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FEATURED

WEGOVY TABLETS NOW AVAILABLE

woman holding Wegovy tablets and injector
The introduction of the Wegovy (semaglutide) tablet marks a significant milestone in obesity management, offering the first oral GLP-1 receptor agonist approved for weight loss. Patients who dislike injecting themselves now have a proven GLP option. Like its injectable counterpart, the tablet works by mimicking the GLP-1 hormone to regulate appetite and food intake.

In trials, Wegovy injections caused an average of 13-16% weight loss over 68 or more weeks, depending on the study. The Wegovy pill has been studied in one small trial (N=307), where it led to an average weight loss of 13.6% over 64 weeks. Notedly, Novo Nordisk has been advertising 17% weight loss with the pill in what it calls a "trial-product estimand" that estimates the pill's efficacy if every subject had adhered perfectly to therapy. This outcome is biased because it excludes patients who stopped the medication due to adverse events, lack of effectiveness, or a combination of the two. The pill's side effects are mainly gastrointestinal and similar to the shot. One side effect unique to the pill is dysesthesia (sensitive skin, hyperesthesia, and skin burning sensations), which was reported by 5% of subjects. The pill is taken once daily on an empty stomach in the morning with water, and patients should not eat or drink for 30 minutes afterwards. This may not be as convenient as the once-weekly injection for some patients.

Current pricing for each therapy is outlined below. It's likely GLP therapy prices will continue to decline, as Eli Lilly is set to release its own pill in the near future.

Wegovy injection
  • 0.25 mg and 0.5 mg: $199/month for new patients, otherwise $349/month
  • 1.0 mg, 1.7 mg, and 2.4 mg: $349/month

Wegovy pills
  • 1.5 mg: $149/month
  • 4 mg: $149/month for new patients, otherwise $199/month
  • 9 mg and 25 mg: $299/month

Lerochol (Lerodalcibep): a new PCSK9 inhibitor
illustration of a heart
PCSK9 is an enzyme that binds to LDL receptors on the surface of liver cells and promotes their degradation. PCKS9 inhibitors are antibodies that bind PCSK9, reducing its activity and increasing the number of receptors available to clear LDL cholesterol from the bloodstream. When added to statin therapy, these agents typically lower LDL cholesterol levels by approximately 50% to 60%. Two PCSK9 inhibitors are currently available: Praluent (alirocumab) and Repatha (evolocumab). Now, a third agent, Lerodalcibep (Lerochol), has been approved.

Like its predecessors, Lerochol significantly lowers LDL-C levels, with clinical trials showing reductions similar to those achieved with alirocumab and evolocumab (LDL reductions of 50-60%). It's dosed once monthly as a subcutaneous injection into the abdomen or upper thigh. No studies have been completed evaluating its effects on clinical outcomes.

COFFEE AND ATRIAL FIBRILLATION: NEW STUDY CHALLENGES CAFFEINE CONCERNS

Cup of coffee with a heart shape in the foam
For decades, conventional wisdom has held that coffee and caffeine act as triggers for heart rhythm disorders, particularly atrial fibrillation (AF). Patients with arrhythmias are routinely advised to avoid caffeinated beverages to reduce the risk of palpitations and AF episodes. This belief stems mainly from the known stimulant effects of caffeine and anecdotal patient reports. However, scientific evidence supporting this theory has been inconsistent. While caffeine can acutely raise heart rate, several large observational studies have actually suggested a neutral or even protective association between regular coffee consumption and the development of AF. Until recently, randomized clinical trial data to definitively settle this debate has been lacking.

The DECAF (Does Eliminating Coffee Avoid Fibrillation?) randomized clinical trial, published in JAMA in 2025, sought to address this gap. The study enrolled 200 adults who were regular coffee drinkers and had a history of persistent AF or atrial flutter. Following successful electrical cardioversion to restore normal sinus rhythm, participants were randomly assigned to either continue drinking caffeinated coffee (at least one cup daily) or to completely abstain from all coffee and caffeine products for six months. The primary outcome was the clinically detected recurrence of AF or atrial flutter. Surprisingly, the group randomized to coffee consumption experienced significantly fewer arrhythmia recurrences. Specifically, AF or atrial flutter recurred in 47% of the coffee consumption group compared to 64% of the abstinence group. This difference translated to a 39% lower hazard of recurrence for those who continued drinking coffee (Hazard Ratio 0.61; 95% CI, 0.42-0.89; P=.01). Adherence to the study protocols was good, with the coffee group consuming a median of 7 cups per week and the abstinence group reducing intake to near zero.

