Digest 67: Cash Transfers, Combo Puffers, and Cagrilintide Concoctions

July 25, 2025 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this issue, we discuss cash transfers, combo puffers, and cagrilintide concoctions and more! Your Summer Med Menu Awaits! Effortlessly absorb important medical news, with our twice monthly newsletter featuring easily digestible analysis of the latest practice-changing articles, and of course…bad puns. 

Yummy! 

If you or a friend are hungry for more, sign up here.

Menu 

Issue 67

07/25/2025

Appetizers (to whet your appetite) 

Palate Cleanser (aka the melon part of the meal) 

The Main Course

A Digestif or two

Appetizers

Brought to you hot off the stove, from a variety of specialties. Delivered in super tasty, bite-sized morsels. 
-Jennifer DeSalvo MD, Joshua Gilman MD, Alyssa Mancini MD 

• Steroids to the Rescue? NEJM recently published the results of a virtual, decentralized, phase 3b, double-blind, event-driven trial of individuals with uncontrolled mild asthma despite treatment to test whether combination albuterol/budesonide therapy could decrease the risk of severe asthma exacerbation compared to albuterol alone. 2516 participants who were 12 years or older (97% were >18) were randomized to a fixed-dose combination of albuterol/budesonide (180/160 µg) or albuterol (180 µg) as-needed for up to 52 weeks. 71.4% of participants completed the trial, which was stopped early for efficacy. A severe exacerbation occurred in 5% of participants in the combination arm and 9% of those receiving albuterol alone (HR 0.53, 95% CI 0.39 to 0.73, p<0.001) in the on-treatment efficacy population (with similar results in intention-to-treat). The annualized rate of severe exacerbations was lower with albuterol-budesonide (0.15) than with albuterol alone (0.32), as was the mean annualized total dose of systemic glucocorticoids (23 mg per year with combination vs. 62 mg per year with albuterol alone). Adverse events were similar in both groups. (AM) 
• Haloperidol and QT prolongation: Myth or Reality? Haloperidol, which has long carried a safety alert for QT interval-prolongation, did not increase the rate of major adverse cardiac events (MACE) in a recent systematic review with meta-analysis published in PLoS One. This study included 84 RCTs of adult patients (n=12,180) exposed to haloperidol, and looked specifically at MACE – a composite of death, non-fatal cardiac arrest, ventricular tachyarrhythmia including torsades de pointes, and seizures or syncope. 24% of trials had a reported mean/median patient age > 65, and median follow up was 28.0 days (read: relatively short). 1144 MACE events occurred, of which 97.8% were deaths, 22 were ventricular arrhythmias, and 3 were seizures or syncope. There was no difference in MACE with exposure to haloperidol compared with placebo, and IV haloperidol was not associated with increased risk of mortality (risk ratio 0.88, 95% CI 0.72-1.08). (AM) 
• Weight loss for AFib? The PRAGUE-25 trial was a randomized non-inferiority trial recently published in JACC comparing the effects of weight loss versus catheter ablation on improving freedom from atrial fibrillation (AF) in obese patients. 203 patients with paroxysmal/persistent AF and a body mass index of 30-40 kg/m² were randomized to catheter ablation (CA) or a weight loss & lifestyle modification program plus antiarrhythmic therapy (LFM+AAD).  Seven-day holter monitor recordings were performed every 3 months. Lifestyle modification included meetings with dietitians, physical therapists, and telephone consultations where patients were encouraged to track calories, reduce alcohol consumption and increase exercise.  At 1-year follow up, 73% of patients were free of AF (the primary outcome) in the ablation group vs. 34.6% in the LFM+AAD group, which did not meet non-inferiority criteria for LFM+AAD (p = 0.99 for non-inferiority, p < 0.01 for superiority of ablation). The LFM+AAD group did achieve more weight loss (~7kg vs <1kg with CA) and A1c reduction, with a similar improvement in quality of life scores across groups. Notably, in the LFM+AAD arm, only 14.6% of patients were prescribed GLP1 agonists. (JG) 
• Combined Meds to Increase Weight Loss. Two recent phase 3a, randomized double-blind placebo-controlled trials published in NEJM evaluated the weight loss effect of the once weekly injectable Amylin analog-GLP1 agonist combination, Cagrilintide-Semaglutide, in overweight and obese patients with or without Type 2 Diabetes Mellitus (DM). The REDEFINE 1 trial randomized patients without DM to the combo drug, semaglutide monotherapy, cagrilintide monotherapy or placebo. REDEFINE 2 randomized patients with DM to the combo drug or placebo. Both studies used co-primary endpoints of change in body weight and body weight reduction >5% at week 68. The trials included 3,417 and 1,206 patients, respectively, and both showed a significant reduction in weight favoring combination therapy (-20.4% body weight change vs -3% in REDEFINE 1, and -13.7% versus -3.4% in REDEFINE 2).  In REDEFINE 1, combo therapy led to significantly more weight loss than monotherapy with either (-14.9% with semaglutide, -11.5% with cagrilintide). Combination therapy also reduced A1c in a majority of individuals in the treatment arm in REDEFINE 2 (74% vs 16% with placebo).  Side effects were common in all arms (most commonly GI). (JG) 
• Early Onset GI Cancers–Updated Guidance. A recent review in JAMA covering early-onset gastrointestinal (GI) cancers (in individuals <50 years old) noted the need for improved prevention and early detection methods. Colorectal cancer (CRC) was the most common worldwide and in the US.  Risk factors (RFs) for early-onset GI cancers are divided into modifiable RFs, including obesity, poor diet, sedentary lifestyle, cigarette smoking, and alcohol, and non-modifiable, such as family history, hereditary syndromes (e.g., Lynch syndrome), and inflammatory bowel disease. Screening is currently recommended for CRC at age 45 years for average-risk individuals, with earlier screening for high-risk individuals (e.g., those with Lynch syndrome, a first-degree relative with CRC, or advanced adenomas). Screening for pancreas cancer and esophagogastric cancer is also recommended in high-risk individuals (e.g. those with inherited genetic syndromes, 1st degree relatives with pancreatic or esophagogastric cancer, or other risk factors), with screening age determined by risk profile. For patients diagnosed with early onset GI cancers, genetic testing for germline and somatic mutations is recommended. Treatment for early-onset disease is similar to treatment for later-onset disease, with prognosis similar to or worse than for those with later-onset GI cancers. (JD) 

