GLP-1 Players Seek to Differentiate in Increasingly Crowded Weight Loss Space

 

As obesity drug developers compete for the highest weight-loss efficacy, experts contend that overall health outcomes—evidenced by successful studies in therapeutic areas like cardiovascular and sleep apnea—may prove a greater market advantage.

The rise of GLP-1 receptor agonists has changed the therapeutic weight loss industry forever. Now, as more companies jostle to join the lucrative market, touting the highest percentage weight loss may take a back seat to a different competitive edge: overall health outcomes.

Certainly, the efficacy the market leaders boast has generated unprecedented demand. Eli Lilly’s Zepbound elicited up to 21% weight loss, while Novo Nordisk’s Wegovy led to around 15% weight loss in clinical studies over 72 and 68 weeks, respectively. Contenders from Novo and Amgen are similarly positioned. Novo’s CagriSema has shown between 15.7% and 22.7% weight loss at 32 and 68 weeks in Phase III trials, while last year, Amgen’s MariTide demonstrated up to 20% average weight loss at 52 weeks in Phase II studies.

“I think at the end of the day we’re going to have half a dozen or more medicines that will produce 15%–25% weight loss,” Daniel Drucker, an obesity expert at Mount Sinai’s Lunenfeld-Tanenbaum Research in Toronto said on a January call hosted by Guggenheim.

But investors don’t seem satisfied with this, given that both CagriSema’s and MariTide’s readouts have led to disappointment. For Drucker, other health benefits of GLP-1s are what make the drugs most compelling. Additionally, in a landscape where payers are increasingly reluctant to cover these expensive medications only for weight loss, outcomes studies indicating GLP-1s’ uses in other indications, such as sleep apnea, metabolic and kidney disease, reduction of heart attack and stroke risk and more, will become increasingly important, Drucker said.

“If we have all these medicines that are in that ballpark of 20% weight loss, outcomes will drive the discussion for many physicians because we do have patients who have multiple comorbidities.”

Playing the Differentiation Game

Eli Lilly’s Zepbound snagged the first ever FDA drug approval for obstructive sleep apnea in December. This followed Novo Nordisk’s label expansion for Wegovy last spring that made it the first GLP-1 approved to reduce heart health risks in adults who have cardiovascular disease and are obese or overweight.

And neither company is stopping there as they race for supremacy in the space. Both are engaged in myriad clinical trials for a handful of indications, including metabolic dysfunction-associated steatohepatitis (MASH), chronic kidney disease and even Alzheimer’s disease.

Physicians aren’t too focused on using GLP-1s to manage these comorbidities, many of which have reliable standards of care, according to a recent survey of 50 physicians. But Drucker said that while the additional approvals may not significantly expand sales of the products, they will have “a meaningful impact” on how patients and practitioners might perceive the value of a particular GLP-1 drug. Other obesity arena hopefuls seem to agree. Amgen is testing MariTide, a GLP-1 agonist/GIP receptor antagonist antibody peptide-conjugate, for various obesity-related conditions, including heart disease, heart failure, kidney disease and sleep apnea in an upcoming Phase III trial. The primary endpoint of the study, however, remains change in body weight at week 72.

Another company chasing indications outside obesity is Altimmune, which is expecting Phase IIb data in the second quarter of this year on its GLP-1/glucagon dual receptor agonist pemvidutide in MASH. The addition of glucagon drives reduction of liver fat and lipids and preservation of lean muscle mass, according to the company. Altimmune has structured its program so that each pivotal trial focuses on these outcomes in addition to weight loss.

“We are trying to treat not just obesity in general, but actually the comorbidities of obesity,” Altimmune CEO Vipin Garg said at Leerink’s Global Healthcare Conference last week. The company is preparing to forge ahead into a Phase III MASH study while actively seeking a partner for pemvidutide in obesity. By going after a more coverable disease with obesity as a comorbidity, Garg noted that there will be less pressure to lower pricing than is faced by GLP-1s currently on the market for obesity.

Oral GLP-1s Will Drive Treatment Persistence

In addition to discovering and marketing the additional therapeutic benefits of GLP-1s, the development of oral formulations may also contribute to improved overall health outcomes.

Accessibility and patient persistence remain key issues negatively affecting long-term use of approved GLP-1s, which are administered via subcutaneous injection. Just 15% of patients are still on the drugs after two years, according to a recently conducted real-world study by Prime Therapeutics—though experts expect this to rise to 25% with a “more modern product mix” led by Wegovy and Zepbound.

