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obese women injecting drug


Eli Lilly's tirzepatide received a much-anticipated weight loss indication, making it the third GLP drug approved for obesity; Saxenda was approved in 2014 and Wegovy in 2021. In its pivotal study, tirzepatide caused an average weight loss of 21% at its highest dose (15 mg), which is greater than that seen with Wegovy (16%) and Saxenda (8%). The diabetes version of tirzepatide is Mounjaro, while the weight-loss version will be marketed as Zepbound. Both drugs have the same prescribing information, with identical dosage forms and dosing ranges.

Given the popularity of Wegovy, Zepbound is sure to be a blockbuster. Hopefully, Eli Lilly is more prepared than Novo Nordisk, which has been unable to meet Wegovy demand, leaving many patients in limbo.

These highly-effective weight loss medications are on track to become one of the biggest drug classes ever. Right now, insurance coverage and costs are barriers for many. But oral versions are coming down the pipeline, which will help lower prices through competition and cheaper manufacturing.

woman taking morning after pill


Emergency contraception, also known as the morning-after pill, can be taken up to five days after unprotected intercourse to help prevent pregnancy. A common regimen is a single 1.5 mg dose of levonorgestrel, marketed as Plan B One-Step® and available over the counter to anyone 17 and older.

NSAIDs, which block prostaglandins necessary for ovarian follicle rupture, have been shown to inhibit ovulation in studies. A recent trial (N=860) published in the Lancet found that adding a single 40 mg dose of the long-acting NSAID piroxicam (half-life 50 hours) to levonorgestrel 1.5 mg within 72 hours of unprotected intercourse lowered the absolute risk of pregnancy by 1.5% (1 vs 7 pregnancies, 0.2% vs 1.7%, p=0.036).

While the absolute risk reduction was only 1.5%, when talking about unwanted pregnancies, the consequences are life-changing. Most emergency contraception is obtained over the counter, and piroxicam is only available by prescription. The question then arises as to whether an OTC NSAID like naproxen would have the same effects. One can't say for certain, but naproxen is generally safe in young, healthy patients, so advising women to take it for 3 - 4 days with levonorgestrel seems prudent, given the potential benefit.
Another study finds antibiotics have no meaningful benefit in sinusitis
sick child blowing his nose
In the U.S., 17 million antibiotic prescriptions are written annually for sinusitis, contradicting evidence from placebo-controlled trials that have consistently shown they have no meaningful effect on outcomes. A recent study published in the JAMA randomized 515 children aged 2 to 11 with persistent (symptoms > 11 days) or worsening (symptom increase on days 6 - 10) sinusitis to Augmentin or placebo. The primary outcome - average daily symptom score (range 0 - 40 with higher scores meaning worse symptoms) - was 9.04 in the Augmentin group and 10.6 in the placebo group (p<0.001), which translates to a 3.9% difference. Clinically significant diarrhea was more common in the Augmentin group (11% vs 5%, p=0.005).

This study only enrolled patients with persistent or worsening infections, scenarios where antibiotics are supposed to be more effective. Despite this, symptoms were only 4% better, while significant diarrhea was 6% greater. Trials in adults are even less impressive. Patients like antibiotics, and providers like happy patients, so it's unlikely another marginal study will change prescribing habits. But at least providers who decline antibiotics have another study to back their decision.

pregnant women receiving vaccine


Abrysvo, a new RSV vaccine recently approved in adults 60 and older, has received an indication in pregnancy to prevent RSV infections in newborns. It is the second therapy in recent months approved for this purpose; the antibody nirsevimab (Beyfortus) discussed below is the other treatment. The effects of Abrysvo were evaluated in a randomized controlled trial (N=7358) detailed at the link below.

CDC recommends antibody to prevent RSV in infants
infant getting its nose suctioned
The CDC recently recommended that all infants younger than 8 months, born during – or entering – their first RSV season (typically fall through spring) receive one IM dose of nirsevimab (Beyfortus®), a monoclonal antibody against RSV. Additionally, they recommend infants 8 to 19 months at high risk for severe RSV receive a dose in their second season. In a 150-day placebo-controlled study involving healthy infants born ≥ 35 weeks gestation (N=1490), nirsevimab lowered the absolute risk of symptomatic RSV infection by 3.8% (p<0.001) and hospitalization for RSV by 1% (p=0.07). In a similar study with preterm infants born 29 to <35 weeks (N=1453), nirsevimab lowered RSV infections by 6.9% (p<0.001) and hospitalizations by 3.3% (p<0.001). Eight deaths occurred across both studies (nirsevimab - 5, placebo - 3); none were deemed related to the vaccine or RSV.

Nirsevimab had a marked benefit in preterm infants, while its effects in those born ≥ 35 weeks gestation were less pronounced, only reducing RSV hospitalizations by a statistically nonsignificant 1%. A fair question to ask is whether healthy term infants who are infected and achieve natural immunity are better protected in the long run than those who receive nirsevimab. The CDC is always quick to recommend preventive therapies, even when the overall benefits are questionable. Parents should be given meaningful information as opposed to blanket recommendations so they can make informed decisions.


Levemir to be discontinued in the U.S. in 2024

Levemir symbol
Novo Nordisk announced it will discontinue Levemir insulin in the U.S. starting in 2024. Levemir Flexpen will see supply disruptions beginning in mid-January and will be discontinued on April 1st. Levemir vials will be discontinued on December 31, 2024.

