Some people have sent messages asking about changing from semaglutide to tirzepatide following the “news” article that came out “comparing” Wegovy to Zepbound for weight
loss. I am so grateful to have these important conversations and engage with people on their treatment options, so I wanted to take this opportunity to “flesh out” my thoughts.
THOUGHT ONE
This study was not a “head to head” trial between the medications. To compare two treatments, that is technically supposed to be in a “head to head” study in which one study randomizes two groups of people to the two treatments and has a control group all within the same study. The statistical analyses include looking at the characteristics of the groups to see if there are any differences between the groups receiving the different treatments. The two groups receiving the different treatment options have the other factors “controlled” for, so it is as close as possible to just comparing the treatments. Wegovy and Zepbound have never been compared in a head to head study. They were each compared to lifestyle modification alone in separate studies. So, there is no analysis to say if the groups taking the medications were the same or different and no controls for any other factors. So, it is technically not completely valid to use them to compare the results. That being said, it is important to acknowledge that tirzepatide has a dual mechanism of action compared to a single mechanism, and so probably does have “more” weight loss for “some” people.
THOUGHT TWO
This is not news. Whomever prescribed your medication “should” have known this when they engaged with you in shared decision making. They should have already taken this into account and there should be a reason why you are on the treatment you are on. In my experience it is most commonly because of insurance or cost. Unfortunately, whenever a new medication comes out for an old indication, insurance companies rarely cover the newest, most expensive medication unless a person has tried and failed the old one, although that is not always the case. When paying out of pocket, tirzepatide costs about twice as much as semaglutide, whether you are getting the compounded or the brand name version. It ranges $400-$550 a month in my experience as opposed to $200-$300 a month. The second most common reason is that a person is already doing well on the older medication. Remember, these weight loss numbers are averages, and half the people lose less and half the people lose more. There is variation (see thought three below for more on this). So, if someone has lost 22% of their body weight on Wegovy and they are feeling great, there is not much reason to think they will lose more than that by switching to Zepbound, and they can go backwards in the transition.
THOUGHT THREE – THE MOST IMPORTANT ONE
In all treatments for obesity, there is a WIDE RANGE of efficacy among different people for ANY treatment. If you read my blog from last week, you saw the graph that showed on semaglutide, while the average weight loss was about 15%, there was a wide range of weight loss. There were “quartiles” of weight loss, which is actually a phenomenon observed pretty consistently for all weight loss treatments. This means that instead of everyone losing about the same amount of weight on treatments for obesity, there tends to be about 4 groups of responders: a small group for whom it does not seem to work very well at all, a group of “super responders” for whom it works really, really well, and two groups in between that span the average. This has been found for several weight management medications and interventions, and you probably have heard about it for people who have had some weight loss surgeries as well. Why is that? Well, like many things with obesity, there is no accepted reason yet. But I think it is because there are so many different factors potentially at play that there is a LOT of variation between individuals, and a single treatment may not be addressing all the crucial factors in an individual. Meaning, a weight loss surgery or medication may work great in one person, and not so well in another because there is some other physiologic condition going on. It may be sleep apnea, a vitamin deficiency, sarcopenia, a weight positive medication, another hormonal cause, higher insulin resistance, sarcopenia, and probably a whole lot of other things we have not researched before. This is why it is crucial to have an initial comprehensive medical evaluation in the context of your entire health that takes into account your blood work, medications, weight history, body composition, and any other relevant factors, and then to have your body’s response to treatment routinely reassessed along the way and compared to the results in the studies to see if you are on track to reach the health outcomes needed for you. And, if not, to re-evaluate potential reasons why not and address those or change or add to your treatment. And, if there is nothing sepcific to point to and say "aha!", I think that is where the word "practice" comes into play in medicine. Sometimes, your care provider just has to use their epxerience, training and clinical judgement and make a call. This is what I am doing when I have you meet with me for “refills”. I am thinking and reassessing and projecting out into the future and seeing if everything is on track or if we need to change course. This is when I am thankful for the 10 years of observations since June 2015. The medications have changed, but there are actually a lot of commonalities in the body’s response to treatment between bariatric surgery very low calorie diets/protein sparing modified fasts and now these medications. There was even a lecture at the recent Obesity Week conference by The Obesity Society in San Antonio (where I presented a poster on outcomes from Rainier Medical- thank you!) which was entitled – lessons from Very Low Calorie Diets for highly effective anti obesity medications.