“It’s not about absolute weight loss; it’s about the patient experience. If they don’t stay on the drug, have we really solved the problem?” Structure Therapeutics CEO Ray Stevens asked.

Oral formulations could help solve this dilemma, Stevens told BioSpace, by increasing accessibility and tolerability by way of easier titration and dosage adjustments.

At the JP Morgan Healthcare Conference in January, Stevens polled attendees on the biggest readout of 2025. Across the entire healthcare industry, he found that, “without hesitation,” respondents said the readout of Lilly’s Phase III trial of orforglipron—the company’s oral GLP-1 contender—will be the biggest news story in 2025. The ATTAIN-2 study, which is testing the pill in patients with obesity and type 2 diabetes, is slated for completion in August.

Meanwhile, Structure is expecting a Phase II readout for its oral GLP-1 aleniglipron in the fourth quarter of this year. Capturing the full spectrum of effects the GLP-1s are providing—including reduced blood pressure, lowered lipids and improved systemic inflammation—is “really critical,” Chief Medical Officer Blai Coll told BioSpace.

“I think there’s a full plethora of effects that can be captured through these studies, and that’s what we are currently doing and planning to do,” Coll said.

Terns Pharmaceuticals is also launching a Phase II study for a weight loss pill, TERN-601, which the company touts as being “well tolerated with no treatment-related dose interruptions, reductions or discontinuations, even with rapid dose titration.” Terns is currently testing its thyroid hormone receptor beta agonist in combination with a GLP-1 in MASH.

Overall, the experts who spoke with BioSpace agreed that high efficacy levels are not the be-all-end-all in this space.

“This idea of maximum weight loss is not really the metric we should be shooting for,” contends Richard Yu, CEO of Abalone Bio, adding that by maximizing for weight loss, companies deprioritize gastrointestinal side effects, which he said are turning out to be a huge factor in patient compliance. Abalone is focused on addressing that gap with its novel approach that targets amylin, potentially alongside a GLP-1, in order to limit off-target interactions and avoid side effects.

Yu said the additional indications being studied and approved for GLP-1s in cardiovascular or inflammation-adjacent conditions are “encouraging,” adding that hitting an upstream node like obesity also results in massive downstream benefits.

But Drucker outlined the challenge such additional trials pose for a small biotech hoping to compete with approved GLP-1s in indications beyond obesity. “That’s a huge spend,” he said, adding most would likely need a well-resourced partner to do so.

In the future, Yu believes the ultimate treatment for obesity will be polypharmacological. Multiple drugs will synergize for greater tolerability with a net benefit that goes beyond weight loss effects to broader health benefits, he said. “Having different levers to pull, that’s going to be an important part of the ultimate solutions.”

https://www.biospace.com/drug-development/glp-1-players-seek-to-differentiate-in-increasingly-crowded-weight-loss-space

Alynlam’s Amvuttra Expected to Make Three in Crowded ATTR-CM Space

 

All eyes are on Alnylam as the company awaits entry into the transthyretin amyloid cardiomyopathy market, which currently includes Pfizer and BridgeBio and is projected to reach $11.2 billion by 2030.

A decade ago, transthyretin amyloid cardiomyopathy was basically a death sentence, Neil Kumar, CEO of BridgeBio, told BioSpace last year. Today, the outlook is much brighter. With effective medicines from Pfizer and BridgeBio on the market, survival rates have dramatically improved. Now, Alnylam’s vutrisiran is on the cusp of joining them.

On March 23, the FDA is widely expected to approve vutrisiran—which Alnylam markets as Amvuttra for polyneuropathy of hereditary ATTR (ATTR-PN)—for the cardiovascular manifestation of the disease. The key question for analysts—and likely Alnylam itself—is, how much of the transthyretin amyloid cardiomyopathy (ATTR-CM) market—which is projected to reach $11.2 billion by 2030—will Amvuttra be able to claim?

In ATTR-CM, the liver produces faulty transthyretin (TTR) proteins. Clumps of these misshapen proteins then build up in the heart’s main pumping chamber, leading to cardiomyopathy that makes it more difficult for the heart to pump blood to the body.

Pfizer’s tafamidis—marketed as Vyndaqel and Vyndamax—came first in this space, winning the FDA’s first approval for transthyretin amyloid cardiomyopathy (ATTR-CM) in May 2019. BridgeBio followed a little more than five years later with Attruby, which got the nod in November 2024.

