Semaglutide for Treatment of Obesity

We now have a “Miracle Pen”! A pre-filled pen that is loaded with a brand new addition to the armamentarium of medicines to aid in weight loss. It is Semaglutide (brand name Wegovy) that was FDA approved in June 2021. Semaglutide is an injection that is self-administered once weekly for chronic weight management in adults. It belongs to the same group (GLP-1 agonist) as Liraglutide (Saxenda) which was approved in 2014. Adults with obesity (BMI 30 or more) or overweight (BMI 27-29) with at least one weight-related condition (such as high blood pressure, type 2 diabetes, or high cholesterol), are eligible to receive it if there are no contraindications.

Semaglutide is the first and only once-weekly injectable available for the chronic management of obesity. Semaglutide is a “Glucagon-like Peptide -1” (GLP-1) agonist, which means that it works similarly to the gut hormone GLP-1 to decrease hunger and food intake. This was initially approved in 2017 to treat Diabetes Type 2 at a dose of 0.25 mg to 1 mg once weekly injections and later as an oral formulation. The same medicine is now approved for obesity at an escalating dose schedule starting from 0.25 mg once weekly and gradually increasing to 2.4 mg once weekly over 16 weeks.

Apart from the convenience of once-weekly dosing, it is better tolerated with fewer GI side effects like nausea, vomiting, diarrhea. Semaglutide’s safety and efficacy were studied in four separate 68 weeks trials called STEP trials. These double-blinded, randomized, placebo-controlled trials with about 2,600 patients treated with Semaglutide Vs 1,500 patients receiving placebo showed a 15% average weight loss in the treatment group. The double-digit weight loss which was usually seen following bariatric surgery was for the first time achieved with medical weight loss. GLP-1 agonists are going to be the game-changer in obesity management and will bring in much-needed new drugs to the often neglected section of metabolic disease, i.e obesity.

Data from the STEP trial demonstrated :

1. About 15% average weight loss in patients treated with Semaglutide along with behavioral intervention.
2. Sugar control and risk for heart disease was dramatically improved in the patients who lost about 10% of body weight with Semaglutide.
3. Obesity like Diabetes is a chronic disease that needs long-term management with medication.
4. Unlike other anti-obesity medications, there was no plateau phase after 28 weeks of treatment. Weight loss with Semaglutide treated arm continued until the end of 68 weeks trial.
5. About one-third of the participants who received Semaglutide lost about 20% of the bodyweight which is almost comparable to that of bariatric surgery.

With the prevalence of overweight/obesity increasing rapidly especially with lifestyle changes imposed upon us by the pandemic, the above data is very promising. There has been a lot of misconceptions about anti-obesity medications even among physicians and with the recall of few medications in the past, there is great skepticism about using them. It is paramount to know the facts about obesity so that it gets the appropriate attention and management like any other chronic illness. So a simple “eat less, work more” will not be sufficient to treat a complex disease with an interplay of genetic, metabolic, psychological, social, and iatrogenic factors. Weight loss experts have been advocating for the long-term use of anti-obesity medications for weight maintenance but until the STEP trials, we did not have data to support it. The FDA approval of Semaglutide for chronic weight management is going to be a turning point in the pharmacotherapy of obesity.