Business
Japanese Ketoacidosis Cases After Tirzepatide Use Spark Call for Safer Weight Loss Beyond Off-Label Rules
TOKYO — Japanese physicians say the debate over popular weight-loss injections has been aimed at the wrong target. Stopping off-label prescriptions and black-market sales is necessary, they argue, but it will not prevent the most serious harm if people keep starving themselves while the drugs suppress appetite.
In an editorial published Aug. 26 in Diabetology International, researchers led by Wataru Ogawa of Kobe University wrote that “inappropriate use” of GLP-1 and dual GIP/GLP-1 medicines should be judged on two tracks at once: whether the drug was obtained legally, and whether the weight loss itself was medically safe.
“We argue that inappropriate use should be understood from two complementary perspectives: regulatory appropriateness and medical appropriateness,” they wrote. Medical appropriateness, they added, “encompasses not only drug-related risks but also the safety of weight reduction itself.”
The warning follows a cluster of Japanese hospital reports in which young women without type 2 diabetes developed ketosis or ketoacidosis after using tirzepatide, the active ingredient in Mounjaro and Zepbound. The three patients cited in the editorial were 21, 21 and 23 years old. Two were not obese when they started the drug. The third began treatment with a body mass index of 30.2 and had already fallen to 21.9 by the time she was hospitalized. None of the reports documented nutritional counseling or ongoing medical supervision.
Two of the women were on the lowest weekly dose, 2.5 milligrams. The third had moved up to 5 milligrams after four weeks at the starting dose. One case involved deliberate carbohydrate restriction. In all three, the authors said, “inappropriate dietary restriction during weight-loss attempts may also have contributed.”
The distinction matters because GLP-1-based drugs are already known for nausea, vomiting, diarrhea and constipation. Those gastrointestinal effects can quickly cut food intake. Combined with a crash diet, the result can be starvation metabolism: the body burns fat so fast that ketone acids accumulate in the blood. That pathway is different from classic diabetic ketoacidosis, and it can appear even when blood sugar is normal or only mildly high.
Published case reports fill in the clinical picture the editorial summarized. In one, a 21-year-old Japanese woman with obesity started weekly 2.5-milligram tirzepatide while restricting carbohydrates, lost 21 kilograms in a month, then arrived in an emergency department with hypoglycemia and severe metabolic acidosis after persistent vomiting. Intravenous glucose corrected the acidosis within 12 hours; she did not need insulin. In another, a 23-year-old woman who was not obese obtained 2.5-milligram tirzepatide from an aesthetic clinic, gave herself a second dose, and developed nausea, vomiting and diarrhea. Tests showed high-anion-gap acidosis and sharply elevated ketone bodies. A third report described a 21-year-old who bought tirzepatide through an online service, dropped from 47 kilograms to 41 kilograms, and was later found to have anorexia nervosa after presenting with starvation ketosis.
Ogawa and colleagues said those events should not be dismissed as rare quirks of one molecule. Tirzepatide and related drugs cause weight loss mainly by reducing appetite. That happens whether the prescription is on-label for obesity or type 2 diabetes, off-label for cosmetic slimming, or obtained through an unofficial channel. The authors wrote that many of the worst metabolic complications “may reflect unsafe weight-loss practices rather than the intrinsic pharmacological toxicity of the drug,” while adding that drug toxicity remains a separate concern.
Japan’s reimbursement rules help explain why diversion has become a political issue. Wegovy, a semaglutide product approved for obesity, and Zepbound, tirzepatide approved for obesity, are covered only at specialized institutions and only after a structured six-month lifestyle program. Mounjaro contains the same tirzepatide molecule but is reimbursed for type 2 diabetes without those obesity-program gates. Japanese media have reported illegal resale of insured Mounjaro to people seeking cosmetic weight loss. The Health Ministry issued a notice in mid-June on improper off-label use of GLP-1 drugs for dieting and has said it is weighing tighter guidance with the bureau that oversees medical practice.
The editorial’s larger claim is that a compliance crackdown will not be enough. “Current efforts to promote the appropriate use of GLP-1-based medications have largely focused on regulatory compliance related to off-label prescribing and illegal acquisition,” the authors wrote. Messages that simply tell people not to use the drugs off-label, they said, “are unlikely to curb inappropriate use.”
What they want instead is a shift in how success is defined. “We propose that the discussion surrounding GLP-1-based therapies should move beyond appropriate drug use toward appropriate weight reduction,” they wrote, “regardless of whether weight loss is pursued to improve obesity-related health conditions or for cosmetic purposes.”
