Three GLP-1 drugs, Zepbound (tirzepatide), Wegovy (semaglutide), and Saxenda (liraglutide), are currently approved for weight loss. Zepbound and Wegovy have demonstrated superior weight loss (16% to 22%) compared to Saxenda (8%), making them two of the most discussed medications in decades. Now, they have been compared head-to-head in an open-label trial, where 751 overweight, nondiabetic adults were randomized to Zepbound (target dose 10 mg or 15 mg/week) or Wegovy (target dose of 1.7 mg or 2.4 mg/week). The primary outcome, percent change in weight from baseline to week 72, was -20.2% with Zepbound and -13.7% with Wegovy (p<0.001). Key secondary outcomes, including average weight loss (50 lbs vs 33 lbs) and the proportion of participants achieving a weight reduction of 20% or more (48% vs 27%), also favored Zepbound. Side effects, including nausea (44% vs 44%), constipation (28% vs 29%), diarrhea (24% vs 23%), and vomiting (15% vs 21%), were similar between groups and mainly occurred during the therapy titration phase. Drug discontinuation due to adverse events was slightly higher in the Wegovy group (6.1% vs 8%).

These results corroborate findings from placebo-controlled studies, which showed that both drugs are highly effective, but Zepbound is superior. Patients sometimes ask me if one of the two has fewer side effects, and I can now confidently say they are similar in that regard. For those who are unaware, current cash pricing for both drugs is detailed below.

• 2.5 mg: $349 per month
• 5 mg: $499 per month
• 7.5 mg: $499 per month
• 10 mg: $499 per month

Wegovy cash pay: Novo Nordisk now offers all doses of Wegovy for $499/month through their online mail-order pharmacy NovoCare Pharmacy. Wegovy is available from other pharmacies for $650/month with the Wegovy savings card.

• Zepbound vs Wegovy for Weight Loss in Obese Adults, NEJM (2025)
• Zepbound review
• Wegovy review
• Article on webpage

Gepotidacin (Blujepa) is a new antibiotic approved for uncomplicated female UTIs in adult and pediatric patients 12 years of age and older weighing at least 88 lbs (40 kg). It is a first-in-class triazaacenaphthylene antibiotic that works by inhibiting bacterial DNA gyrase and topoisomerase IV, essential enzymes for bacterial DNA replication. Its efficacy was evaluated in two randomized, noninferiority trials comparing gepotidacin (1500 mg BID for 5 days) to nitrofurantoin (100 mg BID for 5 days) in females with uncomplicated UTIs. In Trial 1 (N=634), the composite response rate (clinical cure and microbiological eradication at Day 10 to 13) was 51.8% for gepotidacin and 47.0% for nitrofurantoin, with a treatment difference of 5.3% (95% CI: -2.4, 13.0). In Trial 2 (N=567), the composite response rates were 58.9% and 44.0%, respectively, with a treatment difference of 14.4% (95% CI: 6.4, 22.4). Common side effects include diarrhea (16%), nausea (9%), and abdominal pain (4%). Gepotidacin is a sensitive CYP3A4 substrate and should not be taken with strong CYP3A4 inhibitors or inducers. It also inhibits acetylcholinesterase, which may cause it to potentiate the effects of other acetylcholinesterase inhibitors (e.g., donepezil) and reduce the efficacy of anticholinergics (e.g., benztropine, oxybutynin). It comes in a 750 mg tablet, and the recommended dosing is 1500 mg (two 750 mg tablets) twice daily for 5 days, taken after a meal.

Another possible use for gepotidacin, treatment of Neisseria gonorrhea, was evaluated in a randomized trial. The EAGLE-1 study (N=628) compared gepotidacin (two 3000 mg doses 10-12 hours apart) to intramuscular ceftriaxone 500 mg plus oral azithromycin 1 g for uncomplicated urogenital gonorrhea in patients 12 years of age and older weighing at least 88 lbs (40 kg). Microbiological cure rates at Days 4 - 8 were 92.6% for gepotidacin and 91.2% for ceftriaxone/azithromycin, demonstrating noninferiority of gepotidacin. Gastrointestinal side effects were more common in the gepotidacin group.

Like all new drugs, gepotidacin will be too expensive to be considered first-line for UTIs. However, its efficacy in gonorrhea is intriguing, given the increasing resistance of this bacterium to available therapies. A study of its effects in drug-resistant gonorrhea would be informative.

• Gepotidacin (Blujepa) review
• Gepotidacin vs Nitrofurantoin for Female UTI, Lancet (2024)
• Gepotidacin vs Ceftriaxone + Azithromycin for Gonorrhea, Lancet (2024)
• Article on webpage

Low-dose aspirin is currently recommended as monotherapy to reduce atherosclerotic events in patients with chronic coronary disease (CCD). To explore the effects of other antiplatelet agents, researchers in South Korea performed SMART-CHOICE 3, a randomized, open-label study that compared clopidogrel 75 mg daily to aspirin 100 mg daily in 5506 high-risk CCD patients who had completed standard dual antiplatelet therapy after PCI. Over a median follow-up of 2.3 years, the primary outcome, a composite of death from any cause, myocardial infarction, or stroke, occurred in 4.4% of the clopidogrel group and 6.6% of the aspirin group (hazard ratio 0.71 [95% CI 0.54-0.93]; p=0.013). There was no significant difference in bleeding risk. 

