Metformin Hydrochloride

A low-cost antidepressant may offer new hope for people struggling with long COVID fatigue. In a randomized clinical trial involving 399 adults, fluvoxamine significantly reduced fatigue and improved quality of life compared with a placebo, making it one of the first medications to show meaningful benefits for this disabling condition.A widely available antidepressant may provide meaningful relief for people experiencing persistent fatigue from long COVID, according to a global clinical trial co-led by McMaster University. Researchers found that fluvoxamine (sold under the brand name Luvox), an inexpensive medication already commonly used to treat depression and other conditions, reduced fatigue and improved quality of life in adults with long COVID. The randomized, placebo-controlled trial was published in the Annals of Internal Medicine. A Potential Treatment for Long COVID Fatigue Fatigue is among the most frequent and disabling symptoms reported by people with long COVID. For some, the exhaustion is severe enough to interfere with employment, family responsibilities, and everyday activities. Despite the scale of the problem, there are still few treatments supported by strong clinical evidence. "This is an important step forward for patients who have been desperate for evidence-based options," says Edward Mills, senior author, professor in McMaster's Department of Health Research Methods, Evidence, and Impact, and co-principal investigator of the trial. "Fluvoxamine showed consistent and meaningful benefits, and because it's already widely used and well understood, it has clear potential for clinical use." Researchers from Canada, Brazil, and the United States jointly led the study. Clinical sites were located in Belo Horizonte and throughout Minas Gerais, Brazil. The REVIVE-TOGETHER trial brought together investigators from McMaster University, the University of British Columbia, Stanford University, the University of Pittsburgh, Duke University, Georgetown University, and several Brazilian institutions. Testing Fluvoxamine and Metformin The trial included 399 adults in Brazil who had experienced ongoing fatigue for at least 90 days after a confirmed SARS-CoV-2 infection. Participants were randomly placed into one of three groups and received fluvoxamine (sold under the brand name Luvox), metformin (a common diabetes medication), or a placebo for 60 days. "We wanted to test whether two existing, widely available, and affordable medications could help. Both had biological reasons to think they might work against long COVID fatigue, but neither had been rigorously tested for this purpose in a proper clinical trial," says Mills. Fluvoxamine performed better than the placebo in reducing fatigue. The statistical analysis indicated a 99 percent probability that the medication was more effective than the placebo. Participants who received fluvoxamine also reported gains in overall quality of life across several measures. Metformin did not produce the same results. Earlier research found that taking metformin during the initial stage of a COVID infection could lower the risk of later developing long COVID. In this trial, however, the drug provided no meaningful improvement for people who already had established long COVID fatigue. An Adaptive Clinical Trial Design Researchers used a Bayesian adaptive trial design, which allowed them to end individual treatment groups early once the evidence became sufficiently clear. This approach can produce reliable conclusions more quickly than a conventional trial while maintaining scientific rigor. "The trial used a sophisticated adaptive design that allowed it to reach conclusions more efficiently than traditional trials, stopping early when the evidence was clear enough - a design innovation as important as the findings themselves," says Gilmar Reis, lead author, researcher with Cardresearch, a Brazilian clinical research center based in Belo Horizonte. Reis is also a part-time associate professor at McMaster. More Research Is Still Needed Long COVID continues to pose a major global health challenge and is estimated to affect about 65 million people worldwide. Because proven therapies remain scarce, most medical recommendations focus on supportive strategies, including activity pacing and management of individual symptoms. The researchers caution that fluvoxamine is not a complete solution for long COVID. The condition can involve many different symptoms and biological processes, and the medication appears specifically promising for fatigue management. Additional studies will be needed to determine which patients are most likely to benefit, understand why the drug works, and explore whether it could be used alongside other developing treatments. "This trial gives clinicians their first strong evidence for a medication that helps reduce long COVID fatigue. Patients want something they can try today - and this finding brings us closer to that reality," says Jamie Forrest, corresponding author and postdoctoral research fellow at the University of British Columbia. The research was funded by The Latona Foundation.

