Anne L. Peters, MD
September 05, 2025
This transcript has been edited for clarity.
Today, I’m going to discuss a study that was just published in Diabetes Care by a group of researchers from Israel. Basically, they looked at whether a very slow uptitration of semaglutide was beneficial compared to the on-label, more rapid uptitration of semaglutide.
Now, first off, I love this study because it validates what I’ve been doing for the past 15 years. Starting with liraglutide, I have had patients click up the dose, which means instead of going to where the normal dosing lines are, I have patients listen for clicks. They start at four clicks, then go to eight clicks, and then go to 12 clicks based on their GI (gastrointestinal) side effects and tolerance.
I started doing this about 15 years ago when I spoke to a retired Novo Nordisk employee who had actually worked on the development of this pen, and I asked him whether a click is a dose. He said yes, so I knew that I was getting a stable dose. It was a click, but it was going to be the same when I did it week in, week out.
These investigators took 104 patients with type 2 diabetes and randomized them. Half of them were going to be on the click method, that flexible titration regimen, vs the label-recommended regimen. With the flexible regimen, you’ll get to 1 mg in 16 weeks; with the label-recommended uptitration you get there in half the time, in 8 weeks.
Just to review, the label-recommended titration means you start at 0.25 mg once weekly and do that for 4 weeks, then uptitrate to 0.5 mg for 4 weeks, and finally get to 1 mg. Their use of the click method used five clicks at a time. Five clicks is equal to 0.0675 mg per week so that you get up to that 1-mg dose when you’re at 74 clicks.
The click method lets you basically delay uptitration if you are getting GI side effects. These individuals were allowed to delay for up to 26 weeks. I also have my patients go back down if they reach a dose where they’re not feeling very good and then start uptitrating again. I think these little clicks let people have more control over the up- and down-titration.
The big finding in this study was not only that there were fewer GI side effects, as one would expect with slower titration, but it was in terms of the adherence to using semaglutide. In this study, 19% withdrew in the label-recommended, higher uptitration method vs only 2% with the click method.
I’ve found this over and over again. I can basically take people who’ve tried to take semaglutide using the standard dosing regimen and haven’t tolerated it, and I’ve been able to get them to tolerate it going up at this slower rate. I often don’t get people all the way to 1 mg. If getting to 0.5 mg gets people to their goal, I’ll stay at 0.5 mg.
The other thing I really like about the slow uptitration is that it gives me more time to work on lifestyle. I think, increasingly, we’re recognizing that people should increase their protein intake so they don’t lose as much lean body mass and that they should engage in exercise to maintain their strength and lean body mass.
This way, people lose weight more slowly and they don’t get so gaunt and look so thin. They actually seem to me to be healthier, and hopefully they are healthier because they’re minding their lifestyle and not having the same risk of rapid weight loss with reduction in lean body mass.
My feeling is that this click method with slower titration, certainly for people who are sensitive to the GI side effects of semaglutide, is a really good way to go. If someone seems to tolerate it just fine, you can go up faster. For those people where there are limits to how quickly they can go up, I’d recommend trying this method. It’s now been validated in at least a relatively small pilot study showing that differences between the flexible regimen and the label-recommended approach.
Thank you.