HOW DO I CHOOSE?
The MOST IMPORTANT THING about a weight management medication is that it is safe, effective, and YOU CAN STAY ON IT AND KEEP TAKING IT AS LONG AS YOU NEED TO. So, if you are paying $550 a month and cannot keep doing that for the foreseeable future, there is an 85% chance the weight you lose will come back and weight cycling is worse than not losing the weight in the first place because then people tend to get sarcopenic with obesity and there is no treatment for that. So, how do I tend to “choose” when making a recommendation to a patient between treatment options? Of course, there are always individual factors, but, in general:
Phentermine/Topiramate- actually can cause 27% weight loss in some people which is “as much” as the average in tirzepatide. These are pills taken twice a day typically that cost about $10 a month and the side effects tend to be energy, dry mouth and constipation (there are others in the fine print, of course)
Semagltutide versus Tirzepatide- they are very similar insofar as weekly injections with similar side effect profile of nausea, bowel movement changes, and perhaps fatigue. So, in counseling between them, I tend to say:
- If you are not already one and you can get either one just fine (i.e. price does not matter or both are covered), then take the tirzepatide. It probably causes more weight loss and less nausea.
- If you are on semaglutide and you have GI side effects and you can get tirzepatide, then try that one. You may feel better.
- If you are on semaglutide and your weight loss is not what is expected (based on objective criteria, not just expectations), and your provider has checked that there is not some major or apparent other cause (because if that is missed, then changing medications may be pointless), and you can get tirzepatide AND STAY ON IT, then it may make sense to switch.
We are only about 3 years “in” on using these medications to seriously treat obesity. As we know from bariatric surgery, some people lose more weight than others, some people lose too much weight, some people experience weight recurrence, some people lose a lot of muscle and get fragility fractures from osteoporosis, and some people do great for a time and then get hungry again. There are probably going to be many similarities between surgery patients and patients treated with these medications, I think. Already, we see some people feeling like “food noise” starts to increase again after a period on one of these medications. Even though the weight stays off, the food noise is cumbersome. There is some evidence of the “satiety” decreasing, even when the weight is not coming back. If you are doing fine on one medication, is it better to keep the next medication in your “back pocket” and be strategic with timing? Will it be like sleep medications, where sleep medications stop working after a while and people have to “cycle” through them? So far, the weight loss is durable on semaglutide for over 3 years, which is the longest data we have- on average. That is reassuring.
So, in summary, while medications are improving, don’t just hop to the latest and greatest medication. But be sure to have that option considered also if your current outcome is not meeting goals. So, it is important, but not simple. This study was about averages, and you are an individual. So, use it to have a conversation about your individual treatment, but not as the sole reason to change treatments. Be sure to consult with a provider trained and education in obesity medicine. It is great there is more access to treatment for obesity. We need less barriers and more ease of access. But there are a lot of “pop up” sources and transparency is key. But, if you want to have an in-depth discussion, there are different levels of training, education, expertise and tools that used in the comprehensive and longitudinal treatment of the complex condition of overweight/obesity. The Obesity Medicine Association has a “provider finder” option to locate one near you and it shows if they are “Board Certified” in obesity medicine which is a secondary certification, so it requires a primary certification. You can see if it is Family Medicine or Internal Medicine or some other specialty. Transparency is key in choosing your healthcare provider.
Soon, we may have a triple agonist out – retatutride- and we will have more to consider! Thank you for reading!
Take Back Your Incretin Hormones,
Valerie Hope-Slocum Sutherland, MD
Diplomate, American Board of Internal Medicine, 2005 to present
Diplomate, American Board of Obesity Medicine, 2015 to present
Thanks for sharing this information. Between Mounjaro, Ozempic, Wegovy, Zepbound, and Retatutride it can make one’s head swim.
Then throw in Phentermine/Topiramate, Lorcaserin (Belviq), Orlistat (Xenical), and Phentermine … yikes! Thank goodness we have you to keep up with all of this, because most of the rest of us certainly cannot.