That standard includes realistic targets, enough protein and calories to avoid undernutrition, and monitoring for the point at which further loss becomes harmful. The authors pointed to a recently proposed idea they call female underweight/undernutrition syndrome, a framework for the physical and psychological damage that can follow when women are driven below a healthy weight. Underweight, they noted, is itself a clinical problem, not a cosmetic victory.
The argument lands in a global market that has already outrun clinic capacity. GLP-1 and dual agonists have changed obesity care by producing large average weight losses and improvements in blood pressure, lipids and diabetes control. Demand has also produced compounded products, online questionnaires with little follow-up, social-media marketing aimed at people who do not meet obesity criteria, and a secondary trade in leftover pens.
International agencies have begun to describe the same pattern. In a July 30 statement, World Health Organization advisory committees said they were concerned about people obtaining GLP-1 medicines “outside approved indications and medical settings, including through online platforms,” especially those without obesity and without a prescription from a qualified clinician. The committees urged patients to use only authorized sources and to stay under medical follow-up. WHO’s own guidance on the drugs for adult obesity remains conditional and pairs medication with behavioral care.
Other research published this year has widened the safety file beyond Japan. An interim U.S. survey in JAMA Psychiatry found that among more than 400 people with eating disorders, about one in three reported having used a GLP-1 drug and about one in 10 reported misuse. A consensus statement from European obesity and dietetic groups warned that rapid loss, appetite collapse and gastrointestinal side effects can create nutritional and psychological risk even in supervised treatment. U.S. poison-center analyses have shown a sharp rise in calls after semaglutide’s weight-management approval, many of them dosing errors rather than intentional overdose.
None of that erases the drugs’ documented benefits when they are used as intended. It does change the question clinicians are being asked to answer. The Japanese editorial treats “How did you get the pen?” as incomplete. The better questions, the authors say, are how fast the weight is coming off, what the person is still eating, and whether anyone is watching for starvation chemistry.
“Whether pharmacological therapy is administered or not, weight reduction should be supported by appropriate nutritional counseling, careful monitoring, and ongoing medical supervision,” they wrote. In the end, they said, success “should be judged not only by the amount of weight lost, but by how safely and appropriately such loss is achieved.”
Business
Watch: How much can Canada fight back in its trade war with the US?
The US may be the bigger trading partner, but Canada shouldn’t be counted out quite yet in the escalating trade war between the two countries.
It is the top customer for 26 US states, including Maine, Michigan, and Wisconsin, as well as being in the top three for 45 of the 50 American states – suggesting Prime Minister Mark Carney has room to manoeuvre in a trade fight.
BBC’s Jessica Murphy explains how Canada has more leverage than it may seem in the spiralling dispute.
Read the latest on the escalating tariff fight here.
Video by Eloise Alanna.
Business
Volkswagen AG (VWA:CA) Shareholder/Analyst Call – Slideshow
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Business
Jobs Growth Update: Modest Improvement In August
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Business
Docusign Raises Sales View on Higher Second-Quarter Revenue
Docusign DOCU 3.70%increase; up pointing triangle raised its sales outlook for the second time this year, citing a boost from artificial intelligence-related demand.
The digital document-signing platform said Thursday it now expects annual revenue to be $3.50 billion to $3.51 billion, up from its previous guidance of $3.49 billion to $3.50 billion.
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Business
Definium Therapeutics CEO Robert Barrow sells $721,732 in shares

Definium Therapeutics CEO Robert Barrow sells $721,732 in shares
Business
Inturai Ventures closes private placement raising $963,714

Inturai Ventures closes private placement raising $963,714
Business
Crude Futures End Mixed With No End in Sight to U.S.-Iran Conflict
1504 ET – Oil futures end the session little changed as the market sees the U.S.-Iran conflict going on for longer with this week’s resumption of military strikes. “Iran is trying to constrain the Strait of Hormuz, and the U.S. is trying to open it,” says Simon Wong, portfolio manager at Gabelli Funds. “There’s a dispute about how much oil is coming out, but I don’t think Iran wants to let that card go because that’s all the leverage they have at this point.” WTI for October delivery rises 0.3%, to $91.30 a barrel, in a fourth consecutive gain. Front-month Brent for November delivery slips 0.1%, to $95.52 a barrel, snapping a three-session winning streak. (anthony.harrup@wsj.com)
Oil Extends Rally With Iran Conflict Seen Dragging On
0855 ET – The rise in oil prices stretches into a fourth day with the resumption of fighting in the Middle East rekindling concerns about tight global supplies for longer. “Some measure of comfort had gradually been developing as increased ships were reportedly exiting the Strait of Hormuz,” Ritterbusch & Associates says in a note. But with a diplomatic solution seen far off “it is safe to say that there is no end in sight to this quagmire that is likely to keep petroleum prices much elevated through the end of this year.” WTI is up 1.6% at $92.46 a barrel, and Brent gains 1.1% to $96.65 a barrel. (anthony.harrup@wsj.com)
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Business
Tetris says it had no role in White House ‘Build the Wall’ game

Tetris says it had no role in White House ‘Build the Wall’ game
Business
Bumper FCNR(B) inflows may dilute banks’ margins but boost earnings by up to Rs 11,000 crore: Jefferies
While fortnightly data on credit growth won’t change much as it captures domestic credit, Jefferies noted that banks’ balance sheet credit growth can improve by 3-4 ppt as it captures the leverage provided by banks from foreign branches. For the banking sector, Jefferies expects domestic credit growth to moderate from 18% now to 15% by March 2027 as base resets in December 2026 and supply from bonds and ECB normalise.