These findings directly contradict the long-standing assumption that coffee worsens AF. The authors suggest several potential mechanisms for this protective effect, including caffeine's blockade of adenosine receptors (adenosine can promote AF), coffee's anti-inflammatory properties, and potential diuretic effects. While the study had some limitations, such as its open-label design and modest sample size, it provides the strongest evidence to date that moderate caffeinated coffee consumption is safe and potentially beneficial for patients with atrial fibrillation. For patients who enjoy their daily cup, these results offer reassurance that coffee does not need to be on the restricted list.
Beta-blockers in coronary artery disease without heart failure
heart illustration
The historical paradigm of recommending beta-blockers for all post-myocardial infarction (MI) patients arose from trials predating modern acute coronary syndrome (ACS) management. With widespread adoption of early revascularization (PCI or CABG) and intensive secondary prevention pharmacotherapy, the incidence of heart failure (HF) and severely reduced left ventricular ejection fraction (LVEF) following MI has significantly decreased. This improvement in acute care has raised questions about the necessity of long-term beta-blocker therapy for patients with coronary artery disease (CAD) who maintain a preserved or mildly reduced LVEF (≥ 40%) and no other primary indication.

Four recent randomized controlled trials have explored this issue, yielding conflicting results. The BETAMI-DANBLOCK study (N=5574, duration 3.5 years) reported a modest, yet statistically significant, benefit for beta-blockers, finding a lower risk of death or major adverse cardiovascular events (14.2% vs. 16.3%; HR 0.85; p=0.03). Conversely, the large REBOOT-CNIC (N=8505, median duration 3.7 years) and REDUCE-AMI (N=5020, median duration 3.5 years) studies found no significant benefit of long-term beta-blocker therapy on their respective composite endpoints. Lastly, the ABYSS study (N=3698, median duration 3 years), which enrolled stable patients already on therapy, found that beta-blocker interruption was not noninferior to continuation (HR 1.16; p=0.44 for noninferiority).

Collectively, the results from these trials do not make a strong case either for or against the continued, routine use of beta-blockers in post-MI patients with preserved LVEF and no other compelling indications (e.g., angina, atrial fibrillation, uncontrolled hypertension). While the BETAMI-DANBLOCK suggests a small benefit and ABYSS cautions against stopping therapy in stable patients, the overall lack of robust, consistent benefit in the major trials does not support the uniform use of beta-blockers in this patient population. Current guidance reflects this evolving evidence, leaning toward reassessing the long-term need for beta-blockers after the first year post-MI in the absence of reduced LVEF or other indications.

SECOND NEUROKININ RECEPTOR ANTAGONIST APPROVED FOR MENOPAUSAL HOT FLASHES

woman with hot flash
Lynkuet (elinzanetant), a nonhormonal treatment for vasomotor symptoms (VMS) due to menopause, was recently approved by the FDA. It is the second drug approved in the neurokinin (NK) receptor antagonists class, following Veozah (fezolinetant), approved in 2023. The drugs differ slightly in their NK receptor binding; Veozah selectively binds NK3 receptors while Lynkuet binds NK1 and NK3 receptors. During menopause, estrogen withdrawal increases neurokinin activity in the brain's thermoregulatory center, and NK receptor antagonists suppress neurokinin secretion.