Another intermittent fasting study shows no benefit over usual eating

picture of plate with a clock on it
Intermittent fasting (IF), a fad diet where eating is restricted to certain hours of the day, has shown no benefit over usual eating in two randomized controlled trials and a small effect in another. A fourth trial comparing it to a calorie-restricted diet (25% energy restriction daily) and a control diet (no calorie or time restrictions) in 90 obese adults found that it was no better than calorie restriction for weight loss over 12 months (IF - 4.87% loss, calorie restriction - 5.3% loss).

FDA approves islet cell therapy for type 1 diabetes

picture of diabetic checking blood sugar
The FDA approved donislecel (Lantidra®), a pancreatic islet cell therapy derived from deceased donors, for the treatment of adults with Type 1 diabetes who are unable to approach target HbA1c because of current repeated episodes of severe hypoglycemia. The therapy is delivered via portal vein infusion, and recipients require long-term immunosuppression. Up to three infusions may be given, depending on the patient's response. In two studies involving thirty patients, insulin independence was achieved in 17 subjects for an average of 3 to 5 years.

New opioid antagonist nasal spray coming soon

picture of pills opioid pills and heroin
A new opioid antagonist called Opvee® (nalmefene) was recently approved to treat opioid overdose. It is a nasal spray similar to Narcan that comes in a single-use spray device. One notable difference between the drugs is their half-lives - 11.4 hours for Opvee and 1.85 hours for Narcan. Opvee's longer half-life may mean it requires less repeat dosing for longer-acting opioids; however, a potential downside is opioid withdrawal symptoms, which may last longer with Opvee relative to Narcan.

Another vitamin D study finds no effect on fractures

hip bone with osteoporosis
Vitamin D fanatics tout it as a cure for almost everything, but even studies in bone health, where a benefit seems most logical, have consistently found supplementation does not improve outcomes. The latest negative trial enrolled over 20,000 elderly adults and randomized them to vitamin D3 60,000 IU once monthly or placebo. After a median follow-up of 5.1 years, there was no significant difference between groups for incident fracture (5.6% for vitamin D3 vs 5.9% for placebo).



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Limited study finds testosterone does not increase CVD risk, raises other concerns
elderly man lifting weights
Testosterone replacement therapy (TRT) has become its own industry, with providers and clinics dedicated solely to its promotion and distribution. Randomized trials evaluating long-term TRT effects are lacking, and the risks of potential adverse events (e.g. prostate cancer, thromboembolism) are mostly unknown. Cardiovascular disease (CVD) is a significant concern, as TRT has been shown to accelerate atherosclerosis in small studies. To evaluate the effects of TRT on CVD events, the TRAVERSE study randomized 5246 men with testosterone levels < 300 ng/dl and established CVD or multiple CVD risk factors to testosterone gel (titrated to serum level of 350 - 750 ng/ml) or placebo. After an average follow-up of 33 months, the incidence of the primary outcome, a composite of CVD events, was similar between groups (TRT - 7%, Placebo - 7.3%).

This study was framed as positive and "reassuring" by many news outlets and TRT proponents, but it has limitations. The average treatment period was only 22 months, and the median testosterone level in the TRT group was 371 ng/dl, meaning half of the participants were below or at the bottom of the target range. Furthermore, arrhythmia requiring intervention (5.2% vs 3.3%), atrial fibrillation (3.5% vs 2.4%), and acute kidney injury (2.3% vs 1.5%) occurred significantly more in the TRT group. The effects of TRT on hypogonadism symptoms (e.g. ED, mood, libido) were also analyzed, and those findings will be released in a future publication. Sixty-one percent of TRT-treated patients discontinued their therapy early, so it will be interesting to see what those results show.

Colchicine approved to prevent cardiovascular disease (CVD)
ECG, stethoscope, and pills
Colchicine, an antiinflammatory drug used for decades to treat gout, was recently approved to prevent CVD events in patients with established CAD or multiple CAD risk factors. Approval was based on the LoDoCo2 trial where 5522 patients with stable CAD were randomized to colchicine 0.5 mg once daily or placebo. After a median follow-up of 29 months, a composite outcome of cardiovascular events (MI, CVD death, stroke, revascularization) occurred in 6.8% of the colchicine group and 9.6% of the placebo group (difference 2.8%, p<0.001). A similar study ( COLCOT trial | N=4745) had comparable findings in patients with recent MI (5.5% vs 7.1%, difference 1.6%, p=0.02).

Colchicine had a modest effect on CVD in the LoDoCo2 and COLCOT trials, reducing the absolute risk of CVD events over 2 - 3 years by 1 - 3%. It had no significant effect on mortality in either trial, and noncardiovascular death was higher in colchicine-treated patients in the LoDoCo2 trial (1.9% vs 1.3%, HR 1.51 95%CI [0.99 - 2.31]); the reason for this is unclear, as there were no apparent trends in the individual causes of death. Colchicine side effects, including diarrhea, were similar to placebo, and an increased risk of myopathy from combining colchicine with statins - a common drug interaction warning - was not observed.

Colchicine for CVD prevention may be a logical option for certain high-risk CVD patients, particularly those with gout; however, the increased risk of noncardiovascular deaths in the LoDoCo2 trial is concerning. The 0.5 mg dose, which has been given the trade name Lodoco, is not available yet, but the 0.6 mg dose is widely prescribed and has a cheap generic.


A 55-year-old female with depression comes to see you about her medication. She has been taking Zoloft for five years and has had no depressive episodes in the last three. She is thinking about stopping the Zoloft and wants to know what your advice is.

Should you recommend against it, or tell her it's worth a try? Are there any studies that offer guidance on the issue? See the link below for more.