Outcomes Following Discontinuation of Semaglutide

This blog describes the study on what happened after semaglutide was discontinued in the SELECT 1 trial. The SELECT 1 trial was the landmark study that demonstrated the efficacy of semaglutide to treat overweight/obesity in participants who did not have diabetes. 

Here are the key points of each study:

SELECT 1 Trial: 

• 1961 participants

• 74% were female

• 75% were white

• 94% completed the trial

• Weight loss at 68 weeks was 15.9% on average

• On average, weight loss started right away and was about 10% at 6 months

• While average weight loss was about 15%, weight loss did vary. 

• Like many weight loss interventions, there were “quartiles” of responders. 

• About ⅓ were “super responders” 

• About 15% didn't lose much at all

• About ⅓ lost about 10% 

• Nearly 50% lost less than 15% starting weight

In the SELECT 1 Trial Extension, after 68 weeks, all treatment was discontinued, including semaglutide and lifestyle interventions was discontinued and 327 participants were followed for another year (52 weeks).  The participants were mostly white (76%) and women (66%) with an average age of 48 years. The weight loss in the participants who were followed was 17.3% when the medication was discontinued and 2% in the placebo group. One year later, participants had regained two-thirds of the weight they had lost with similar changes in cardiometabolic risk factors. 

This first graph shows the total group’s weight change trends. It shows that while the average weight loss was 17.2% when the semaglutide was discontinued, after a year off the medication, there weight was 5.2% below where it started in the first place. But, like there were groups of people who lost more than others, since everyone gained back about two-thirds of the weight they lost, those who lost more, even after they had regained, their weight was about 12% below where it had started. Interestingly, this is exactly what is seen in the Very Low Calorie Diet / Protein Sparing Modified Fast. Weight loss is much more than with other diet protocols, and even though weight regain occurs, since more weight was lost in the first place, the end weight is still significant and more than with other dietary interventions.  So, the second graph shows what happens to the weight curves based on the groups of weight loss. 

So, this is the data on what happens in the year after semaglutide is discontinued.  Longitudinal healthcare is important on an individual basis for durable outcomes. This medication has been in clinical use for about three years now. So, there is much to learn about how to have successful outcomes long term in real world use. Remember, this is a marathon, not a sprint. 

Take Back Your Long-Term Plan,

Valerie Hope-Slocum Sutherland, MD

References:

https://pubmed.ncbi.nlm.nih.gov/33567185/

Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10. PMID: 33567185.

https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.14725

Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, Lingvay I, McGowan BM, Oral TK, Rosenstock J, Wadden TA, Wharton S, Yokote K, Kushner RF; STEP 1 Study Group. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022 Aug;24(8):1553-1564. doi: 10.1111/dom.14725. Epub 2022 May 19. PMID: 35441470; PMCID: PMC9542252.