When people achieve meaningful health benefits and weight loss with weight management medication, the question often arises: Can I reduce my treatment dose? Reasons for wanting to reduce dose are often cost related; others just want to know if they can have the same benefits with less medication. (Note that if the reason is because of side effects, then a dose reduction should be considered until free of side effects.) Most often, when people try reducing the dose, we tend to see some weight regain and some regression of health benefits. We haven’t had any clinical trial data to address this important real-life clinical question – until now.
The SURMOUNT-MAINTAIN study, just published in The Lancet, is the first completed randomized controlled clinical trial designed to evaluate whether weight and health benefits can be maintained if you decrease the dose of GLP1 medication, in this case, the GLP1/GIP receptor agonist tirzepatide (Zepbound/Mounjaro). The study enrolled 441 people to receive tirzepatide for a 60 week weight loss phase. At week 60, 378 people who had completed that phase on tirzepatide 10mg or 15mg (max dose) weekly and had lost at least 5% weight were randomized to continue the same dose of tirzepatide, reduce to 5mg weekly, or switch to placebo for a year.
Before we get into the results, here’s a KEY point to note: starting at 24 weeks after randomization, if 50% of weight lost during the initial phase was regained, participants could receive rescue tirzepatide therapy – meaning that the placebo group would get tirzepatide, and the tirzepatide 5mg group would get a dose increase (a very patient-centric protocol, which is great!).
At the very start of the study, the average baseline BMI was 40.1, and mean baseline weight 113.8kg. The weight loss after the entire 112 week study was -21.9% with high dose (10mg or 15mg) tirzepatide, -16.6% in the group who reduced the dose to 5mg, and -9.9% in the group switched to placebo. However, it’s important to point out that 25% of the tirzepatide 5mg group received rescue therapy (dose increased), and 67% of the placebo group received rescue therapy (tirzepatide started). Improvements in metabolic health were sustained in the group who continued high dose tirzepatide (as expected), while those who reduced to 5mg maintained clinically meaningful benefits to a lesser extent. The placebo group, as expected, experienced regression of weight benefits along with weight regain.
Amongst people who had reached a weight plateau during the weight loss phase, 80% or greater weight reduction was maintained in 77.5% of people treated with ongoing high dose tirzepatide (10mg or 15mg), 42.4% of those treated with low dose tirzepatide 5mg, and 10.4% of those treated with placebo at week 112.
There were no new safety concerns with tirzepatide in this study. The 5mg group appeared to have fewer gastrointestinal side effects, suggesting better tolerability with the lower dose.
BOTTOM LINE: This study shows that after successful weight loss with higher dose tirzepatide (Zepbound/Mounjaro) 10mg or 15mg weekly, reducing the dose (to 5mg) results in some weight regain and some regression of health benefits, confirming what we most often see in clinical practice when dose reduction is attempted. Moving to the lower dose (5mg) is clearly better than stopping treatment entirely. These findings underscore once again that continued treatment is needed for continued health benefit and to keep the weight off.
Disclaimer: I am/have been an investigator in clinical trials of tirzepatide. I receive honoraria as a continuing medical education speaker and consultant from the makers of tirzepatide (Eli Lilly).
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