Lab Notes: Tirzepatide's Weight Maintenance Power and Liraglutide's Role in Diabetes

A groundbreaking phase 3 trial published in JAMA this week demonstrates that continued treatment with tirzepatide (Mounjaro) can maintain and even augment weight loss over 88 weeks. The SURMOUNT-4 study enrolled adults with obesity or overweight (without diabetes) and found that those who stayed on tirzepatide after an initial 36-week lead-in achieved a mean total weight reduction of 25.3% from baseline at week 88. In contrast, those who switched to placebo regained most weight, ending with only 9.9% loss. Key finding: Continuing tirzepatide is essential for long-term weight maintenance. However, readers should note that the study has published corrections—check for updated data. Major conflict of interest: Funded by Eli Lilly, with several authors as employees.

This claim summarizes the overall result from the SURMOUNT-4 trial: Adults with obesity or overweight without diabetes who continued tirzepatide for the entire 88-week study achieved a mean total weight reduction of 25.3% from baseline, compared to 9.9% in those who switched to placebo after 36 weeks. This 15.4 percentage point difference highlights the profound effect of sustained treatment. Key finding: Continuous tirzepatide can reduce body weight by over a quarter of starting weight.

A detailed analysis from the same SURMOUNT-4 trial reveals what happens when treatment is stopped. Patients who switched to placebo after the 36-week lead-in experienced a mean weight regain of 14.0% over the next 52 weeks, while those continuing tirzepatide lost an additional 5.5%. The difference between groups was a striking 19.4 percentage points (95% CI, -21.2% to -17.7%; P<0.001). This underscores that tirzepatide is a treatment, not a cure—weight loss requires ongoing medication. Key finding: Stopping tirzepatide results in significant weight regain, highlighting the need for long-term therapy.

A sobering statistic from the SURMOUNT-4 trial: 83.4% of participants who switched to placebo failed to maintain at least 80% of their initial weight loss at 52 weeks, compared to only 10.5% of those who continued tirzepatide (P<0.001). This means that nearly 9 out of 10 people who stop the drug will not sustain their weight loss. For anyone considering tirzepatide, it's crucial to plan for long-term use. The data also highlight the biological drive to regain weight after significant loss. Key finding: The vast majority of patients regain weight after discontinuing tirzepatide.

The most common adverse events during continued tirzepatide treatment were gastrointestinal—diarrhea (10.7%), nausea (8.1%), and vomiting (5.7%) —mostly mild to moderate. Only 1.8% of patients discontinued due to these effects. This suggests that while side effects are frequent, they are generally manageable with dose adjustments and supportive care. Patients starting tirzepatide should be counseled on GI tolerability and strategies to mitigate symptoms. Key finding: GI side effects are common but rarely lead to discontinuation.

The SCALE Insulin trial evaluated liraglutide 3.0 mg (Saxenda) in overweight or obese adults with type 2 diabetes already on basal insulin. Over 56 weeks, liraglutide led to significantly greater weight loss compared to placebo (approximately 5.4% vs. 2.0%). The drug was well tolerated, with gastrointestinal side effects being common but manageable. However, this study was funded by Novo Nordisk, the manufacturer, and the funder had involvement in study design and analysis—a major conflict of interest to keep in mind. Key finding: Liraglutide can help with weight loss even in patients with insulin-treated diabetes.

A claim from the literature suggests that liraglutide 3.0 mg leads to an average 8% body weight loss in non-diabetic patients with obesity. This is consistent with earlier trials like SCALE Obesity and Prediabetes. In non-diabetics, the drug's effect is more pronounced than in diabetic patients, likely due to the absence of insulin therapy and metabolic issues. However, remember that liraglutide requires daily injections and can cause GI side effects. Key finding: Liraglutide can achieve around 8% weight loss in non-diabetic obese adults.

A sub-analysis of a liraglutide trial focused on the tolerability of nausea and vomiting. The study found that while these side effects are common, they are generally mild and improve over time with dose escalation. Interestingly, the presence of nausea was associated with greater weight loss, possibly due to reduced appetite. Patients who experienced moderate nausea lost more weight than those without. This suggests that while uncomfortable, these symptoms may be a marker of drug efficacy. Key finding: Nausea on liraglutide is linked to better weight loss outcomes, but is usually tolerable. Major conflict of interest: Funded by Novo Nordisk.