Palate Cleanser

The melon part. To get rid of the taste of those pesky apps.  And to fill your brain with some fun facts.

In an era where vaccines spark political debates faster than immune responses, it can be easy to lose sight of the individual patients they benefit.  In “The second life of Jacqui B,” recently published in NEJM, we meet Jacqui, a 52-year-old woman who suffered decades of complications from her congenital heart disease before receiving a life-changing heart transplant – only to live in fear of catching COVID-19 during the pandemic. As an immunosuppressed patient, Jacqui required multiple vaccine doses to safely reenter the world, and even then bore a continued risk of infection because of the medications she had to take. This led her to cautious acts of self-preservation – wearing a mask, and limiting exposure. These acts have been challenged by many around her rather than seen as a sign of respect to her organ donor and responsibility to others similar to her. “The world [now] feels smaller, and much more lonely” to Jackie. The article finishes with a reflection from Jackie: “’I don’t expect the world to revolve around me… I just hope it doesn’t forget that I’m just as much a part of it as everyone else.’”

– Jennifer DeSalvo MD

The Main Course

Alexander Chaitoff MD, MPH

A broad view of healthcare
Doctors sometimes get accused of relying too heavily on medications to treat and prevent disease. But it’s not all we do. There has been a growing movement to have doctors play a more active role in addressing the social determinants of health–e.g. by referring patients to innovative social programs or even prescribing food as medicine– in an effort to treat the underlying sociocultural factors that cause disease in the first place. 

In line with this effort, there has been growing interest in how unconditional cash transfers (from governments or nonprofits, not doctors, to patients) affect health. Unconditional cash transfers refer to giving money to individuals without limitation or direction as to what they should spend it on. This is distinct from other kinds of financial incentives, such as paying people each time they exercise or tying physician pay with certain quality metrics, which have also been widely studied. The idea behind these cash transfers is that financial hardship causes poor health, and people know best how to tackle their own financial hardships. So if you give individuals money directly (and without directives about how it should be spent), they’ll handle their situation more efficiently than a typical social program.

But do cash transfers with no strings attached improve health outcomes?

