The Wonder Years

A look into the popularity and potential of GLP-1 weight loss drugs

By Anne-Frances Hutchinson

Hope. It keeps us alive, chasing a future where promise takes root, grows and heals. Hope is risky, challenging our resilience and daring us to hold on through thrilling peaks and solemn valleys. As advances in anti-obesity medicine feed the hopes of millions, we find ourselves at the beginning of an exhilarating climb.

Glucagon-like peptide-1 (GLP-1), a natural incretin hormone produced in the small intestine, helps to regulate blood sugar, appetite, and digestion. that plays a key role in regulating blood sugar, appetite, and digestion. When we eat, GLP-1 is naturally released from our small intestine to stimulate insulin release, suppress the release of the glucagon hormone that raises blood sugar levels, slows down digestion, and reduces appetite.

GLP-1 agonists are a class of medications that mainly help manage blood sugar levels in people with Type 2 diabetes that can also help treat obesity. The first GLP-1 agonist, exenatide, was approved by the FDA for the treatment of type 2 diabetes in 2005.

GLP-1 receptor agonists are medications that mimic the action of this natural hormone. Some have since been approved for weight management in some individuals, kicking a race to discover other possible uses and benefits into high gear.

“These so-called GLP-1-based treatments are blockbusters with the potential to alter societal views of illness and health as profoundly as Valium did in the 1960s or Prozac in the 1980s,” according to the Stat News Obesity Report: How GLP-1 drugs are changing science, business, health care, and society.

Several factors contribute to the widespread interest in these drugs. Because supply chain issues and other restrictions have improved, companies are making big investments to increase production and ramping up M&A activity with compatible drug makers.

Additionally, the scope of these drugs has widened considerably; data shows GLP-1 can be used to treat coronary heart disease, stroke, high blood pressure, kidney disease and sleep apnea, and may even have potential to fight cancer, osteoarthritis, addiction, and neuropsychiatric conditions. Most are in the clinical trial stage, and many hoped-for indications will likely take years to achieve.

Welcome to a new era of possibility

“When you think of the downstream health issues caused by living with obesity… if we actually implement these drugs the right way, we can save our health care system because of all of the downstream conditions that these are shown to improve,” said Dave Knapp, founder of On The Pen™ Obesity Medicine News. He is also the host of the On The Pen podcast, and has built a community of 160,000 users of injectable and other forms of GLP-1.

“We are seeing a pivot from the two largest players in the obesity medicine market, Eli Lilly and Novo Nordisk,” he added, noting that both firms have seen the tremendous potential for treating metabolic issues as well as obesity. “But we’re also learning that these hormones are targeting areas of the brain that affect other things.”

There’s a drive to make GLP-1-based medicines more convenient to take. At present, most of the available drugs are in liquid form and must be injected, but several companies are in clinical trials to develop delivery in pill form. As we go to press, only Novo Nordisk’s semaglutide, Rybelsus, has been FDA approved and on the market; they are awaiting FDA approval on higher doses of oral semaglutide specifically for obesity treatment. Work is also being done to make the dosing more patient-friendly. Some medicines must be taken twice daily, others weekly, and potentially,  researchers aim to monthly or less.

Potential users have expressed concern about the loss of lean muscle mass that results from rapid weight loss. Lean body mass can account for up to 15 to 40% of total weight loss from GLP-1 therapies. “How do we make sure that weight loss is good weight loss,” Knapp said. “How do we make sure that it’s not 30% muscle mass? How do we preserve the body composition in the process of bringing people’s weight down?”

The American Diabetes Association (ADA) is searching for answers to these concerns. “As we enter a new era of obesity treatments, it’s vital to focus not just on the amount of weight lost, but on preserving muscle mass and gaining the health benefits that result from treating obesity,” said Samar Hafida, the Vice President of Obesity Association, a division of the ADA. “We are championing research to ensure people living with obesity can have access effective treatments to reduce adiposity while maintaining muscle mass critical to their well-being, and supporting durable long-term outcomes.”

A study demonstrating the effectiveness of combining Eli Lilly’s muscle loss preventive, bimagrumab, with Nova Nordisk’s semaglutide in overweight or obese adults found that the combined therapy led to greater reductions in weight, body fat, visceral fat, and markers of inflammation compared to either treatment alone.

The ADA reported that the combination therapy yielded 92.8% of total weight loss from fat mass compared to semaglutide alone (71.8%) and an overall decrease in bodyweight (22.1%). With the use of bimagrumab alone, 100% of weight loss was attributed to fat mass and there was an increase of 2.5% total lean mass.

Setting aside the potential treatments for improved health beyond obesity, these drugs have a depth of meaning for people who struggle with it. Knapp pointed out that the one consistent experience among GLP-1 users is the joy of getting their life back. “You can experience life in a way that you could not before, whatever that means for you,” he said.

Knapp, a self-proclaimed GLP-1 evangelist, believes that the positive impacts of these treatments often get short shrift in a media climate where controversy has become the order of the day.

“There needs to be a counter to the media narrative,” he concluded. “Are there negative sides of this? Yes. Are there people not living with obesity using GLP-1 to lose 10 pounds? Yes. But, at the end of the day, it’s hard to refute anybody’s decision to be on these medications because the science seems fairly irrefutable at this point that most everybody would benefit from them in one way or the other.”

Along with the dramatic changes in health and wellness that GLP-1 may achieve, the ultimate medicine  is one everybody needs regardless of age, size, or condition: hope.