These findings align with a previous 2021 study, HOST-EXAM (N=5438), which similarly found clopidogrel monotherapy superior to aspirin for preventing a composite of CVD events in South Korean patients (5.7% vs 7.7%, p=0.003). Despite these results favoring clopidogrel, the 2023 AHA CCD guidelines, published after HOST-EXAM but before SMART-CHOICE 3, still recommend aspirin as first-line therapy. The authors cite weaknesses in HOST-EXAM, including its open-label design, homogenous South Korean population (high CYP2C19 loss-of-function allele prevalence), and low event rate, as reasons for sticking with aspirin. Until updated guidelines are published, it is unclear if SMART-CHOICE 3 will change this position.

• SMART-CHOICE 3 - Clopidogrel vs Aspirin in High-risk CCD Patients, Lancet (2025)
• HOST-EXAM - Clopidogrel vs Aspirin for CCD after PCI and 6 - 18 Months of DAPT, Lancet (2021)
• AHA 2023 CCD recommendations
• Article on webpage

Bacterial vaginosis (BV), affecting up to 30% of young women, has a high recurrence rate, with over 50% of women experiencing reinfection within 12 weeks. The cause of BV is poorly understood, but women who report sex with a regular partner have twice the risk of those who are not sexually active. This observation has led to speculation that the condition is sexually transmitted. However, previous studies where females and their male partners were treated with oral therapy have not demonstrated a reduction in recurrence. One possible explanation for these findings is that oral therapies alone may not be sufficient to clear cutaneous penile carriage of bacterial vaginosis–associated organisms. To test this theory, Australian researchers randomized monogamous couples in which the woman had BV to female-only treatment (female-only group) or female and male partner treatment (partner-treatment group). In both groups, females received metronidazole 400 mg twice daily for 7 days or intravaginal metronidazole or clindamycin if contraindicated. In the partner-treatment group, males received the same metronidazole regimen along with 2% clindamycin cream applied to the penile skin twice daily for 7 days. During follow-up, females were tested for BV at day 8, week 4, week 8, week 12, and as needed for symptoms. At study conclusion, the primary outcome, BV recurrence within 12 weeks, was significantly lower in the partner-treatment group compared to the female-only group (35% vs 63%, p<0.001)

This study provides some insight into BV and sexual transmission. It also raises the question of whether topical therapy alone in male partners, including over-the-counter creams like Neosporin, could reduce recurrence. Lastly, it's important to note that 35% of women in the partner-treatment group had a recurrence, suggesting that some type of underlying predisposition plays a significant role in BV susceptibility.

• Male-Partner Treatment to Prevent Recurrence of Bacterial Vaginosis, NEJM (2025)
• Genitourinary infections
• Article on webpage

Spinal injections, frequently performed in pain medicine practices, are a common intervention for chronic back pain, with an estimated 9 to 11 million injections performed annually in the US alone. Despite their widespread use, studies examining their efficacy have been mixed, with placebo-controlled trials typically finding no effect. [PMID 21914755, PMID 24988555] To further explore the issue, the British Medical Journal convened a panel comprising four patients with chronic spine pain, 10 clinicians experienced in managing chronic spine pain, and eight methodologists. The group reviewed randomized controlled trials and observational studies involving spine procedures and issued the following recommendations:

• The following procedures have no proven benefit and should not be offered for radicular or axial spine pain in the cervical or lumbar region:
• Epidural injection of local anesthetic, steroids, or their combination
• Joint radiofrequency ablation with or without joint targeted injection of local anesthetic plus steroid
• Joint-targeted injection of local anesthetic, steroids, or their combination
• Intramuscular injection of local anesthetic with or without steroids
• Dorsal root ganglion radiofrequency with or without epidural injection of local anesthetic or local anesthetic plus steroids

These recommendations contradict those of the American Society of Interventional Pain Physicians (ASIPP), a professional organization that represents pain management physicians. The 2021 ASIPP guidelines strongly endorse spinal injections for treating chronic lumbar and cervical pain. In their discussion, the ASIPP authors argue that saline or short-acting local anesthetics, frequently used as controls in steroid injection studies, shouldn't be considered placebos because they have an actual therapeutic effect. They go on to contend that single-arm analysis (i.e., looking at therapies individually without comparing them to a control group) is most telling and should receive the majority of emphasis. Huh?

While it's a little comical and slightly disconcerting that a professional association would make an argument to disregard placebo controls in randomized trials, it's not surprising given that they represent doctors who put their kids through college performing these procedures. It also explains how two professional organizations can come to entirely different conclusions analyzing the same evidence. Like most things in life, all you have to do is follow the money.

• BMJ Practice Guideline on Interventional Procedures for Chronic Spine Pain (2025) [PubMed abstract]
• Low back pain review
• Article on a webpage