Alnylam believes Amvuttra’s mechanism of action will set it apart from the competition. While tafamidis and Attruby are both transthyretin stabilizers, Alnylam’s drug is an RNAi silencer that works by knocking down both the wildtype and mutant forms of the transthyretin RNA, in turn lowering the expression of the TTR protein.

Amvuttra “works upstream of currently available therapies and, thanks to our unique technology, delivers rapid knockdown of the disease causing TTR protein, addressing the disease at its source,” Tolga Tanguler, chief commercial officer at Alnylam, told BioSpace in an email. If approved for ATTR-CM, “Amvuttra will be the first RNAi therapeutic for this indication and the only therapeutic to address both hATTR-PN and ATTR-CM.”

“We believe that the anticipated approval of Amvuttra will add another important, clinically differentiated treatment option for patients with ATTR-CM, a rare, progressive, and deadly condition,” Tanguler continued.

More Competitive Variables

The ATTR-CM space is rapidly expanding. And while BridgeBio’s launch of Attruby has “exceeded [investor] expectations,” the market expectation is that “peak sales of Amvuttra will be higher than [Attruby],” Kostas Biliouris, director of biotech equity research, BMO Capital Markets, told BioSpace. Since its November 2024 approval, more than 1,000 unique prescriptions have been written for Attruby.

Biliouris emphasized two key variables that could affect competition between Attruby and Amvuttra: administration and price. Amvuttra is administered in “only four convenient, subcutaneous doses per year,” Tanguler said, while Attruby is taken orally twice a day.

Alnylam has not yet announced a price tag for Amvuttra in the new indication, but in ATTR-PN the drug is “almost double” the price of Attruby and tafamidis, Biliouris said.

“Alnylam may or may not decide to change the price, to lower it, when they get the approval in March, but this is a very important point to consider,” he continued. Out- of -pocket costs could play a role in patient and prescriber decisions as well, Biliouris said. Because Amvuttra will be administered in a doctor’s office and is therefore part of Medicare Part B, most patients will not pay anything out of pocket, while both tafamidis and Attruby are Part D, carrying an up to $2,000 out of pocket cost per year for patients, he explained.

While Alnylam declined to comment on the potential pricing of Amvuttra in ATTR-CM, Tanguler said, “We believe that our science can only impact human health if patients have access to their medicines. . . . As such, we will measure our success by broad patient access to Amvuttra.”

Alnylam could also benefit from its experience and infrastructure in ATTR-PN, Biliouris said. In addition to Amvuttra, the company markets Onpattro for polyneuropathy caused by hereditary ATTR (hATTR). Together, the franchise brought in more than $1.2 billion in 2024, “and it’s been growing every year, which shows you they know how to do it,” Biliouris said. “They have done it before successfully.”

Alnylam is aiming for Amvuttra to be a first-line treatment choice for ATTR-CM, according to Tanguler. The data from the company’s Phase III HELIOS-B study—in which Amvuttra led to a 36% risk reduction in all-cause mortality—positions the drug for this role, he said.

The Label

While Biliouris believes Amvuttra will be approved in ATTR-CM, one factor he is watching closely is the drug’s label. Currently, the labels for tafamidis and Attruby are “pretty similar,” he said, listing improvement in cardiovascular mortality and hospitalization. Amvuttra, however, has a chance to secure the much-coveted all-cause mortality benefit, according to Biliouris.

While Attruby missed this secondary endpoint in the Phase III ATTRibute-CM trial, Amvuttra was successful in this metric in HELIOS-B, leading to a lower risk of death from any cause and recurrent cardiovascular events compared to placebo. However, Biliouris said, “this can be just incremental, and it may not have a big impact on physicians and the uptake.”

The second item Biliouris is watching for on the label is the possibility of a combination benefit with tafamidis. In HELIOS-B, “[Alnylam] saw that there is a benefit from the combination of the two drugs . . . but the improvement was not statistically significant,” he noted. Importantly, the trial was not designed to measure statistical significance on this metric.

BMO’s “bull case” is that the label will include an all-cause mortality benefit as opposed to only cardiovascular mortality and a possible mention of a combination benefit between Amvuttra and a transthyretin stabilizer, Biliouris said.

On Deck in ATTR-CM

While Alnylam is in the spotlight this week, there are more therapies waiting in the wings for ATTR-CM, including another RNA silencer being developed by AstraZeneca and Ionis. Wainua, which is approved to treat hATTR amyloidosis, is currently being studied in the Phase III CARDIO-TTRansform study for ATTR-CM, which is expected to be completed in April 2026.

