What happens to cardiometabolic risk when you stop tirzepatide?
The short answer is that your cardiometabolic risk factors worsen again, and the degree of worsening directly tracks with how much weight you regain. A post-hoc analysis of the SURMOUNT-4 trial followed 308 adults with obesity who had lost at least 10% of their body weight on tirzepatide over 36 weeks, then were switched to placebo for 52 weeks [1]. The researchers grouped participants by how much of their lost weight they regained: less than 25%, 25% to less than 50%, 50% to less than 75%, or 75% or more. Across every cardiometabolic measure—waist circumference, systolic blood pressure, non-HDL cholesterol, hemoglobin A1c, and fasting insulin—the more weight a person regained, the more their initial improvements reversed. For instance, systolic blood pressure rose by 6.8 mmHg in the group that regained the least weight, but by 10.4 mmHg in the group that regained the most [1]. This tells you that the benefits are not locked in; they depend on keeping the weight off.
Can tirzepatide improve cardiometabolic risk through other mechanisms besides weight loss?
Yes, there is evidence that tirzepatide can improve some risk factors through pathways other than weight loss—specifically by improving sleep apnea. The SURMOUNT-OSA trials studied people with moderate-to-severe obstructive sleep apnea (OSA) and obesity [2][3]. In these trials, tirzepatide significantly reduced blood pressure, inflammation (hsCRP), triglycerides, and insulin resistance compared to placebo. A mediation analysis then asked: how much of these improvements was due to weight loss alone, and how much was due to improvements in sleep apnea (measured by the apnea-hypopnea index and sleep apnea-specific hypoxic burden)? The results showed that improvements in OSA metrics independently mediated reductions in hsCRP, HOMA-IR (a measure of insulin resistance), and triglycerides—meaning some of the cardiometabolic benefit came from treating the sleep disorder itself, not just from losing weight [2][3]. However, this independent effect was limited to those specific measures; for systolic blood pressure, weight loss was the dominant driver, and for diastolic blood pressure, neither weight nor OSA improvements fully explained the benefit [3].
Does the evidence support withdrawing tirzepatide to improve cardiometabolic risk?
No, the evidence strongly argues against withdrawing tirzepatide if your goal is to improve or maintain cardiometabolic health. The SURMOUNT-4 data is clear: stopping the drug leads to weight regain in the vast majority of people, and that regain erases the cardiometabolic gains [1]. The SURMOUNT-OSA data adds a nuance: even though tirzepatide can improve some risk factors through sleep apnea improvements independent of weight, those improvements happen while you are on the drug, not after you stop [2][3]. There is no evidence that withdrawing tirzepatide itself confers any cardiometabolic benefit. In fact, the authors of the SURMOUNT-4 analysis explicitly state that their findings "underscore the importance of continued obesity treatment" [1]. So, if you are considering stopping tirzepatide, the evidence suggests you should expect your cardiometabolic risk factors to worsen in step with any weight you regain.
About These Sources
This answer is built on 3 peer-reviewed studies — published from 2025 to 2026, 3 from 2024 or later, 2 in Q1 journals — selected as the most relevant from 3 studies that passed quality screening, drawn from 39 papers retrieved from a database of over 500 million.
Sources used in this answer
Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity
In a post-hoc analysis of the SURMOUNT-4 trial (308 participants), withdrawing tirzepatide led to weight regain in most participants, and the degree of cardiometabolic parameter worsening (e.g., systolic blood pressure rose by 6.8 to 10.4 mmHg, HbA1c by 0.14% to 0.35%) directly correlated with the amount of weight regained, with those regaining less than 25% of lost weight showing no significant worsening in waist circumference, non-HDL cholesterol, or fasting insulin.
Effect of tirzepatide on OSA-related cardiometabolic risk measures in SURMOUNT-OSA
In the SURMOUNT-OSA trials (Study 1, n=234; Study 2, n=235), tirzepatide significantly improved multiple cardiometabolic risk measures (e.g., systolic blood pressure by -7.9 mmHg, hsCRP by -28.9%, triglycerides by -32.2% in Study 1), and mediation analysis showed that improvements in sleep apnea metrics independently mediated changes in hsCRP, HOMA-IR, and triglycerides, while weight loss alone mediated systolic blood pressure changes.
Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial
In the same SURMOUNT-OSA trials, a separate analysis confirmed that tirzepatide treatment was associated with greater alleviation of cardiometabolic risk factors than placebo, with independent mediation by OSA metrics on hsCRP, HOMA-IR, and triglycerides, and by the combination of weight and OSA metrics on non-HDL cholesterol; no significant mediation by weight or OSA was found for diastolic blood pressure.