Amid an ongoing expansion of China’s volume-based procurement (VBP) scheme to lower drug costs, the Chinese government has singled out a fraud case involving a foreign originator drug in a warning to the industry. In an attempt to influence whether a drug gets selected for price bidding, a foreign drug innovator faked doctors’ signatures in a petition, China’s National Healthcare Security Administration (NHSA) said in a post (Chinese) on Tuesday. Among the 78 signatures from 31 hospitals, over 80% were found to be doctored. Some signatures were forged by sales representatives, some used misappropriated images from other sources, and some pointed to individuals that do not exist, according to the agency. As for the few signatures that the experts themselves indeed wrote, the doctors were mostly tricked into signing the document under the guise of survey questionnaires or post-sales follow-up, the agency said. The drug has since been included in the latest VBP batch of 65 drug varieties, which together represent a total market value of nearly 60 billion Chinese yuan ($8.8 billion), according to the NHSA. The VBP, now in its 12th round, is a government-led drug-buying program targeting off-patent medicines. Under the program, generics and the originators offer price cuts to secure procurement contracts with hospitals. The government unveiled the latest list on June 23 and is now in the bidding process. In a statement to local news outlet The Paper , Novartis confirmed it was not the unnamed drugmaker flagged in the NHSA alert. The Swiss pharma’s blockbuster heart failure treatment Entresto (sacubitril/valsartan) is one of the biggest products in this VBP round. According to local reports, Entresto and its generics generated more than 6 billion yuan of end-market sales ($880 million) at public hospitals in China last year, with the Novartis originator accounting for more than 90%. The VBP program now threatens to split up that huge market by rewarding significant shares to companies that offer lower prices. In what’s slated to be an über-competitive bidding process, more than 30 Entresto generics competitors are vying for a place under VBP, according to local drug intelligence database DXY Insight. As part of the largest patent expiry in Novartis’ history, Entresto lost its U.S. market exclusivity last year and has seen major sales declines since. Some uncertainties remain for VBP’s potential impact on Entresto. The Novartis drug is among eight products that carry an asterisk, which indicates ongoing patent disputes. A few days before the revelation of the latest VBP list last month, China’s National Intellectual Property Administration doled out a five-year patent-term extension to Entresto to make up for time lost during its drug regulatory review process, effectively pushing back the expiration of its core patent to November 2031. In a new rule introduced into VBP this time, generic rivals to those asterisked drugs must submit a declaration of non-infringement or be removed from procurement platforms. Takeda’s angiotensin II receptor blocker Edarbi (azilsartan medoxomil) and acid blocker Takecab (vonoprazan fumarate), Eli Lilly’s JAK inhibitor Olumiant, Daiichi Sankyo’s factor Xa inhibitor edoxaban and AstraZeneca’s Xigduo XR (dapagliflozin and metformin extended release) are also included in VBP despite ongoing patent disagreements. Takeda, Bayer and Eisai have also denied they were the company in the NHSA’s announcement, according to The Paper. Bayer’s drospirenone/ethinyl estradiol oral contraceptive, known commercially as Yaz or Yasmin, and its imaging contrast agent Ultravist (iopromide) are included for VBP bidding against generics. Eisai has anti-vertigo medication Merislon (betahistine) and anti-seizure med Fycompa (perampanel) on the list. In addition to the companies above, the 65-item roster includes brand-name products from almost all major pharmas, including Astellas, Fresenius Kabi, GSK, Johnson & Johnson, Pfizer, Merck & Co., Merck KGaA, Otsuka, Sanofi and Servier. Among the smaller firms involved are Cheplapharm, Dr. Falk Pharma and Grünenthal from Germany; Japan’s Maruishi Pharmaceutical, Sumitomo Pharma, LTL Pharma and Minophagen Pharmaceutical; as well as the Wellcome Foundation and Tillotts Pharma in Switzerland.