Meanwhile, gene editing leader Intellia is working on what it calls a “one and done” treatment for ATTR-CM. The biotech presented Phase I data from nexiguran ziclumeran (nex-z), a gene editor, in November at the American Heart Association’s 2024 Scientific Sessions, showing “rapid, deep and durable” reductions in serum levels of TTR, according to a press release. In patients with ATTR-CM, the mean TTR reduction was 90% at 12 months.

Nex-z could have the advantage of reducing treatment burden, an Intellia spokesperson told BioSpace in an email. “Many patients experience anxiety from going to infusion centers frequently, spending time away from their families and work [to receive] repeated injections. A one-time option would eliminate that burden.” The investigational treatment could also ultimately be more effective, the spokesperson continued. “Dosing every few months produces a cyclic rise and fall of TTR levels over time, with peaks and troughs. Our data show that a one-time dose can reduce TTR to very low levels and keep it there, maintaining treatment benefit at its maximum.”

Intellia is currently enrolling the Phase III MAGNITUDE trial and is “ahead of [its] internal target projections,” according to the spokesperson. The company expects the trial to be fully enrolled by early 2027.

For its part, Alnylam isn’t stopping with Amvuttra. The company is developing a third-generation TTR-targeting RNAi therapeutic called nucresiran, which is expected to elicit deeper and faster TTR knockdown and carries the potential for biannual dosing. Alnylam reported data from a Phase I trial of nucresiran in November 2024 showing “rapid knockdown of TTR that is sustained at six months following a single dose.” A Phase III study of the candidate is expected to begin in the first half of this year, Tanguler said.

Tanguler stressed the importance of continued progress in this space, noting that ATTR-CM rates have increased approximately tenfold since 2019. Despite this, approximately 80% of patients remain undiagnosed globally, he said. “This is a large and growing category with significant unmet need.”

https://www.biospace.com/drug-development/alynlams-amvuttra-expected-to-make-three-in-crowded-attr-cm-space

China Maps Out Latest Plan To Boost Consumption, Raise Incomes: Why Prior Plans Failed

 It feels like every 3 months China comes up with another zany plan to boost the economy and kickstart consumption, which spikes stocks for a few days, but promptly goes nowhere, is quickly forgotten... only to be replaced with another zany plan 3 months later, and so on.

Today was no exception to this laughable cadence - which has achieved absolutely nothing but unleash core deflation in China for the first time since 2021 - and in a Sunday statement by Beijing State Council we learned that China will take steps to revive consumption by boosting people’s incomes, the official Xinhua News Agency reported.

Other just as vague measures include "stabilizing the stock and real estate markets, and offering incentives to raise the country’s birth rate, as the government tries to ease the deflationary pressures afflicting the economy."

Of course, we have heard all of these over and over and over, and nothing at all has changed in the past 4 years. So we kinda doubt that anyone will care this time, but we are confident that HFT and various algos who have the memory of a goldfish will push Chinese stocks higher for at least a few days before the sellers inevitably take the upper hand again.

According to Xinhua, Beijing will promote “reasonable growth” in wages and establish a sound mechanism for adjusting the minimum wage. It will also look at setting up a childcare subsidy system, as well as strengthening how investment can support consumption. 

Other highlights of the plan include:

• Enlarge variety of bond-related products suitable for individual investors
• Adopt multiple measures to promote increase in farm incomes
• Raise financial help for some students
• Appropriately increase the basic pension for retirees
• Ensure timely and full distribution of unemployment benefits
• Support tourist attractions in expanding services and the reasonable extension of business hours
• Support opening of duty-free shops in cities where conditions permit
• Boost support for trade-in programs
• Lower the interest rate on housing provident fund loans at an appropriate time
• Scale back restrictions on consumption in an orderly manner
• Accelerate the development of new technologies and products such as smart wearables and autonomous driving

More details are available here, but they may well be moot: after all, invigorating consumption has been a challenge for the government since the end of the pandemic and everything Beijing has thrown at the problem has sunk into a seemingly unquenchable deflationary vortex. Retail sales have been anemic while consumer prices fell into deflation in February for the first time in over a year, although the latest macroeconomic dump suggests that things may be turning after all key data printed just slightly better than expected:

• *CHINA JAN.-FEB. RETAIL SALES RISE 4% Y/Y; EST. 3.8%
• *CHINA JAN.-FEB. FIXED INVESTMENT RISES 4.1% Y/Y; EST. 3.2%
• *CHINA JAN.-FEB. INDUSTRIAL OUTPUT RISES 5.9% Y/Y; EST. 5.3%

At annual parliamentary meetings this month, the country’s leadership made boosting consumption their top priority for the first time since President Xi Jinping came to power over a decade ago.