All about the money money money
There have been several recent high-profile publications that assess the impact of unconditional cash transfers on health outcomes. Most recently, a systematic review published in Annals of Internal Medicine assessed how cash transfers affect postpartum outcomes. A systematic review uses a rigorous protocol to search through and appraise all the existing literature on a given topic. Unlike a narrative review, which is a flexible summary of existing literature that relies heavily on the authors’ viewpoint, a systematic review should be objective and its conclusions replicable by other research groups. The protocols for search terms used, the extracted information from each study, and the methods to assess bias are all reported in databases like PROSPERO. Some systematic reviews also include meta-analyses, which involve using statistical techniques to combine data from multiple studies and perform analyses resulting in one quantitative summary statistic. 

In the Annals study, the authors searched for studies looking at the effect of unconditional cash transfers (UCTs) on postpartum outcomes, defined as any health-related outcome (e.g., maternal anxiety, breastfeeding, etc) within 2 years of birth. After initially identifying 6439 unique manuscripts, only 11 reports were considered primary research and included (comprising 4 quasi-experimental studies and 7 analyses from 2 randomized control trials (RCTs)). Note, some might argue that including any study type other than an RCT is a limitation, because even quasi-experiments are still at risk of bias (as we’ve discussed in past Digests). The authors concluded the studies on this topic could only be analyzed qualitatively. That is, the direction and magnitudes of effect were described for each study, with qualitative statements about the totality of the evidence, but no meta-analysis could be performed due to study heterogeneity.  In other words, there were significant differences in the populations included, the mechanism and timing of cash transfers, and the ways outcomes were measured across studies. For example, it’s tough to give one number that combines the results from a quasi-experimental study conducted in Alaska that assessed breastfeeding outcomes with a randomized trial conducted in Massachusetts that assessed skin-to-skin contact time. With this notable limitation, the authors ultimately concluded that UCTs may increase breastfeeding, but found limited evidence that they affect other outcomes (e.g. postpartum mood, substance use, etc). However, this is ultimately a narrative synthesis. While the breastfeeding conclusion was based on 4 studies, these studies all had different outcomes, and one of the two RCTs did not demonstrate increases in breastfeeding initiation or continuation, but did find an increase in the “number of mothers who met their intention to breastfeed.” 

This latest study is another relatively lackluster one supporting cash transfers. Previously, a randomized trial of 2880 low-income residents in one city in Massachusetts randomized people to receive UCTs or not and found those who received $400 per month for 9 months utilized emergency healthcare less than those who did not receive the cash transfers. However, this was conducted in one city during COVID (November 2020-August 2021), and there was no effect on health measures such as blood pressure or cholesterol levels or body weight. A separate randomized trial conducted among 3,000 low-income adults in the United States and published around the same time found that giving people $1,000 per month for 3 years similarly did not have lasting impacts on physical health, though may have increased use of office-based healthcare.

Can dollars make sense when it comes to health?
Studying cash transfers is difficult. It is difficult to fund, there are potential ethical issues to randomizing some people to get money, and it’s hard to be blinded when you know your bank account balance has just increased–to name just a few challenges. So what can we take away from the existing research on cash transfers? Currently, we don’t have evidence to guarantee health outcome return on cash transfers. There are, of course, other reasons to justify cash transfers (that may or may not have an indirect effect on health), including improving housing or food security.  But while they probably don’t hurt health–and while they certainly increase financial freedom for those receiving them–we really don’t know yet if they are buying better health outcomes. Fortunately, new programs, such as RxKids, are still experimenting with providing certain groups, such as pregnant women, cash transfers.  When the dust settles, we may find that direct cash transfers help people with certain conditions–but figuring out exactly who those people are (and the timing and duration of these transfers) will be the subject of much scientific and policy debate. Unlike Medicaid expansion, which we have seen improves health outcomes, tuck this one away as a health policy intervention still in the figuring-it-out phase. 

Read The Study Here!

Digestifs

Before you go….
we’ve got a few nibbles!

Consolidate your learning with a Quiz!  

This week on The Curbsiders: Episode #492 covers all the pearls you could ever need on hair and nails, with expert Dr. Helena Pasieka. 

Comments for the Chef

We want to hear from you!

Please share your feedback and ideas in this Survey!

Thanks so much for joining us this week.

Until next time, keep that brain hole digesting! 

The Curbsiders Digest

Issue 67

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

Jennifer DeSalvo,  Josh Gilman,  Alyssa Mancini, and Nora Taranto report no disclosures.

Alex Chaitoff reports consultancy for ALOSA health. 

Kate Grant reports no disclosures. 
 

PATREON is LIVE!

Join the Inner Circle