Suppressing Appetite, Maintaining Weight Loss

[The drug manufacturer is ramping up manufacturing capacity] to meet the extraordinary demand for the product, and commercial launch in Canada will only happen once we have sufficient supply to meet the needs of Canadian patients."

Mounjaro has not been submitted for Canadian regulatory approval for weight management, and although it may be submitted for this indication in the future we are not permitted to speak about the product, off-label."

Eli Lilly Pharmaceuticals

"You can think of a world where we don't have obesity anymore, or it's very uncommon."

 "You could imagine, in some people they may require a lot more of those signals to override a brain that's hardwired to feel hungry more, to feel less full."

"We're able to now manufacture something that everybody is producing, and we're actually able to keep it to the brain and the system a lot longer."

Dr. Nadia Khan, general internist, professor of medicine, University of British Columbia

"[There is a potential magnitude ] of misuse and abuse of these medications by folks who clearly do not have a medical need to lose weight."

Dr. Arya Sharma, professor emeritus of medicine, University of Alberta

Mounjaro is being touted as the most powerful weight-loss drug available. Credit: Marco Verch, cc2/Flicker

 

In the United Kingdom, concerns radiate around the "medicalization" of obesity and well-orchestrated marketing campaigns by drug manufacturers. The issue is that on a global scale, over 650 million adults fall into the obese category The current hype over  a type of drugs that have proven to reduce weight gain through the administration of a once-weekly pharmaceutical has excited the world's community of overweight individuals, raising expectations of a miracle cure for obesity.

Restrictive diets appear to have had their day. Coupled with exercise regimens diets purporting to be successful in restraining weight gain come and go, as do prescriptions for medications meant to help in the eternal battle of shedding excess weight, and failing to meet excited expectations. Now, for the first time the heavily overweight have discovered an ally in a new class of drugs that help people to obsess less about food, while steadily helping them to lose weight.

Ozempic, a drug formulated to treat people with Type II diabetes, used off-label, has swept the obese community with promises of solving all their weight-related problems. The weekly injections have proven hugely successful and prescriptions for the drug have left short supplies for people with diabetes, its original treatment purpose. Now, a new drug has entered the scene, Mounjaro, yet another Type II diabetes drug.

Approved both in Canada and the U.S. for diabetes management, the drug will be approved for weight loss purposes shortly in the United States where it was granted a speedy review by the Food and Drug Administration. Mounjaro, according to published results, offers a more significant reduction in weight than Ozempic, or its sister drug Wegovy. 

The Economist and other media outlets have announced that the new era of AOMs -- anti-obesity medications -- could  result in ending obesity. However, the costs involved in this type of therapy could very well make the drugs far too costly for many people to access them. Mounjaro and other anti-obesity medications do have the potential -- on the other hand, according to a review in The Lancet -- to effectively tackle obesity.

 

Jose Luis Pelaez/Getty Images

 

Demand for Ozempic and Wegovy leading to shortages, does require a similar drug devoted entirely to weight loss, that would not disrupt the supply of medications for people with diabetes. Moujaro was approved by Health Canada for people with Type II diabetes; even so, doctors prescribe it "off-label" (for uses other than those formally endorsed by the drug regulator). 

Over 3.5 million prescriptions to the value of close to $1.2 billion were filled by retail pharmacies in Canada last year, up from over 81,000 orders in 2018. Like Ozempic, the brand name for a molecule called semaglutide, Mounjaro targets a hormone called GLP-! that signals fullness and curbs appetite. Mounjaro whose chemical name is tirzepatide, targets a second hormone, GIP, which has a large role in body weight and food intake. It is the gut-brain connection that both hormones affect.

People on Mounjaro lost on average 19.5 to 21 percent body weight over a period of 72 weeks, depending on the dosage; "an unusually substantial degree of weight reduction for a weight-loss drug", according to a study sponsored by Eli Lilly. Close to the numbers observed with bariatric surgery. Over half of those on the highest doses experienced a reduced body weight of 20 percent or more.

And then there are side effects that accompany all medications; with the new drugs the most common are nausea, diarrhea and other gastrointestinal problems. The drugs, moreover are meant to be taken for a lifetime. Once off the drugs people regain two-thirds off lost weight within a year's time. The current consensus is that these drugs appear "vastly improved" over what was available before their advent.

The brain's hypothalamus controls the regulation of appetite; how full or hungry we happen to feel at any given time. The mesolimbic system controls appetite and pleasure, which cannot be altered, but the hypothalamus receives signals from the stomach, intestine and fat tissue. So that when food enters the stomach, ghrelin, the hunger hormone, gets suppressed, and two hormones -- GLP-1 and GIP  are released from the intestine, signalling fullness to the brain.

On injections with Ozempic or Mounjaro, bodies produce more of the hormones regulating hunger and feelings of satieyt. They also act on the gut to slow gastric emptying. Mounjaro appears to lead to greater reduction in total body fat mass than Ozempic. What is unknown is whether people will take to the weekly injections, along with the big question mark about long-term affordability. 

 

Then there are oncerns over whether long-term use possibly revealing more serious side effects, such as heart valve damage, stroke and cardiovascular death such as ensued with the fenphen regimen.