Ahead of the announcement, Chinese stocks rallied the most in two months on Friday after the State Council, China’s cabinet, announced that officials from the finance ministry, the central bank and other government departments plan to hold a press conference Monday on measures to boost consumption.

In a series of posts on X, China watcher Michael Pettis shared his skeptical view on the latest events in China, explaining why so far all attempts to kickstart the economy have failed. 

He starts by observing the above - namely that the government and Communist Party issued a lengthy list of planned initiatives on Sunday to get people to spend more, including larger pensions, better medical benefits and higher wages, but they "assigned many of these tasks to the country’s local governments, many of which are struggling under enormous debts and plummeting revenues from the sale of state land."

This, according to Pettis, is the problem with every attempt to boost the consumption share of GDP.

He then notes that the sustainable way to boost consumption is to increase the share of GDP retained by households. But increasing their share requires explicit or implicit transfers from either businesses or government. If the household share rises, after all, someone else's share must decline.

And while Beijing wants local governments to absorb said transfers, given their precarious cashflow positions, for now they can do so mainly by placing new burdens on households or businesses, e.g. through taxes, layoffs, fees, or cutbacks on existing services.

As a result, the net impact on households is reduced, and the remaining costs are absorbed by businesses. The former doesn't help boost consumption, and the latter, by indirectly forcing businesses to absorb the costs, is bad for the economy.

The only other way to do so involves forcing local governments either to transfer to households a large part of the substantial assets they control, or to liquidate those assets in order directly or indirectly pay for higher household income.

The problem, according to Pettis, is that this implies a radical transformation of the relationship between Beijing and local governments and between local governments and the households and businesses in their jurisdiction, and given the sheer extent of the needed transfers, it will be very difficult.

This is why, for all the years of posturing and promising to boost consumption, it has been impossible for China to make much progress to reboot the economy. Since Beijing has to raise the household share of GDP by 10% at the very least, that means an equivalent reduction of someone else's share.

Pettis also notes that many analysts insist that China will choose to avoid rebalancing altogether, but they miss the point. These levels of imbalance simply cannot be sustained if neither China nor the rest of the world can absorb the growing gap between consumption and production.

At the end of the day, China will rebalance one way or another. The important question is how it rebalances: whether an increase in the household share of GDP will occur in the form of a debt crisis and a sharp contraction in GDP, as occurred in the US in the early 1930s... or through many years of stable consumption growth and much lower GDP growth, as occurred in Japan after 1990, or of a surge in consumption that keeps GDP growth stable (which would be historically unprecedented).

These are arithmetically the only three ways to rebalance. And since all are extremely painful, either acutely now or chronically over the long-term, no surprise then that Beijing just keeps pretending it will do something while merely kicking the can until it is finally one day forced to do something.

https://www.zerohedge.com/economics/china-maps-out-latest-plan-boost-consumption-raise-incomes-heres-why-all-such-prior-plans

Getting Out of Forever Wars

 by Don McGregor via RealClearDefense,

A Pragmatic Approach to Protecting U.S. Security Interests

Introduction

Since the 9/11 attacks, the United States has been mired in "forever wars"—prolonged conflicts with no clear victory, draining trillions of dollars, thousands of lives, and economic vitality. A 2023 Pew poll shows 54% of Americans favor reducing overseas military commitments, with 83% prioritizing domestic needs—a clear call for change.

The U.S. can no longer afford years of military overreach. A pragmatic strategy emphasizing diplomacy, allied burden-sharing, and strategic restraint is essential to protect national interests without exhausting finite resources.

The Overwhelming Cost of War

The post-9/11 wars have exacted a staggering toll. Brown University’s Costs of War Project estimates the U.S. has spent $8 trillion—38% of 2020’s GDP—on conflicts in Iraq, Afghanistan, Pakistan, and Syria, equating to $24,000 per citizen.

Future interest on this debt could add $2.2 trillion to the national debt by 2050, burdening future generations. Human losses are equally dire: 7,000 service members and 8,000 contractors killed, 55,000 injured, and 940,000 total deaths from direct violence, with 3.6 million more dying indirectly in war zones.

Beyond numbers, the mental health crisis is profound. Veterans and active-duty personnel from these conflicts have died by suicide at four times the rate of combat losses—over 28,000 since 2001, according to 2022 VA data – mainly driven by post-traumatic stress disorder and repeated deployments.