In their respective phase 3 trials, both agents demonstrated a statistically significant reduction in VMS frequency and severity (≥ hot flashes over 24 hours) compared to placebo. In two 12-week trials, the placebo-subtracted reduction in VMS episodes (baseline ∼ 11 episodes/day) with Veozah was about 2.5 per 24 hours. Similarly, the placebo-subtracted reduction in VMS episodes (baseline ∼ 14 episodes/day) with Lynkuet was about 3.2 per 24 hours in 12-week trials. Notably, across all trials, the placebo group experienced reductions of 4 to 6 episodes per day, suggesting a significant psychological component in VMS improvement. Common side effects for both agents include gastrointestinal issues like abdominal pain and diarrhea, as well as nervous system effects such as insomnia, back pain, and headache. Lynkuet's label notes a central nervous system (CNS) depressant effect, with somnolence and dizziness occurring in ≥ 5% of patients. Veozah has a Boxed Warning for hepatotoxicity, with transaminase elevations >3X ULN reported in 2.3% of women in pooled clinical trials. In Linkuet trials, transaminase elevations ≥ 3X ULN occurred in 0.6% of Lynkuet-treated women and 0.4% of placebo-treated women. Both manufacturers recommend monitoring liver function tests during therapy. A major difference in drug-drug interactions stems from different metabolic profiles: Veozah is a CYP1A2 substrate and is contraindicated with CYP1A2 inhibitors, while Lynkuet is primarily metabolized by CYP3A4 and requires dosage modification or avoidance when used with CYP3A4 inhibitors or inducers.

Women suffering from menopause-related VMS now have two nonhormonal options; however, both medications are significantly more expensive than hormone replacement therapy (HRT) and often require prior authorization along with stepped therapy for insurance coverage. A study comparing Veozah or Lynkuet to HRT would be informative.
Targeting high-normal potassium levels in patients with implantable cardioverter–defibrillators (ICD)
ecg with stethoscope
Hypokalemia and low-normal potassium levels (<4.0 mEq/L) are known risk factors for ventricular arrhythmias in patients with cardiovascular disease. Consequently, maintaining high-normal potassium levels (4.5 - 5 mEq/L) in these patients may be beneficial. To examine the issue, researchers performed the POTCAST trial, where 1200 patients with an ICD (underlying heart disease: heart failure - 64%, ischemic heart disease - 50%, nonischemic cardiomyopathy and primary arrhythmia disorders - 50%) and a potassium of less than 4.3 mEq/L were randomized to a target potassium level of 4.5 to 5.0 mEq/L (high-normal group) or standard care. In the high-normal group, potassium levels were increased using potassium supplements, mineralocorticoid receptor antagonists (spironolactone or eplerenone), or both. Guidance on a potassium-rich diet was also provided, and potassium-losing diuretics were stopped if able. After a median follow-up of 39.6 months, the primary outcome (a composite of documented sustained ventricular tachycardia or appropriate ICD therapy, unplanned hospitalization for arrhythmia or heart failure, or death from any cause) was significantly lower in the high-normal group compared to standard treatment (22.7% vs 29.2%, P=0.01) Appropriate ICD therapy or documented ventricular tachycardia and unplanned hospitalization for arrhythmia accounted for the majority of the difference in the primary end point. Hospitalization for hyperkalemia or hypokalemia was similar between groups.

The protocol for achieving the target range included initial visits every other week for blood tests and medication adjustments. The median duration for this intensive adjustment period was 85 days. Despite this rigorous protocol, only 42% of participants in the high-normal potassium group achieved a target potassium level. This type of frequent monitoring would be impractical in most routine outpatient practices. However, this study does offer an important takeaway: the beneficial effect was not dependent on achieving the high-normal target, suggesting the goal should be to avoid hypokalemia or low-normal potassium levels in this patient population.

NEWS IN BRIEF

Mounjaro receives FDA indication for type 2 diabetes in pediatric patients

Mounjaro box
The U.S. Food and Drug Administration (FDA) has expanded the indication for Mounjaro (tirzepatide) to include the treatment of type 2 diabetes in pediatric patients aged 10 to 18 years. This approval marks a significant advancement in the management of youth-onset type 2 diabetes, a condition that has historically had few effective treatment options compared to adult-onset diabetes. Prior to this new indication, Bydureon and Victoza were the only two GLP-1 receptor agonist therapies approved for use in children.

The approval is based on positive results from the SURPASS-PEDS clinical trial, where 99 children aged 10 to 18 years with type 2 diabetes inadequately controlled with metformin and/or basal insulin (mean age 14.7 years | mean A1C 8%) were randomly assigned to receive tirzepatide (5 mg or 10 mg) or placebo. After 30 weeks, the pooled Mounjaro group demonstrated a mean reduction in Hemoglobin A1C of 2.23%, whereas the placebo group saw an increase of 0.05%. In addition to glycemic improvements, the drug showed significant benefits for weight management. Patients in the 5 mg and 10 mg Mounjaro groups experienced BMI reductions of 7.4% and 11.2% respectively, compared to a negligible 0.4% reduction in the placebo group.

