Glucagon-Like-Peptide-1(Original Biomedicals)

Ozempic and GLP-1 drugs like it became household names due to their potent weight loss benefits, and are now proving useful in a slew of other chronic conditions.Women are noticing other benefits, too, including some that may be flying under pharmaceutical companies radars. Reports have emerged of unexpected pregnancies among women on GLP-1 treatment, and researchers have mused of possible effects on fertility or on hormonal disorders as well.Melanie Cree, a pediatric endocrinologist at Children's Hospital Colorado, is one physician looking into this question. Working with her colleagues, she conducted a randomized trial testing semaglutide, the ingredient in Novo Nordisks Rybelsus and Wegovy, in women and adolescents with polycystic ovary syndrome, or PCOS.Cree said this research provides evidence of what these medications can do for PCOS, reproductive measures and periods specifically. While results from Crees first trial arent yet published, they were encouraging enough to spur Cree to launch another, larger trial testing the link between weight loss, metabolic changes and reproductive function in people with PCOS.PCOS is a set of symptoms caused by a hormonal imbalance, usually overproduction of testosterone, that disrupts ovulation. The condition leads to cysts developing in the ovaries, which in turn changes an individuals menstrual cycle and may result in infertility. People with PCOS can also develop insulin resistance, increasing the risk of Type 2 diabetes and other cardiometabolic issues. The disorder is typically diagnosed during adolescence.There is no standard treatment for PCOS, and diagnosis can often be time-consuming and difficult. The World Health Organization estimates 70% of affected women remaining undiagnosed globally.[Researchers] haven't pinpointed the reason or background etiology for the condition, said Pardis Hosseinzadeh, an assistant professor of gynecology and obstetrics at Johns Hopkins School of Medicine. So obviously, when that's not fully discovered yet it gets hard to treat PCOS, because it affects many different systems in the body.Depending on symptoms, doctors may recommend different medications or other interventions, such as weight management or birth control that helps with ovulation, mood changes and hormonal acne.Studies like mine and my colleagues are very important because there are currently no FDA-approved medications for PCOS, Cree said.Weight loss can improve symptoms of PCOS and is therefore usually an objective of treatment. Often, metformin, a diabetes medication, is prescribed, but other lifestyle interventions or even bariatric surgery may also be used.One of the primary reasons I started looking at GLP-1s is because there is this tight association between weight, PCOS hormones and PCOS periods, Cree said.Endocrinologists and doctors helping women with PCOS are well aware of the difference weight loss can make in menstrual cycles and hormone regulation. Last year, the American Society for Reproductive Medicine, or ASRM, updated its guidelines for treating PCOS, which had been the same since 2018. The new guidelines now note the potential for GLP-1 drugs like semaglutide to help control weight.Chau Thien Tay, an endocrinologist at Monash Health who contributed to the new guidelines, told BioPharma Dive that weight loss therapies were considered in the previous framework. The inclusion of GLP-1s this time around simply reflects a shift in the therapeutic landscape guided by recent advancements and clinical evidence, she wrote.With her new study, Cree aims to study whether PCOS symptoms are eased with weight loss, regardless of method, or whether GLP-1 drugs specifically can help with hormonal disorders.The 10-month trial, which aims to recruit 80 girls and women between 12 and 35 years old, will test the effects of injected semaglutide on ovulation. It will also assess whether age or metabolic and hormonal changes could predict the response to GLP-1 treatment.By going across that reproductive lifespan, [the study] can help us determine and move towards personalized medicine for individuals by understanding if there is a difference in the response between teenagers and adults, Cree said.Based on the previous, smaller study using oral semaglutide over a shorter time span, Cree believes the injectable version will help regulate ovulation.A lot of the patients who have PCOS, or who struggle with PCOS or other issues like insulin resistance and obesity, may have irregular cycles from not having regular ovulation, said Hosseinzadeh. It's been very well known to [healthcare providers] that weight loss of up to 5% of body weight in patients with PCOS can help regulate their cycles by resuming regular ovulation.GLP-1 drugs hoped-for effect in PCOS could be related to their purported impact on fertility, which researchers are now looking at more closely following widespread reports on social media.While theres thought to be a link between weight loss and fertility or pregnancy outcomes, the strength of the association is still unclear.Some doctors theorize that unexpected pregnancy in people taking GLP-1s may be