Adding to the exhausting cost of conflict, caring for these veterans will cost $2.2-$2.5 trillion by 2050. These financial and human costs prove the wars’ unsustainability; constrained resources and public concerns require the U.S. to reassess its global security approach.

Rethinking Overseas Commitments

The U.S. maintains 750 military facilities across 80 countries, per a 2021 International Institute of Strategic Studies, at an annual cost of $80 billion—$55 billion for bases alone. The Quincy Institute reports that 91% of post-9/11 operations relied on these bases. Yet, they’ve often fueled instability—think of the disorder stemming from Iraq’s insurgency or Afghanistan’s collapse—rather than the security they were supposed to provide. This sprawling footprint, born of Cold War logic, no longer aligns with today’s fiscal environment, demanding a leaner, more practical approach.

A Pragmatic Path Forward

Some argue that overseas military bases help deter terrorism, but the evidence suggests otherwise. According to the Cato Institute (2023), the probability of dying in a U.S. terrorist attack is just 1 in 150 million.

Since 9/11, America has experienced nine terrorist attacks, resulting in a total of 44 deaths. In contrast, during the same period, the U.S. military suffered over 7,000 fatalities and 55,000 injuries in Iraq and Afghanistan, raising questions about the purpose of military operations overseas.

The cost alone is staggering. According to a Cato Institute report, a conservative baseline for total overseas basing costs is $80 billion annually, with some estimates reaching $100-$150 billion. This reflects differing indirect expenses, like troop support, highlighting the obscurity of overseas spending.

A 2023 RAND study also found that 30% of bases lack strategic purpose. A 25% reduction, focusing on outdated Cold War sites and unproductive Middle East efforts, would save $15 billion annually.

However, completely withdrawing is unwise; bases in Japan and Germany still deter Russia and China and allow forces to posture when needed. Closing outdated posts in stable regions—like parts of Europe or Asia—frees billions for pressing domestic defense needs.

The use of hard power has become overextended, yielding little success and eventually weighing heavily on the American public. A more effective strategy entails carefully reducing America’s overseas presence, reallocating resources, and reprioritizing homeland defense.

Strengthening Homeland Defense

President Trump’s campaign emphasized ending long-term military engagements, reducing overseas commitments, and reprioritizing defense strategies to enhance defending the homeland.

His 2025 executive order for an “Iron Dome” system reflects this shift, focusing on missile defense against nuclear and newer hypersonic weaponry from advancing adversaries. However, these initiatives currently face funding challenges.

The FY2024 defense budget ($850 billion) allocates $69 billion to overseas operations—defending allies—while just $29.8 billion (3.5%) boosts missile defense, unchanged since 2019.

Redirecting even half of that $69 billion could modernize defenses, aligning spending with existential risks over foreign entanglements.

However, missile defense is not the only way to protect the nation. It also demands attention to vulnerabilities closer to home, such as securing the borders—another pillar of homeland security.

Securing the Border

Border security, a neglected homeland priority, ties directly to resource reallocation. In FY2024, Customs and Border Protection (CBP) logged 3 million encounters at the southern border—up 400% from the 700,000 in the 2020s—costing an estimated $130 billion, challenging public safety and straining national security.

To help tackle this unprecedented challenge, President Trump's recent executive orders, which declare a national emergency at the southern border and direct the military to support the Department of Homeland Security (DHS) in safeguarding the nation's territorial integrity, highlight the priority of protecting the homeland.

DHS has also ramped up the activities of Immigration and Customs Enforcement (ICE), leading to a significant 627% increase in the detainment of criminal aliens since January. This surge has prompted DHS to request additional military assistance to aid the detainment process. As a result, more military troops are being deployed to support CBP along the border, and the military detention facility at Guantanamo Bay is being repurposed to accommodate the detention of criminal migrants.

While reallocating military resources from overseas commitments to border security can effectively address domestic threats without requiring additional spending, as illustrated by Secretary of Defense Hegseth's recent decision to shift eight percent of the FY26 defense budget toward homeland priorities, this approach also highlights a more significant imbalance in U.S. defense spending.

Burden Sharing Security

Disproportionate global security commitments add to the problem, as the U.S. must push NATO allies to meet their 2% GDP defense spending target—America spent twice their combined total from 2014 to 2022.

