB, low voltage), thromboembolic phenomenon, HFrEF otherwise unexplained, and megacolon or megaesophagus.
Treatment
There are two approved treatments for Chagas Disease, both for extended duration (see image below for dosing)
1) Benznidazole x 60 days
2) Nifurtimox 90 days
Both treatments have high side effect profiles (GI, CNS, marrow suppression). They are contraindicated in pregnancy, though safe in lactation, and contraindicated in severe hepatic and renal dysfunction. These medications also may be hard to come by locally.
Finally, Dr. Heindel recommends this book, The Kissing Bug, written by a first generation immigrant journalist and author, whose family was directly impacted by this disease and who follows the socio and geopolitical forces that influence the management of Chagas in the US immigrant population today.
Medical Aid in Dying (Rubin 2/26/2025)
A recording of this presentation is available HERE.
Many thanks to Dr. Rebecca Rubin for an excellent talk on Medical Aid in Dying (MAID), California's legislation, which allows patients with terminal illness (<6 month prognosis) to request and be prescribed medication to self-administer to end their own life.
This was a fantastic presentation that included the history of physician-assisted suicide and euthanasia as well as present moral and ethical challenges. Do watch if you have 45 minutes!
My notes from this presentation:
Documentary: How to Die in Oregon (2011) follows the stories of terminally ill patients in Oregon as they navigate physician assisted suicide.
Medical aid in dying, in which a patient must self-administer lethal medications, is not the same as physician-assisted suicide, in which a physician does the administration.
And yet, MAID is still controversial, brings up many social, cultural and ethical issues, including:
- patient autonomy (the right to make this choice)
- beneficence (do no harm)
- the ethical difference between prescribing medication to end someone's life vs. withdrawing life-sustaining care
- physician patient relationship
Medical Aid in Dying was legalized in California via the "End of Life Options Act", which took effect in June 2016. This followed Oregon's law, "Death with Dignity" which passed in 1997.
The AMA has formally opposed "assisted suicide" since 1993. This was affirmed in 2018 in a close vote. In the same year (2018), the AAFP broke ranks with the AMA and took a position of "engaged neutrality" and deemed the decision a personal one between a physician and patient.
Reasons patients choose MAID from a 2024 Oregon survey, The Commpasion and Choices Meidcal Aid in Dying Utilization Report:
- loss of autonomy (91.6%)
- loss of dignity (63.8%)
- control of bodily functions (46.6%)
- burden on others (43.3%)
- pain control (34.3%)
- finances (8.2%)
The most common illnesses for which people request MAID are cancer>> neurodegenerative>> cardiovascular disease. BUT disproportionate % of people with ALS choose MAID
-88% of people who choose MAID are simultaneously in hospice
-men=women (no data on non-binary, trans)
-disproportionate rates of white and college educated patients
-while rates are rising in BIPOC, still much lower than white
There are currently 11 states in the USA that legally permit MAID (see image)
There are also different policies and procedures, most notably in Europe, but also in parts of Latin America and Oceania (see image)
In California, patients must:
- Independently and voluntarily request info from two providers
Prescriber and consulting physician
- Some states require written request with witnesses
- Mandatory waiting period of 2-15 days
- Terminal illness, life expectancy <6 months
- Be over the age of 18
- Have the mental capacity to make decision
- Physically be able to self-administer meds into GI tract
The Netherlands and Switzerland are both known for more liberal policies around death and dying in patients with terminal illness
- In the Netherlands, this includes: the possibility of either medical aid in dying OR physician assisted suicide, services available to patients > 12 years old
Access can be an issue:
- Medication costs ~$600-$800
- Independent physicians (private pay) charge between $2000 and $3000 for their services
- Health plans are not required to cover
- SNFs have varying rules about what can happen in their facilities
In SoCo, there are 6-7 current consulting physicians but not many prescribers
Kaiser has a robust internal referral system
Some religious intuitions forbid discussing MAID with patients
There does exist the Sonoma County End of Life Doula Initiative. "Death Doulas" help patients and families prepare for death, including planning end of life celebrations, discussing fear, writing stories, etc
Which medications?
Standard medication before 2016 was secobarbital, a potent barbiturate with a time to death that averages 30 minutes. Since 2016, a cocktail that includes medications that decrease respiratory drive, cause an arrythmia, suppress escape rhythm (+nausea meds). See slide below for dosing.
One of the current areas of controversy in MAID is assistance for "psychological suffering"-- in the Netherlands, there have been increasing numbers of patients receiving MAID for mental illness (though rates are still very low-- 95% of people who apply are rejected).
Conclusions:
MAID is legal in 10 states plus Washington D.C.
Criteria for MAID:
Independently and voluntarily request info from two providers
Life expectancy<6mo
Waiting period 2-15
Have capacity
Self-administer into GI tract
Medication protocol: DDMAPh (digoxin 100mg, diazepam 1gm, morphine 15mg, amitriptyline 8gm, phenobarbital 5gm)
Resources:
ACAMAID for more information for clinicians and patients, https://www.aadm.org/
Compassion and Choices for Advocacy, https://compassionandchoices.org/
Advancements in GLP-1 Receptor Agonists: Where we are and where we're going (Felton, 2/19/25)
A recording of the presentation is available HERE.
