Off-label use of semaglutide (Ozempic; Novo Nordisk) for the treatment of obesity has been blamed on the recent shortage of drug supply, which is indicated for type 2 diabetes. , many experts say that the drug for satiety and others like this are game-changing additions to the treatment of obesity.
Demand for glucagon-like injectable peptide-1 (GLP-1) agonist semaglutide has skyrocketed in the past 12 months following a large manufacturer-sponsored randomized trial (STEP 1), published in the New England Journal of Medicine (NEJM). ), who found that 2.4 mg of semaglutide once a week was associated with an average weight reduction of 15% at 18 months, compared with 2.4% with placebo in overweight or obese people.
However, access issues have quickly arisen. In Australia, where 0.5 mg and 1 mg semaglutide is approved and subsidized for the treatment of type 2 diabetes, the Therapeutic Goods Administration (TGA) warned in May that off-label prescribing to people with obesity had caused a shortage of supply. . Doctors were told to limit the prescription of semaglutide to its approved use in people with diabetes.
The manufacturer, Novo Nordisk, told InSight + that it has applied for registration of 2.4 mg semaglutide at the TGA for weight management with the brand it already uses abroad, Wegovy.
There is also another GLP-1-based drug on the horizon for the treatment of obesity: tirzepatide. A phase 3 trial published in the NEJM on June 4 found that half of obese patients randomly assigned to moderate doses of tirzepatide once a week lost at least 20% of their body weight at 72 weeks, compared with only 3% of the placebo group. Both groups received intensive lifestyle intervention. The drug has not yet been approved anywhere in the world for the treatment of obesity, although it has recently been approved in the United States for type 2 diabetes.
However, even if new GLP-1 agonists are indicated in Australia for weight loss, experts fear their price will put them out of reach for most obese patients.
Dr Priya Sumithran, an endocrinologist and leader of the Obesity Research Group at the University of Melbourne, summed up the hope and concern felt by researchers in the field.
“In recent years there has been a great change and optimism in the field of diabetes and obesity as to what is available and what will be possible, and we now have several good treatment options imminent,” he said. tell InSight +. “However, the big question now is whether patients will be able to afford access to it.
“The way these drugs are funded or reimbursed will have to change if people can benefit equitably,” he said.
Inequality of access
Patients with insufficiently controlled type 2 diabetes can access semaglutide with the Pharmaceutical Benefits Scheme (PBS) for $ 42 a month or $ 6.80 in grant.
Obese people, on the other hand, pay about $ 133 a month if they access the drug off the label. It is a treatment that most obese Australians (30% of the population) cannot afford, especially given the high prevalence of obesity among low-income people.
However, many who can afford it will pay, as semaglutide is associated with much greater average weight loss compared to placebo than the currently registered drugs for obesity in Australia: Phentermine ( Duromine; iNova), naltrexone and bupropion (Contrave; Currax), liraglutide. (Saxenda; Novo Nordisk) and orlistat. Lyraglutide, the only registered GLP-1 agonist for obesity, costs three times as much as semaglutide ($ 387) and has the disadvantage of being taken daily instead of weekly.
Novo Nordisk, a manufacturer of both semaglutide and liraglutide, told InSight + that the two drugs were not equivalent.
“Saxenda (liraglutide 3 mg) is the only GLP-1 approved for use in weight loss in Australia,” the company said in a statement. “Saxenda (liraglutide 3 mg) is a different molecule with different dosages and different indications for Ozempic (semaglutide).”
However, Professor Katherine Samaras, an endocrinologist and researcher at St Vincent’s Hospital in Sydney, said the STEP 1 study provided ample evidence to support the prescription of semaglutide for the treatment of obesity, as many specialists and GPs are already doing.
“Why should obese people pay three times the cost of a drug when there is an effective and cheaper medication?” he told InSight +.
Professor Samaras, like many of her colleagues, believes that barriers to accessing medications for obesity represent a major equity issue.
However, the Pharmaceutical Benefits Advisory Committee (PBAC) has estimated that subsidizing semi-swallowing for obese Australians would cost more than $ 1 billion a year for 6 years in the current market.