Leading allies, like the United Kingdom and Germany, spend less as a share of Gross Domestic Product (GDP), with the U.S. shouldering a disproportionate burden of European defense. Additionally, the U.S. upholds numerous other global security agreements that extend well beyond Europe, such as the Pacific Deterrence Initiative—a U.S.-only defense investment and activity used to counter China that costs $10B annually.

The United States can no longer bear the burden of defending others. It must reassess its global security stance and agreements to ensure that costs are shared equitably. A balanced use of projecting power is needed to secure American influence abroad.

Balancing Power Projection

America’s decades-old philosophy of fighting its battles on someone else’s property remains vital to national security. A platform that can project US power quickly and support those efforts remains relevant.

Overseas “power projection platforms”—like overseas mobility bases and carriers in the Pacific—are necessary, enabling rapid response and sustainment to a crisis. However, basing that does not support projecting power should be reconsidered for closure. Trimming these frees funds for soft power—diplomacy and economic leverage—that achieves similar ends at a lower cost.

Harnessing Soft Power

Soft power—persuading through attraction, not force—offers a sustainable edge. Diplomacy can preempt conflicts that mimic hard power wins, such as the ceasefire that paused fighting in Sudan, allowing 150,000 to flee safely and aid to reach 500,000, per UNHCR reports.

Diplomacy can also secure trade deals, such as the 2020 U.S.-Japan Trade Agreement, which cut tariffs and secured U.S. farm exports to counter China’s trade dominance. Yet, while diplomacy can secure trade wins to help balance its trade, its effectiveness diminishes when multilateral agreements lead to persistent inequities.

For example, the Asian-Pacific Economic Cooperation (APEC), a multilateral trade agreement, incurred a deficit of $913 billion in 2024, a 12 percent increase ($97.7 billion) over 2023. Further, according to the Bureau of Economic Analysis, America’s total global goods and services deficit was $918.4 billion in 2024, up $133.5 billion from $784.9 billion in 2023.

This unsustainable trend indicates that the U.S. needs to rethink its negotiating approach in line with more equitable agreements that work directly with each partner, making adherence and fairness more manageable.

However, diplomacy and trade agreements alone cannot guarantee a nation's security. Economic strength is vitally important and underwrites all its activities, making it essential to influence, leverage, and safeguard its interests.

Prioritizing Economic Security

The U.S. economy—$29 trillion in 2024, 25% of global wealth—thrives on energy, innovation, and resilience. For example, since 2019, an 8-quadrillion-BTU energy surplus has fueled energy exports, supporting Europe against Russia and countering Iran. Energy independence and growth are critical in maintaining America’s edge over rivals and securing its position as a preeminent global power.

However, the U.S. must address significant financial challenges, including its $34 trillion national debt and nearly $2 trillion budget deficit. While the U.S. currently has an economic advantage over China, purchasing power parity, or how much your currency can buy, shows that China leads by 23% and is growing. More concerning is that experts predict that China will surpass the total U.S. economy by 2040.

Remaining a global leader requires economic security and realigning priorities. Protecting against rising financial challenges and economic juggernauts like China means redirecting excessive global commitments to infrastructure and tech, not unproductive overseas commitments.

Conclusion

The post-9/11 wars have cost the United States $8 trillion, nearly a million lives directly and indirectly, and decades of overstretched resources—losses no nation can sustain indefinitely. To secure its interests, the U.S. must pivot from endless military entanglements to a strategy of calculated restraint: reducing outdated overseas commitments, redirecting funds to homeland defense and economic resilience, and leaning on diplomacy and allied cooperation to project influence.

This shift isn’t retreat—it’s recalibration. By prioritizing what strengthens the nation, from border security to soft power, America can safeguard its future without repeating its past mistakes.

Major General Don McGregor (USAF, ret.) is a combat veteran and an F-16 fighter pilot. While serving as a General Officer in the Pentagon, he was the National Guard Director of Strategy, Policy, Plans, and International Affairs, advising a four-star Joint Chiefs of Staff member.

https://www.zerohedge.com/political/getting-out-forever-wars

Russia demands 'ironclad' guarantees in peace treaty with Ukraine

 

Russia seeks firm guarantees in any Ukraine peace deal, demanding Ukraine's neutrality and exclusion from NATO. The U.S. pushes for a ceasefire, with Moscow stressing its stance against NATO observers. Discussions focus on security guarantees and peace-keeping deployments, with European allies showing openness towards peacekeeping forces.