***
Many thanks to Dr. Erin Felton for an excellent presentation on a hot topic: GLP-1 Receptor Agonists, the class of medications that is literally taking our nation by storm. As Dr. Felton said during her presentation, direct to patient advertising and word of mouth has led to droves of patients coming to their providers asking for these medications, most commonly, for weight loss.
A recording is available above.
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| comorbidities associated w/obesity |
Here are my notes:
- obesity is a chronic, relapsing , treatable multifactorial disease
- it is associated with comorbidities (e.g. HF, DM2, uterine cancer) and complications
- BMI, as we know, is not a perfect measure, but it's what we currently have
- According to 2023 CDC data: 1/5 US adults are obese
- By 2030, there are estimates that 1/3 US adults will have a BMI>30
- There are racial and socioeconomic disparities associated with obesity
- these are particularly evident in communities of color (black and Latinx)
We must be aware of our own "fat bias" in medicine
- always ask patients for permission before discussing their weight
- give patients a right to decline weighing in
- focus on chronic disease aspect of obesity (rather than weight)
- consider how to create a supportive environment for obese patients
There are several FDA approved medications for obesity, the GLP-1 Receptor Agonists are the new kids on the block, but see the image below for all meds that are currently approved for long-term usage, short-term usage, and off label usage:
GLP-1 is an endogenous incretin hormone that is produced by the L cells in the distal ileum and colon in response to food intake. GLP-1 receptor agonists mimic this mechanism. In addition, GLP-1 receptors are expressed in multiple organs: GI tract, pancreas, hypothalamus, brainstem, heart, kidney, muscle, fat cells. It is thought that effects on the brain influence appetite and satiety. Receptors in the GI tract decrease gastric emptying and slow gastric motility.
Current GLP-1 Receptor Agonists:
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Murphy EJ,”What’s new in Endocrinology”, Medical Management of HIV Conference, 2024 |
The newer kid on the block are multi-targeted incretin therapies, including GIP, which is secreted more proximally in the small intestine; it stimulates downstream GLP-1, enhances insulin, promotes satiety and seems to be associated with less nausea.
The newest agent, tirzepatide, is a combo of GIP/GLP-1. There are currently two versions of tirzepatide on the market: Mounjaro (indication: DM) and Zepbound (indication: weight loss). Zepbound is currently covered by Partnership medi-cal.
Current combos/multi-targeted incretin therapies:
Specific prescribing info for semaglutide and tirzepatide:
There are no direct head to head trials comparing semaglutide to tirzepatide.
Indirect comparisons suggest more weight loss with tirzepatide, as well as potentially lower side effect profile.
Side Effects
We should definitely be talking to our patients about side effects when we are prescribing these medications.
The most common side effects of GLP-1 medications are GI symptoms (nausea, vomiting, constipation, etc). GI symptoms are extremely common (25-40%) but do decrease over time. In many trials, a large percentage of people self-discontinued the medications due to side effects.
Going slow can mitigate the GI side effects, as they do abate over time. Reducing meal size and adopting a low fat (and low glycemic index) diet can also reduce side effects. Patients should have some nutritional counseling (even if it's just from the PCP). Increasing fiber may also help.
Dizziness and dehydration have also been reported. This could be due to morning hypoglycemia. Small frequent meals and maintaining good hydration are recommended.
As mentioned above, the newer combination medications MAY be better tolerated.
Contraindications:
Contraindications to these medications include: medullary thyroid cancer/MEN2, pregnancy, hx pancreatitis or gallstone disease (relative/not absolute). Of note, there was some post-marketing signal in 2023 suggesting a correlation with suicidality, further assessment in 2024 did not confirm this signal, but consider ongoing assessment in patients with a hx of depression or SI.
Starting/stopping
There is good evidence that discontinuing GLP-1 meds lead to gaining back a large percentage of weight that was lost (though overall, pts do maintain a small percentage of weight lost). A retrospective cohort study of 125K patients, just released in 2025 found that 53% of patients and 72% of patients had discontinued these medications at 1 and 2 years, respectively. Somewhere between 1/3 and 1/2 of these patients resumed these medications within 1 year of stopping.
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| Wilding et al, Step 1 Extension, Diabetes Obes Metab 2022 |
About insurance:
- Medicare specifically does NOT cover weight-loss drugs. However, as of 3/24, Medicare will cover semaglutide for obese patients for CVD prevention IF they have documented CVD (e.g. prior MI, PVD, etc)
- Only about 20% of Medicaid programs cover weight loss drugs (Medi-Cal does! See the image below showing the current PHP covered medications)
- Only about 25% of employer-based insurance cover weight loss drugs
- Locally, Kaiser does NOT cover weight-loss drugs unless you have another specific indication (e.g. DM2, HFrEF, CVD)
- There has been varying pharmacy supply
Patient Counseling pearls
- There is significant weight regain after discontinuation of GLP1s, though studies so far have still showed a net loss.
- Most patients who newly initiate treatment with GLP RA discontinue within 2 years.
- High burden of GI side effects, gets better with time.
- Need for long term therapy due to weight regain?
- Other factors for adherence: high cost, availability of medication
- All studies done at target dose of 2.4mg
Finally, there are more and more studies being published showing benefit in outcomes other than weight loss. These include CVD, OSA, MASN/MAFLD, dementia, Parkinson's, disease, as well as substance use disorder. Stay tuned.
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