due to the drugs impact on the effectiveness of oral birth control, as it slows down the digestive process.Wegovy, which contains semaglutide and is labeled for obesity, comes with a warning to discontinue use two months prior to planning to become pregnant. ASRMs PCOS guidelines also advise contraception for women taking GLP-1s due to limited safety data during pregnancy.A spokesperson for Novo Nordisk said in an email that, based on animal studies, Wegovy may present risks to the fetus during pregnancy. The company has established a pregnancy registry for Wegovy to collect safety information.The spokesperson added that Novo has not conducted studies to assess the efficacy and safety of our FDA-approved GLP-1 medicines in patients with PCOS, and have no immediate plans to do so.A spokesperson for Eli Lilly said the company has not studied the impact of tirzepatide on fertility in humans. (Tirzepatide is the drug ingredient in Zepbound, the medicine Lilly sells for obesity.) Lilly encourages pregnant people exposed to Zepbound to contact the company. The spokesperson did not answer BioPharma Dives questions on PCOS.The companies positions arent atypical. Pregnant women are often excluded from clinical testing due to the risk of potential harm to the fetus. And the dramatic weight loss that GLP-1 treatment can induce may not be healthy during pregnancy.I think its still not prime time to say that [weight loss drugs] could be used for other indications or are fully safe to be used right before trying for pregnancy, or for patients who are trying for pregnancy, Hosseinzadeh said. So we still need some more data. But we also don't have any data to say that they're harmful.Such information is important, as GLP-1 drugs are proving particularly attractive to women. While obesity rates between men and women are similar, prescriptions for weight loss medicines like Ozempic skew heavily toward women, according to recent U.S. data cited by Reuters. Earlier data from pharmacy benefit manager Prime Therapeutics found a similar imbalance. Clinical trials testing Wegovy and Zepbound for obesity enrolled more women than men, too.It may be that the GLP-1s can help [PCOS] patients in the long term, Hosseinzadeh said We tend to get really focused on the effects on fertility and reproduction during the reproductive years, but we're looking at the middle part of the spectrum. This is a condition that affects a woman throughout her life. '

Novo Nordisk has had much success marketing Ozempic in China. Now the company will try to do the same with its obesity drug Wegovy as China's National Medical Products Administration has approved the GLP-1 treatment. On the market for three years in China, Novo Nordisk’s diabetes drug Ozempic (semaglutide) is racing toward blockbuster sales in the world’s second most populous country. With that success in place, the Danish company looks to double down with its obesity treatment Wegovy. On Tuesday, China’s National Medical Products Administration (NMPA) blessed Wegovy with marketing approval to treat people with a body mass index (BMI) of at least 30 or between 27 and 30 for those with one weight-related risk factor. It will be marketed as NovoCare in China. The drug is the same compound, semaglitude, as that used in Ozempic. In response to the nod, Novo’s share price increased by 3%. Obesity is a growing problem in China. In 2022, more than half of the country’s adults were overweight or obese. China has more people with type 2 diabetes and obesity than any country in the world. In approving Wegovy, the NMPA cited its ability to achieve an average weight loss of 17% and the associated benefits it provides. "Up to now, there is still a lack of effective clinical drug treatments for obese patients in China, and there is a huge medical need to be met," Chen Wei, of the Peking Union Medical College Hospital, said in a release: "In view of the clinical situation that there are very limited drugs approved for the treatment of obesity in China in the past 20 years, new medical weight loss drugs can provide patients with safe, effective and convenient treatment options." Novo will have to act quickly to maximize sales of Wegovy in China however, as its patent on semaglutide is set to expire there in just two years—or even sooner if an upcoming court ruling goes against the company. As a result, drugmakers in China are set to flood the market as at least 15 GLP-1 biosimilar candidates are in development, according to a story reported earlier this month by Reuters. In Europe and the United States, Novo has exclusive rights to semaglutide until 2031 and 2032 respectively. The approval comes three months after Novo revealed that it was investing 4 billion yuan ($556 million) in its 30-year-old flagship manufacturing site in Tianjin, China., with the upgrades due for completion in 2027. Last year, Novo more than doubled its China sales of Ozempic to 4.82 billion kroner ($693 million). The company now faces competition in the indication as last month the NMPA signed off on Eli Lilly’s dual action GLP-1/GIP diabetes drug Mounjaro (tirzepatide). The commercial name for the treatment in China is MuFengDa.