The PBAC considered semi-swallowing for obesity at its March 2022 meeting and decided not to recommend the requested list. Doing so would have required “an extremely high investment” with “very uncertain implications for PBS and the broader health budget,” the PBAC said.
He also questioned the long-term efficacy of the drug in the difficult outcomes, saying the sponsor’s modeled reductions in comorbidities with ongoing treatment were “very uncertain” since no long-term data were available.
Dr. Liz Sturgiss, a general practitioner and researcher at Monash University, noted that the semaglutide STEP 1 study showed “some improvements in cardiovascular risk factors, such as blood pressure, glycated hemoglobin, and cholesterol treatment. “.
“Although the trial only reported most of these as secondary criteria, rather than as part of the results, it is promising, as it is one of the first trials of obesity medications seeking different results. of weight “.
He added: “Equity is a major issue in managing obesity in Australia.”
A disease that kills
Professor Samaras said part of the problem of access to medicines for obesity and also bariatric surgery was reduced to the stigma surrounding the disease.
“There are misleading narratives in the media that obese people only want to lose weight for aesthetic reasons or who are to blame for their condition,” he said.
“The fact is, obesity kills people,” he said. “Today’s major cancers in Australia have obesity accelerating them, and obesity is a risk factor for diabetes, cardiovascular disease, fatty liver disease and cirrhosis and arthritis.”
Professor Samaras criticized a “monocular glucocentric view of obesity,” saying that many obese people maintained normal glucose levels but had significant comorbidities associated with obesity or were at risk for obesity.
Even modest weight reductions could alleviate significant health loads, Professor Samaras said. For example, a 5 kg weight reduction may help some patients control their blood pressure and lipids.
Other patients may have larger weight reduction goals to access interventions such as heart transplantation or to ensure good results after cancer therapy or joint replacement, he said.
The place of medication
Professor Samaras said the new GLP-1 agonists were good additions to the treatment armament for obesity, along with lifestyle interventions and, if necessary, bariatric surgery.
“For people who have already tried dieting and exercising over and over and over again, add what is necessary and safe, commensurate with the impact of obesity on that person,” he said.
Bariatric surgery now had 20-year results reported in the literature; however, with almost no access to surgery in the public system, it was also beyond the reach of many patients, he said.
Professor Samaras said GLP-1 agonists should be considered before a bariatric surgery trial.
The new drugs could also be useful for people who regained weight in the years following successful bariatric surgery, he said.
Evidence was also accumulating to support the use of GLP-1 agonists to mitigate the obesity-inducing effects of antipsychotic drugs, according to Professor Samaras, who is participating in a joint prescribing trial of semaglutide and clozapine.
Professor Samaras stressed that no medicine or surgery would work without a lifestyle change.
This was, in fact, one of the reasons the PBAC did not recommend the semaglutide list for obesity: it was “unlikely” that the benefits of semaglutide observed in clinical trials would be “fully completed in Australian practice”. without intensive diet and co-administered exercise advice. ” in the test program, ”said the PBAC.
Risks and contraindications
The main side effects of new GLP-1 receptor agonists are gastrointestinal: nausea, diarrhea, and constipation.
In the semaglutide obesity study, 4.5% of treatment arm participants discontinued treatment due to gastrointestinal events.
Professor Samaras commented: “Some people may be exquisitely sensitive and may take the lowest dose and vomit for a week. They may respond better to a different medication.”
There are also questions about the safety of GLP-1 agonists in the context of significant alcohol consumption given the low risk of pancreatitis, Professor Samaras said. However, he added that, anecdotally, semaglutide could reduce a patient’s interest in alcohol.
Professor Samaras said the biggest concern with the new drugs was the lack of long-term safety data. The longest follow-up period is only about 3 years for semaglutida.
“However, it must be remembered that obesity itself is not a benign condition,” he added.
In general, NPS MedicineWise notes that there is no legal impediment to prescribing off-label medications, but it is the prescriber’s responsibility to defend their prescription for an indication not listed in the product information.
A TGA spokesman said the shortage of semaglutide is expected to be resolved by August 31, 2022.
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