The strong FCNR(B) inflows meanwhile can lift deposit growth from 12% pre FCNR-B to 17% (currently at 15%), Jefferies said, adding that it expects slight normalisation by the end of March 2027 to 16%. Fortnightly LDR data meanwhile will likely fall from 83% pre-FCNR-B to 80% (82% now), the international brokerage said.
What happens to banks’ margins?
Net interest margins (NIM) for banks will likely fall in the second quarter due to a timing gap in the placement of banks’ fund-raising, Jefferies said in its latest report. It added that banks are likely to quantify the short-term non-recurring impact on NIMs in their earnings print for Q2. Structurally, FCNR-B is a lower NIM business due to the double-counting of deposits and assets, and the first leg makes a 10-15 bps spread, the analysts added.
While FCNR-B deposits dilute NIMs and return on assets (ROA), they are accretive to net interest income (NII) and return on equity (ROE), Jefferies said. In fact, it estimates that at the sector level, it may boost earnings by Rs10,000-11,000 crore, annually, which is 2% of PBT. “We feel it’s better to see from the lens of an incremental profit pool, instead of margins. We feel banks may be able to normalise margins over 2-4 quarters by reducing dependence on high cost wholesale deposits, reducing share G-Secs that is held towards LCR and lower share of low-margin overseas trade financing.
Also read | Explained: What $127 billion FCNR(B) inflows mean for ICICI Bank, HDFC Bank, other bank stocks
Nomura says FCNR(B) scheme gives forex firepower to RBI
Nomura in its note said that the bumper finale to the FCNR(B) scheme has given the RBI ample foreign exchange reserves firepower, adding that the challenge now is how it will mop up the surplus liquidity. It expects this to boost the balance of payments surplus to $66 billion in FY27 from a deficit of $23.6 billion in FY26.
Motilal Oswal Financial Services meanwhile said that the record high FCNR(B) inflows have backed its estimates of a 150 bps increase in system credit growth to 15.5-16% for FY27. It noted that ICICI Bank mobilised $17.9 billion, capturing 14% market share of the total FCNR(B) inflows. SBI has garnered $9 billion a few days prior to the close and is expected to beat its $10 billion guidance. RBL Bank has added $3.4 billion, capturing 2.7% share, better than its deposit market share of nearly 0.5%.
“FIIs, who were on a selling spree before the FCNR(B) deposit scheme, have added net inflows of $4.8b in the last two months, while INR depreciation against USD has also stabilized,” Motilal noted. While net interest margins are expected to be under pressure in the near term on account of limited spread on the overseas leveraged portion of FCNR(B) deposits, the deployment of these deposits and an improving asset mix will drive faster balance sheet growth and support earnings, according to the domestic brokerage.
Also read | Which stocks should you buy ahead of the festive season? Here are Kotak Securities’ top 10 picks
(Disclaimer: Recommendations, suggestions, views and opinions given by the experts are their own. These do not represent the views of The Economic Times)
Business
Spain’s Iris2 Investment Driven By Musk’s Control Of Global Satellites, Minister Says Amid Starlink Dominance
TUPPER LAKE, N.Y. — Spain’s decision to commit up to 2 billion euros toward Europe’s Iris2 satellite constellation was directly motivated by concerns over Elon Musk’s dominant position in global satellite communications, according to Spanish Science and Innovation Minister Diana Morant, who oversees the country’s space sector.
Morant said Musk’s control over roughly two-thirds of all satellites currently operating in orbit, largely through his company SpaceX’s Starlink broadband network, factored significantly into Spain’s calculus when the government finalized its major investment in Iris2, Europe’s answer to Starlink, according to reporting from Space Intel Report.
