A New Obesity Drug on the Block: Is This Medication a Game Changer for Weight Loss?
With rates tripling over the past four decades, over 73% of adults in the United States are now classified as overweight or obese. As one of society’s most considerable public health problems, having an unhealthy body weight accounts for 4 million premature deaths globally each year.
In a 2018 study, American adults who were classified as obese had a 27% increased risk of dying during the 24-year-long study, with those with severe obesity almost doubling their risk of premature mortality. In addition to causing reduced life expectancies, obesity is associated with a markedly increased risk of developing other chronic diseases that can lead to premature mortality, including type 2 diabetes, cardiovascular disease, and stroke, to name a few.
As many of the current weight loss medications on the market either cause significant adverse effects or have low efficacy, doctors and patients alike hope to identify new treatments that lead to meaningful and safe weight reduction. Now, a primarily United Kingdom-based research team — dubbed the STEP 1 Study Group — may have done just that, with a prescription drug called semaglutide.
STEPping up to fight obesity
Standing for Semaglutide Treatment Effect in People with Obesity (STEP), a recent study in the New England Journal of Medicine, authored by Wilding and colleagues, used semaglutide to produce an astonishing 20% reduction in body weight in almost one-third of the participants. With these results, people with obesity that haven’t responded favorably to other treatments may soon see dramatic improvements in overall health outcomes — with extended lifespans to boot. Summarized succinctly by one of the study’s authors, Professor Rachel Batterham states, “No other drug has come close to producing this level of weight loss – this really is a game-changer.”
This game-changing drug works by imitating a naturally occurring hormone called glucagon-like-peptide-1 (GLP-1). Responsible for numerous vital aspects of metabolism, GLP-1 inhibits caloric intake by acting on the brain’s appetite centers and slowing down gastric emptying — the speed at which food moves from the stomach through the rest of the gastrointestinal tract. With slower gastric emptying, food remains in the stomach longer, leading to feelings of fullness and reduced caloric intake.
Semaglutide is already an FDA-approved drug for treating type 2 diabetes at a 1 mg weekly dose, which is lower than that of the present study. A previous phase II clinical trial from the same team verified semaglutide’s safety and efficacy, as the drug-induced weight loss in adults with obesity and type 2 diabetes. In the present study, STEP enters its third trial phase, assessing a dose of 2.4 mg of semaglutide administered subcutaneously (under the skin) by self-injection once per week in overweight and obese adults, both with and without other health complications.
Except for people with type 2 diabetes, who were excluded from this study, about 75% of these participants had another coexisting condition, like heart disease, high cholesterol, or hypertension. This 68-week-long study was a randomized, double-blind, placebo-controlled trial — the best of the best when it comes to health research — that took 1,961 overweight or obese adults from 16 countries that had reported previously unsuccessful attempts at losing weight. Both the treatment and placebo groups were also encouraged to reduce their caloric intake by 500 calories per day and increase physical activity to 150 minutes per week.
The significant successes of semaglutide
After taking semaglutide for 68 weeks, the changes in body weight were striking. The treatment group experienced an average weight loss of 15%, while the placebo group lagged behind at 2.4%. This translated to 15.3 kg (33.7 pounds) lost in the semaglutide group and 2.6 kg (5.7 pounds) in the placebo group. Notably, almost one-third of those in the treatment group lost 20% or more of their body weight, compared to 1.7% of the placebo group. Additionally, 86% of the semaglutide group lost 5% of their body weights, compared to 32% in the placebo group. As their baseline weights averaged 105 kg (231 pounds), both weight reductions — 5% and 20% — are clinically significant and meaningful.
Other health outcomes improved after taking weekly semaglutide, including reductions in waist circumference, blood pressure, lipid (cholesterol) and glucose levels, and C-reactive protein — a marker of inflammation. Of the people in the treatment group who had prediabetes at the start of the study, 84% had their blood sugar levels reverted to normal levels. Additionally, the semaglutide participants also had improved scores of physical and mental functioning.
Is semaglutide a magic pill?
While it’s too soon to tell if semaglutide is the silver bullet we’ve been searching for, this research team has gotten one step closer to finding a cure for obesity. It’s important to note that semaglutide did produce more significant adverse effects than the placebo group — most often gastrointestinal-related disturbances, like nausea, vomiting, diarrhea, and constipation. However, these side effects were typically transient and moderate. A benefit of the once-weekly regimen, rather than a usual daily dose, is that these side effects are occurring less often, in addition to making it easier for patients to adhere to the dosing schedule.
While these results were incredibly promising, it’s still unknown if this higher dose of semaglutide would potentially produce more serious adverse events down the road. As the participants in this study started to regain some of their lost weight pretty quickly after stopping the semaglutide, it would likely be a lifelong endeavor of taking this medication to keep the weight off.
And, with that, comes a cost — insurance companies in the past have not paid for other weight-loss drugs on the market, and the lower dose of semaglutide already costs up to $1,000 per month for people with type 2 diabetes. However, researchers believe that this study’s high efficacy and game-changing results may lead to insurers being more likely to cover the drug.
Lastly, while we know that not all of semaglutide’s successes came from the encouraged lifestyle changes (based on the differences from the placebo group), some of the benefits may have So, it is still possible that people who take the drug without reducing caloric intake or increasing activity level would not see weight loss as substantial as these study participants.
Despite these limitations, this study provides substantial evidence that semaglutide — or other GLP-1-mimicking drugs — could soon be used across the globe for treating obesity and giving hope to people who have not been able to lose weight on their own. With these potentially wide-reaching effects, a subsequent increase in lifespan could be not too far along, as declining obesity rates will also reduce the incidence of other diseases that lessen longevity.
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O'Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active-controlled, dose-ranging, phase 2 trial. Lancet. 2018;392(10148):637-649. doi:10.1016/S0140-6736(18)31773-2
Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity [published online ahead of print, 2021 Feb 10]. N Engl J Med. 2021;10.1056/NEJMoa2032183. doi:10.1056/NEJMoa2032183
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