ACOG Recommends Treating Male Partners for Bacterial Vaginosis

clue cells
The 2025 StepUp randomized clinical trial, published in the New England Journal of Medicine, provided compelling evidence for treating male partners of women with recurrent bacterial vaginosis (BV). The study enrolled 164 monogamous couples where the female partner had symptomatic BV. In the treatment arm, women received standard guideline-based therapy, while their male partners were treated concurrently with oral metronidazole (400 mg twice daily) and topical 2% clindamycin cream applied to the penis twice daily for 7 days. The control group consisted of women receiving standard therapy while their partners received no treatment. The trial was stopped early for efficacy after an interim analysis of 150 couples. In the primary analysis, BV recurrence at 12 weeks occurred in 35% of women in the partner-treatment group compared to 63% in the control group (P<0.001). This represents a significant reduction in recurrence risk, challenging previous assumptions that partner treatment is ineffective.

In response to these findings, the American College of Obstetricians and Gynecologists (ACOG) issued a Clinical Practice Update in December 2025. The new guidance recommends that clinicians consider concurrent sexual partner therapy with the combination of oral and topical antimicrobials for male partners of patients with recurrent, symptomatic BV. This marks a significant shift from previous guidelines, which generally did not recommend partner treatment. Ideally, this strategy applies to women in monogamous relationships, aligning with the trial's eligibility criteria. The update emphasizes the importance of shared decision-making for patients who may not fit this specific profile, such as those with a first occurrence of BV or non-monogamous partners.

Semaglutide in schizophrenia patients

Wegovy box
Semaglutide is FDA-approved for the treatment of type 2 diabetes and chronic weight management. However, its use in specific vulnerable populations has been less explored. Individuals with schizophrenia are particularly susceptible to metabolic disturbances, often exacerbated by treatment with second-generation antipsychotics (SGAs). These medications, while essential for psychiatric stability, significantly increase the risk of obesity and prediabetes, contributing to a reduced life expectancy in this patient population.

To evaluate the effects of semaglutide in schizophrenia, researchers performed the HISTORI study, where 154 SGA-treated adults with schizophrenia, prediabetes, and obesity were randomized to semaglutide (up to 1.0 mg weekly) or placebo. After 30 weeks, patients receiving semaglutide achieved a mean reduction in HbA1c of 0.38% compared to an increase of 0.08% in the placebo group (p<.001). Additionally, the semaglutide group experienced a substantial mean body weight loss of 9.04 kg, while the placebo group gained 0.17 kg (p<.001). Gastrointestinal side effects like nausea were more common with semaglutide but diminished over time, and no subjects in either group discontinued therapy because of side effects. Importantly, semaglutide did not affect mental health or quality of life.

These findings provide reassuring evidence that semaglutide can be safely used to address critical metabolic health needs in patients with schizophrenia without compromising their mental health stability.

High-dose Wegovy may be coming soon

Wegovy box
Wegovy (semaglutide) is currently approved for chronic weight management at a maximum weekly dose of 2.4 mg. Studies have shown this dose causes average weight loss of 13% to 16%, an effect that is less than the 20% to 22% seen with its primary competitor, Zepbound (tirzepatide). To evaluate whether a higher dose of Wegovy is more effective, researchers performed the STEP UP trial, where 1407 obese adults were randomized to Wegovy 7.2 mg, Wegovy 2.4 mg, or Placebo. Over 72 weeks, mean weight loss was 18.7% in the Wegovy 7.2 mg group, 15.6% in the Wegovy 2.4 mg group, and 3.9% in the placebo group (p<0.0001). Gastrointestinal side effects were more common in the 7.2 mg group compared to the 2.4 mg group (70.8% vs 61.2%). Dysaesthesia, an unpleasant and often painful sensation, such as burning or tingling under the skin, was also more common in the 7.2 mg group (22.9% vs 6.0%).

Novo Nordisk has submitted a supplemental New Drug Application to the FDA for the 7.2 mg dose. The company hopes to receive an expedited review period of one to two months, potentially making the high-dose option available in early 2026.

