Why this pill could be a gamechanger in fight against obesity, diabetes

medium120408412A daily pill may be as effective in lowering blood sugar and aiding weight loss in people with Type 2 diabetes as the popular injectable drugs Mounjaro and Ozempic, according to results of a clinical trial announced by Eli Lilly on April 17.The drug, orforglipron, is a GLP-1, a class of drugs that have become blockbusters because of their weight-loss effects. But the GLP-1s on the market now are expensive, must be kept refrigerated and must be injected. A pill that produces similar results has the potential to become far more widely used, though it is also expected to be expensive.Lilly said it would seek approval from the US Food and Drug Administration (FDA) later this year to market orforglipron for obesity and early in 2026 for diabetes. Industry analysts expect the drug to win approval sometime next year and to eventually become a major blockbuster. Eli Lilly is not expected to announce a price for the drug until after it wins approval.“What we are seeing start to play out is a fight for the future of the obesity market,” said Craig Garthwaite, a healthcare economist at Northwestern University.The company announced a summary of its results in a news release, as drug companies are required to do immediately after they receive study results that could affect their stock price.But Lilly did not release the underlying data from its trial and the results it disclosed had not been examined by outside experts. The company said it would present detailed results at a meeting of diabetes researchers in June and would publish them in a peer-reviewed journal.The clinical trial involved 559 people with Type 2 diabetes who took the new pill or a placebo for 40 weeks. In patients who took orforglipron, A1C, a measure of blood sugar levels over time, fell by 1.3% to 1.6%. Ozempic and Mounjaro generated similar results in unrelated trials. For 65% of people taking the new pill, blood sugar levels dropped into the normal range.Patients on the new pill also lost weight — an average of 7.25kg for those taking the highest dose. Their weight loss was similar to that achieved in 40 weeks with Ozempic but slightly less than with Mounjaro in unrelated trials.Side effects were the same as those with the injectable obesity drugs — diarrhoea, indigestion, constipation, nausea and vomiting.It is possible that when the drug is used in much larger numbers of patients, the benefits could be smaller and the side effects worse.Eli Lilly is at the front of a small pack of companies racing to develop GLP-1 pills. There have been major concerns that such pills could cause harsh side effects that discourage patients from taking them. Earlier this week, Pfizer said it had decided to stop developing such a pill after a trial participant experienced a “potential drug-induced liver injury”.But in Eli Lilly’s trial, orforglipron did not show any adverse effects on the liver. medium nocaptionhttp://youtu.be/SpCJpiHxI2M?si=o0UQwnxYVXERVOdAEli Lilly’s stock surged on the encouraging data. It closed up 14% on April 17, adding $100bn to the company’s market value.This was the first of seven main clinical trials of orforglipron to report results. Some of the others are testing the drug for weight loss in people without diabetes. Results in patients with obesity are expected later this year.If the drug is approved for obesity and diabetes, said Dr Daniel Skovronsky, Lilly’s chief scientific officer, the company is confident it will have sufficient amounts of the pills to meet demand.“In the coming decades, more than 700mn people around the world will have Type 2 diabetes, and over a billion will have obesity,” Skovronsky said. “Injections cannot be the solution for billions of people around the world.”Some 12% of American adults say they have taken a GLP-1. About 40% of Americans are obese, and more than 10% have diabetes, most of whom have Type 2, according to the Centers for Disease Control and Prevention.The most popular injectable drugs already on the market are made by Eli Lilly, which sells its drug as Zepbound for obesity and Mounjaro for diabetes, and Novo Nordisk, which sells its medicine as Wegovy for obesity and Ozempic for diabetes.As demand for these drugs has surged in the past few years, the ballooning costs have hit employers and government programmes that were already struggling with rising prescription drug costs. Orforglipron is now poised to expand the market and worsen the strain on their budgets.In a way, the very existence of orforglipron is a triumph of modern chemistry. The injectable GLP-1 drugs are peptides — small fragments of proteins. (GLP stands for glucagon-like peptide.) Peptides are digested by the stomach. So, in order to make an oral GLP-1, chemists had to find a way to make a nonpeptide that acts exactly like a peptide. Researchers at Chugai Pharmaceutical, a Japanese company, figured out a way, licensing their drug to Lilly in 2018.The solution was to find a small molecule — thousandths of the size of a peptide — that sinks into a tiny pocket in the protein that is the target for GLP-1s. When it sinks into the pocket, the protein changes shape just as it does when a GLP-1 binds to the whole protein.Finding that small molecule, Skovronsky said, was “the holy grail”.The result — a pill that can be taken at any time of day, with or without food — is almost unheard-of in the world of peptide drugs. Insulin, probably the most common peptide drug, has been around for more than a century. It is still only an injectable despite intense efforts by scientists to make an insulin pill. So is human growth hormone. So are drugs used to treat a wide variety of diseases, including arthritis and cancer. medium nocaptionhttp://youtu.be/DM5cGuddYww?si=Rm23B5vEsJWH90EONovo Nordisk has a GLP-1 pill, Rybelsus, but it contains the GLP-1 peptide, so it must be taken in large doses and is not as effective as the injectables because most of it is digested.But for patients with diabetes and those struggling with obesity, a pill that can replace an injection can be transformative, for several reasons.One is that it can make treatments attractive to those who cannot bear the very idea of injecting themselves.Dr Ronald Kahn, a professor of medicine at Harvard University and chief academic officer at Harvard’s Joslin Diabetes Center, said he had many patients who were reluctant to inject themselves with Ozempic or Mounjaro.A pill, he said, “would definitely be preferred by most people”.Dr Sean Wharton, director of the Wharton Medical Clinic in Burlington, Ontario, has a broader hope. Wharton, who enrolled patients in Lilly’s study of orforglipron for obesity, said a pill could potentially bring GLP-1 treatment to underserved populations throughout the world.“It can be easily made in a factory and shipped everywhere,” he said. It should cost much less to make than peptides and does not require packaging in special injection pens. It does not have to be kept refrigerated.For now the drugs are only available to a small portion of people who have insurance coverage or can afford to pay for them out of pocket. Only rich countries have had access to them.That is beginning to change: Eli Lilly recently launched its injectable GLP-1 drug in India. Patients here would generally have to pay as much as ₹17,000 a month for the drug, a price far out of reach for most people in India. As soon as next year Novo Nordisk’s Ozempic and Wegovy are expected to go generic in some countries, though not in the US.With orforglipron, “we have a chance of a medicine being given to millions and millions of people”, Wharton said.But that depends on Eli Lilly and how it chooses to price and distribute its drug.“That’s why I emphasise the word ‘chance’,” Wharton said.