Introduction: Semaglutide (Wegovy®) is FDA approved for weight loss. It has been so popular due to the drug’s effectiveness that the manufacturer has been unable to consistently keep up with rising demand. Advocates have proposed that this drug be used as a lifelong treatment to treat obesity, at the current cost of nearly $20,000 a year. Considering the high cost of the drug, as well as the ongoing shortages, we proposed a novel method to make this weight loss drug available to more people with less cost and complexity.
Methods: Individuals employed with a medical practice who were overweight or obese and wanted to lose weight were recruited. Lunchtime meals were supplied four days a week based on a Mediterranean diet. Study medication (semaglutide) was given weekly at a dose that mimics the commercial drug that was not available at the time of the study. After three months of weekly semaglutide injections, subjects were switched to metformin and continued the free lunches as previously described. Body weight was measured, and BMI was calculated.
Individuals were allowed to take a second course of semaglutide if needed, but only after a 2 month “washout” period to reduce tolerance to the drug. They were followed an average of 11 months.
Results: As previously reported, the subjects lost an average of 23.4 lbs (range 21-28 lbs) at four months. This translates into 10-14% body weight loss. After discontinuation of the original semaglutide treatment, patients were followed several more months, and achieved long term weight loss without the need for continued weekly doses of semaglutide. Range was an additional loss of 45 lbs (in an individual who lost 20 lbs in the first 4 months) to a gain of 5 lbs (in and individual who lost 28 lbs in the first 4 months)
Conclusions: All subjects completed one round of semaglutide treatment (average of 13 weeks) and none needed to do a full second round of treatment to maintain weight loss for approximately one year. Metformin was used by some to aid in weight maintenance, and some used occasional doses of semaglutide for effective long term weight loss. This program has been a very effective and much less expensive option than weekly, life time injectable drug therapy.Range of total weight loss at 11 months was 15lbs (to an ideal body weight for this individual) to 73 lbs (previously obese individual) with none of the subjects requiring a second full round of semaglutide treatment.
Introduction.
Semaglutide was originally FDA approved for type II diabetes. It can be used as a daily oral pill, or a weekly subcutaneous shot.The mechanism of action is well described elsewhere, and generally works through GLP-1 (glucagon like peptide) agonistic actions. The target organs appear to be the brain, gastrointestinal tract, and the pancreas.
This class of drug improves effectiveness of insulin pathways through a variety of mechanisms, as well as decreasing appetite through mechanisms that are not yet fully understood. Recently, semaglutide was found to reduce unrelated undesirable habitual activities such as shopping addiction and excess alcohol intake.
This drug is generally safe and well tolerated. Studies have linked the use of semaglutide in diabetics to a reduction in cardiovascular events and cardiovascular risk factors.
The weight loss associated with semaglutide was not entirely unexpected, but much more robust than could have been reasonably anticipated. This has led to the FDA approval of semaglutide for weight loss in certain individuals.
Long term studies have shown substantial weight loss with semaglutide vs placebo. A follow up study where a group of individuals were instructed to stop the semaglutide (or placebo) after a year and a quarter demonstrated a varying degree of weight gain. This has led to the notion of using this very expensive (and effective) drug for years, if not forever.
However, in the study to demonstrate weight gain after cessation of semaglutide needs to be considered within the design of the study. Individuals who were on the drug or placebo were instructed to also reduce calorie intake by 500kcal per day, as well as to exercise 150 minutes a week.
In the drug discontinuation arm of the study, individuals were instructed to stop the injections (drug or placebo) and resume their old unhealthy habits. To restate: during the weight loss intervention, the participants were to take the semaglutide (or placebo), diet and exercise. During the drug discontinuation arm of the study, the participants were instructed to stop dieting, stop exercising and stop the injections.
As can be expected, when the participants discontinued the injections and resumed a higher calorie diet and a less active lifestyle, many gained the weight back. Notably, those on placebo generally gained all the weight back and then some. Those with the most weight loss kept about ½ of the weight off at one year. Those with an average weight loss (about 16% of body weight) gained almost one half of the weight back after one year of discontinuation of injections, diet and exercise as can be expected.
We proposed to answer the question “can short term use of semaglutide coupled with lifestyle efforts lead to long term weight loss if they make some effort to keep it off?”
Methods:
This has been previously described for the first 4 months of treatment. After the initial 13 weeks of semaglutide, subjects were offered oral daily metformin (850 mg at night) to enhance the effect of weight loss effectiveness. They were also allowed to use additional low dose semaglutide on an as needed basis.
There was no placebo arm, and the use of metformin or semaglutide was not controlled, but at the discretion of the patient and their medical provider.
Results:
One subject exited the observation due to pregnancy. The remaining subjects maintained the weightloss with the exception of one individual gaining 5 lbs after a 21 lb weight loss. She attributed this to gain of muscle mass by intentionally gaining strength through weight training, and maintained a healthy BMI of 23. Another individual lost a total of 28 lbs during the 13 weeks of semaglutide, and a total of 73 lbs in the 11 months which included 2 months of metformin.
In the 11 months of follow up, one individual used 6 weekly doses of semaglutide to help control appetite, and most used some degree of metformin to curb appetite and control weight gain.
Conclusion:
Semaglutide is an effective medication for weight loss. The popular assumption that the drug must be taken forever to maintain weight loss is based on a clinical trial designed to prove that if an individual resumes unhealthy eating and activity, along with cessation of a weight loss drug, some of the weight will come back.
In this observation, we asked the individuals to discontinue the semaglutide after 13 weeks, and also asked them to try to continue a healthy (and newly learned) lifestyle habit of reduced portion size and Mediterranean diet. Metformin and occasional semaglutide was offered for assistance as needed.
We have found through this study as well as our experience with over 1,000 patients in a private practice that individuals can make substantial lifestyle behavior changes in as little as 13 weeks that can lead to long term weight loss goals.
Semaglutide was designed to be a drug for weight loss to be taken for a lifetime. There is a rapid tolerance to the drug and the long term maintenance dose is 10 times as strong as the beginning weight loss dose. Metformin improves the levels of GLP-1 which is the target of semaglutide and appears to aid in long term weight loss after cessation of semaglutide.
The recent evidence showing not only weight loss, but also better control of habits with semaglutide, combined with a novel program of lifestyle changes, episodic semaglutide injections, and metformin.
In this review, the employer paid for the semaglutide as well as healthy meals for the employees. It can be expected that a healthier workforce would lead to lower health insurance costs, as well as more employee retention leading to a win-win situation for employer and employee.
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