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Study finds extended anticoagulation beneficial after provoked venous thromboembolism (VTE)
leg dvt
Current treatment guidelines for provoked VTE (i.e., VTE after immobilization, surgery, extended travel, or pregnancy) recommend three months of anticoagulation. Anticoagulation beyond three months (extended anticoagulation) is typically reserved for patients with strong, persistent VTE risk factors, including active cancer or thrombophilia. The effects of extended anticoagulation on patients with provoked VTE who have minor chronic VTE risk factors (e.g., obesity, CVD) are unknown. To explore this clinical gap, researchers performed the HI-PRO trial, where 600 adults with provoked VTE and minor chronic VTE risk factors were randomized to 12 months of apixaban (2.5 mg twice daily) or placebo after completing at least 3 months of anticoagulation. The prevalence of minor risk factors and results after one year were as follows:
  • Chronic VTE risk factors: Chronic inflammatory or autoimmune disorder - 52%, Obesity - 48%, CVD - 29%, Chronic lung disease - 22%, Chronic kidney disease - 11%
  • Symptomatic recurrent VTE: Apixaban - 1.3%, Placebo - 10% (P<0.001)
  • Major bleeding: Apixaban - 0.3%, Placebo - 0% (P>0.999)

In the HI-PRO trial, extended anticoagulation was superior to three months of anticoagulation in patients with provoked VTE who had minor chronic risk factors for recurrence (55% of participants had two or more risk factors). The first-year VTE recurrence rate in the placebo group was 10%, which is notably higher than the 1–6% rate observed in other studies enrolling patients with provoked VTE. The unexpectedly high placebo recurrence rate and the resulting clinical benefit from extended anticoagulation suggest that current risk stratification models may underestimate the impact of less significant chronic risk factors (e.g., chronic inflammatory disorders, CVD, obesity) when determining the need for indefinite anticoagulation following a provoked VTE. One limitation of the study is the 12-month treatment duration, which may not reflect the full risks and benefits of lifelong anticoagulation. It will be interesting to see how future guidelines incorporate data from this study. In the interim, providers may consider discussing the implications of this study with patients who present with provoked VTE and coexisting minor, long-term risk factors for recurrence.

Study evaluates stopping anticoagulation in atrial fibrillation treated with catheter ablation
heart and doctor
Catheter ablation has become a common treatment for atrial fibrillation (AF), and many patients undergo the procedure in hopes of stopping anticoagulation. Catheter ablation success, defined as no atrial arrhythmias, depends on the type of AF and the length of follow-up. One-year success rates for paroxysmal AF are 70% to 85%, while persistent AF has a success rate of 50% to 70%. Over longer follow-up periods, success rates decline. Since catheter ablation is not 100% curative, and AF can come and go without symptoms, stopping anticoagulation after the procedure may increase stroke risk. Conversely, continuing anticoagulation increases bleeding risk. To examine the issue, researchers performed the ALONE-AF trial, where 840 patients (median CHA2DS2-VASc score of 2) with AF who had undergone catheter ablation and had no documented AF recurrence for at least one year were randomized to continuing anticoagulation (with apixaban or rivaroxaban) or stopping it. No atrial arrhythmia recurrence was documented with ECGs and at least two sessions of 24- to 72-hour Holter monitoring, with at least one performed within two months of enrollment. After two years, the primary outcome, a composite of stroke, systemic embolism, and major bleeding, was observed in 0.3% of the discontinue group and 2.2% of the continue group (P=0.02). Stroke was seen in 0.3% and 1.4%, respectively, and major bleeding in 0% and 1.4% (P=0.03).

Prior to this study, providers had limited data on the risks and benefits of stopping anticoagulation after ablation. The criteria used in the study for documenting no AF recurrence (at least two sessions of 24- to 72-hour Holter monitoring without atrial arrhythmia) serve as a starting point for selecting patients for anticoagulant discontinuation. Most patients in the study had paroxysmal AF (68%), which is more responsive to ablation. Although the study did not find differences in outcomes for patients with persistent AF, this subgroup was underrepresented.

CLINICAL CHALLENGE

A 45-year-old female comes to see you for her annual physical. She reports having gastric bypass surgery three years ago and says she followed up with her surgeon once and never went back. She asks you to order her routine lab work.

Given her history of gastric bypass, what lab work is recommended? Are any other studies indicated? Find out at the link below.