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Aug 24, 2018

Drop down

The story

Like even the best of residents, weight loss meds start strong but burn out over time. Can semaglutide trigger more durable responses?

The basics

One way to help patients lose weight is to zap appetite. Liraglutide has other fancy endocrine effects (we're told), but there's nothing like the drug's chief side effects – nausea, vomiting, and diarrhea – to make a burger and supersize fries seem less appealing. The injectable GLP-1 agonist is one of 5 FDA-approved weight loss drugs, each of which plateaus after a one-time loss of around 6 - 8% of bodyweight. Hopes are higher for semaglutide, liraglutide's long-acting cousin that was approved last year for glycemic control in diabetes.

The phase 2

Patients on high dose semaglutide dropped weight at a pace never seen before with medication, says a phase 2 study of 1,000 obese, non-diabetic patients (BMI > 30). Participants were assigned to liraglutide, placebo, or one of 7 dosing semaglutide dosing strategies. The largest dose produced an average weight loss of 14% at 52-weeks (see dose response curves), and responses appeared to be ongoing at the end of the study period. Like liraglutide, over 90% of patients had unpleasant GI side effects.
Lancet

The takeaway

Semaglutide appears promising for patients who can stomach it. Several phase 3 studies are underway, and a pill version of the drug is in clinical trials.

Say it on rounds

When your ABG gets lost in the tube system...again

Time to switch up the approach. A phase 3 trial evaluated ibalizumab, a first-in-class antibody that disables HIV cell entry by blocking CD4, in 40 patients with multi-drug resistant HIV. Despite viral loads > 1000 copies/mL on optimal standard therapy, more than 80% of patients responded to treatment within 2 weeks and 50% achieved viral loads < 200 copies/mL at the end of the study period. Results from 48-week follow-up are up next.
NEJM

When changing times call for changing care

Many transgender women choose to use estrogen to align their physical appearance with their gender identity. An EMR-based cohort study of 2,800 trans-women found higher rates of venous thromboembolism and ischemic stroke compared to cisgender women, including cis-women on hormone replacement therapy. Rates of myocardial infarction were similar to matched cisgender male controls. The findings call for more research into the vascular effects of cross-sex estrogen.
Annals

When early discharge leads to end-of-shift admissions

It's easy to connect cause and effect. An population analysis of high income countries found a decline in life expectancy in the US and the UK between 2014 - 2016. At 79 years, the US ranked last in life expectancy among the countries studied, while Japan led the pack with a life expectancy of 84 years. Drug overdose, suicides, and other so-called "deaths of despair” in younger individuals drove much of the excess US mortality. 
BMJ

Brush up

Tumor lysis syndrome

Anything that prompts massive cell breakdown can cause tumor lysis syndrome (TLS). So while TLS is the most common disease-related emergency for leukemia and lymphoma, bulky or extensively-metastasized tumors also pose a risk. Complications include severe kidney injury, cardiac dysrhythmias, and neuromuscular irritability. Extensive fluids and use of uric-acid lowering agents are key for management and prophylaxis. 

What's the evidence

For rasburicase in TLS? Every attending has their own threshold for when they choose to use the recombinant enzyme to lower uric acid instead of the cheaper and more widely available allopurinol. A 2017 retrospective study of 130 patients with clinical or laboratory confirmed TLS found that patients treated with rasburicase had lower length of stay and lower inpatient costs than patients treated with allopurinol. If you plan to use rasburicase, make sure to check for G6PD deficiency to avoid rasburicase-induced hemolytic anemia.

What your public health friends are talking about

Guns and abortion are old news, but it turns out that Russian trolls also had a thing for vaccines. Experts say the trolls used fake accounts to legitimize the vaccination debate as a means of sowing discord.

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