In a critical move towards resolving the ongoing conflict in Ukraine, Russia is stressing the necessity of obtaining 'ironclad' guarantees that Ukraine remains neutral and excluded from NATO, as per Deputy Foreign Minister Alexander Grushko's statement published on Monday. The country remains steadfast in its position, amid U.S. President Donald Trump's efforts to gain Russian President Vladimir Putin's support for a 30-day ceasefire proposal, which Ukraine accepted last week.

As discussions intensify, Trump's anticipated dialogue with Putin is aimed at exploring diplomatic avenues to end the three-year war. U.S. envoy Steve Witkoff, after a positive meeting with Putin in Moscow, disclosed to CNN that these talks are crucial. Meanwhile, in an interview with Russian media outlet Izvestia, Grushko emphasized that Russian demands form a crucial condition for any sustainable peace treaty.

Moscow's firm disagreement with NATO's presence in Ukraine is clear, with Grushko reiterating that any deployment, under any label, would complicate the region's security dynamics. Although European nations and Australia show readiness to send peacekeeping troops, the contention persists, particularly regarding NATO's involvement.

https://www.devdiscourse.com/article/politics/3309874-ironclad-guarantees-russias-demands-in-ukraine-peace-deal

David Sacks Exposes The Real Reason Behind DOGE Derangement Syndrome

 During President Donald Trump’s recent joint address to Congress, viewers likely noticed several Democrat lawmakers brandishing signs reading "MUSK STEALS." 

Now, we've got nationwide attacks on Tesla dealers.

A member of the Seattle Fire Department inspects a burned Tesla Cybertruck at a Tesla lot in Seattle, Monday, March 10, 2025. (AP Photo/Lindsey Wasson)

AI & Crypto Czar David Sacks says that this immature display, widely derided by conservatives, provides a revealing glimpse into the Left’s underlying mindset - exposing their belief that they alone should control American taxpayer funds, in opposition to the Trump administration’s clear mandate to eliminate financial waste and abuse across the federal government.

"I was at the State of the Union and up in the balcony. I was looking down at the Democrats holding up these silly little signs and the sign that I saw the most was one that said ‘Musk Steals,’” Sacks began in his Saturday evening interview with Fox News’s Lara Trump. “I really thought about that. 

How is Elon stealing? He’s returning money to the Treasury. Then it hit me, they actually have come to believe that this taxpayer money is theirs and by returning it to the Treasury, Elon is stealing from them. That’s my best explanation of why they’re in such hysterical state about this.”

Sacks concluded that Democrats are enraged because Trump, with the support of the Department of Government Efficiency (DOGE), is finally delivering on his central campaign promise to drain the swamp.

“But of course, Elon isn’t stealing anything. He is making sure that the federal government is taking good care of our money and that we’re not wasting it, it’s not going to corruption or fraud, and I think that just has the swamp in an absolute tizzy because he, along with president, and at the president's direction, they are draining the swamp."

The Democrats’ opposition to DOGE has grown louder in recent weeks as federal agencies have continued to cuts thousands of jobs and slash tens of billions of dollars in wasteful spending. On Friday, Sen. Chris Van Hollen (D-MD) proposed Senate Amendment 1272 to H.R. 1968, amending a bill to "prohibit the use of appropriated funds by DOGE," but the amendment failed, 52-48. Sen. Lisa Murkowski (R-AK), a critic of DOGE, was the sole Republican to vote for the measure.

Sen.Joni Ernst (R-IA), who leads the Senate’d DOGE caucus, highlighted this week that DOGE has saved taxpayers $115 billion, amounting to $714 per taxpayer.

“Some of DOGE’s findings include: The Small Business Administration gave out more than $300 million in loans to thousands of children 11 years old and younger,” the senator pointed out.

“Thanks to DOGE, that contract was canceled, now the plants will be watered for free.While DOGE keeps delivering more savings every day, Democrats are more upset by the effort to stop wasteful spending than by the misuse of tax dollars," she added. 

https://www.zerohedge.com/political/david-sacks-exposes-real-reason-behind-doge-derangement-syndrome

Zydus Lifesciences Gets US FDA Final Nod for Eluxadoline Tablets

Zydus Lifesciences has received final approval from the US Food and Drug Administration (USFDA) to manufacture Eluxadoline Tablets, 75 mg and 100 mg. Eluxadoline is a mu-opioid receptor agonist, indicated in adults for the treatment of irritable bowel syndrome with diarrhoea.

https://www.cnbctv18.com/market/zydus-life-share-price-receives-final-approval-from-usfda-for-eluxadoline-tablets-19573999.htm