Spain formally committed to spending up to 2 billion euros, or approximately $2.3 billion, into the Iris2 multi-orbit constellation in late July, when Spanish Prime Minister Pedro Sánchez announced the investment as part of the country’s broader Multi-orbit Satcom Special Modernization Program. The funding will support a national secure satellite broadband constellation that will ultimately be integrated into the wider European Iris2 network, while remaining under direct Spanish control.
Iris2, formally known as Infrastructure for Resilience, Interconnectivity and Security by Satellite, is being jointly managed by the European Commission and the SpaceRise consortium, a group of the continent’s leading satellite fleet operators, including SES, Eutelsat and HispaSat. The project represents Europe’s most significant effort to date to build an independent, secure satellite communications capability, reducing the bloc’s reliance on commercial providers such as SpaceX’s Starlink network for critical government, defense and emergency services communications.
Spain’s commitment marks the largest single national contribution to Iris2 announced so far among European Union member states, surpassing an earlier pledge of approximately 470 million euros, or roughly $536 million, from Poland, which is funding six dedicated satellites for the constellation’s medium-Earth-orbit layer and six more for its larger low-Earth-orbit shell.
The overall Iris2 program carries a total planned cost exceeding 15.6 billion euros, or roughly $18 billion, according to figures from the European Commission and industry reporting. The funding structure combines 11.6 billion euros in public investment from the European Commission and the European Space Agency with up to 4 billion euros contributed collectively by the three SpaceRise consortium members. The full constellation is designed to include 330 new satellites in low Earth orbit alongside 12 additional satellites in medium Earth orbit, with initial services expected to begin in 2030 following the program’s first satellite launches in 2029.
Spain’s own national contribution to the broader effort will fund a sovereign satellite communications capability comprising satellites operating across both low and medium Earth orbit, according to details of the Spanish Defense Ministry’s budget disclosure accompanying the announcement. That national system is designed to remain fully compatible with the broader Iris2 architecture while staying under direct Spanish governmental control, reflecting a broader European push toward what officials have described as sovereign satellite capabilities independent of any single foreign commercial provider.
HispaSat, part of Spain’s Indra Group, has separately been selected as the prime contractor for the ground segment of the broader Iris2 program, a role valued at more than 1.6 billion euros covering antenna infrastructure, control systems and land-based network connectivity across the constellation’s various orbital layers. That selection makes Indra the first Spanish company to secure a lead contractor role within the broader European program, further underscoring Spain’s growing stake in the project beyond its direct national funding commitment.
Musk’s Starlink network has grown rapidly since its initial launches, now comprising thousands of satellites providing broadband internet service across much of the globe, including regions with limited access to traditional terrestrial internet infrastructure. That scale has made Starlink the dominant player in the emerging low-Earth-orbit satellite broadband market, a position European officials have increasingly cited as a strategic vulnerability given the network’s status as a commercial asset controlled by a single American entrepreneur rather than a sovereign or multilateral European entity.
Concerns over reliance on Starlink for critical infrastructure have intensified across Europe in recent years, particularly in the context of the ongoing war in Ukraine, where Starlink terminals have played a significant role in maintaining military and civilian communications. That dependency has fueled broader European interest in developing independent satellite communications capabilities less exposed to decisions made by a foreign commercial operator, a dynamic that has featured prominently in policy discussions surrounding Iris2’s development.
European telecommunications companies have signaled a similarly cautious stance toward relying on Iris2 itself absent competitive terms. Telecom operators Orange and Deutsche Telekom have previously indicated they would only purchase capacity on the Iris2 constellation if the network’s offerings proved competitive with existing commercial alternatives, reflecting broader industry skepticism about whether a government-backed constellation can match the cost and performance benchmarks already established by Starlink’s commercial network.
Morant’s comments came during remarks at industry gathering in Tupper Lake, New York, where Space Intel Report covers ongoing developments across the global satellite and space industry. Her characterization of Musk’s satellite dominance as a motivating factor behind Spain’s Iris2 commitment reflects a broader pattern among European officials who have increasingly framed satellite communications sovereignty as a matter of national and continental security, rather than purely a commercial or technological consideration.
Spain’s investment adds to a growing list of national contributions to Iris2 from individual European Union member states, building on the underlying public-private partnership structure established between the European Commission, the European Space Agency and the SpaceRise consortium. With initial satellite launches still several years away and full operational capability not expected until 2030, the program remains in a relatively early phase of implementation, even as individual countries including Spain and Poland continue announcing substantial national funding commitments tied to the broader constellation.
As Iris2 continues moving through its development phase, with major manufacturing and launch contracts still being finalized among consortium members and their industrial partners, European officials are likely to continue emphasizing the strategic rationale behind the program, framing it explicitly against the backdrop of Starlink’s continued global dominance in the satellite broadband sector under Musk’s ownership through SpaceX.
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