Sustained Midlife Weight Loss Linked With Long-Term Health Benefits

New data show that sustained midlife weight reduction, which was achieved without surgical or pharmacological interventions, increases long-term health benefits beyond just associations with diabetes. The findings, published in JAMA Network Open, also demonstrated a decrease in all-cause mortality.¹

The data show a decrease in all-cause mortality for sustained midlife weight loss achieved without surgical or pharmacological interventions. | Image Credit: Kittiphan - stock.adobe.com

Both tirzepatide (Mounjaro, Zepbound) and semaglutide (Ozempic, Wegovy) have shown weight loss benefits as well as benefits for the treatment of diabetes, cardiovascular disease, and sleep apnea. When comparing glucagon-like peptide-1 (GLP-1) receptor agonists, including tirzepatide, semaglutide, and liraglutide (Victoza, Saxenda), tirzepatide demonstrated more weight loss and antihypertensive benefits across all anti-obesity medications studied.²

“[GLP-1s] being approved for weight loss came about a year after this explosion where there was a trend on a lot of social media sites, particularly TikTok, where people were coming to the realization these were really effective for weight management,” Luke Turnock, PhD, MSc, said in an interview.³ “As this awareness of these drugs got everywhere, we then saw a rise in advertising.”

At Asembia’s AXS25 Summit, the GLP-1 market was highlighted due to its unprecedented growth, which is projected to double in the next decade. The medication class, which has been around since 2005, has seen growth in markets beyond diabetes, including obesity, chronic kidney disease, and cardiovascular health. Only Saxenda, Wegovy, and Zepbound are indicated for weight loss, with CVS Caremark announcing Wegovy as the preferred GLP-1 medication for weight loss on their formularies and pushing Zepbound out of the formulary.^4,5

In the current study, investigators aimed to determine the association between reduction in body mass index without surgical or pharmacological treatment and long-term incidence of chronic diseases and all-cause mortality, specifically for patients aged 40 to 50 years. Data included clinical examination and electronic health records from 1991 and 2013. There were 23,149 patients included across 3 cohorts. In the first cohort, 2161 patients maintained a healthy weight from the first to second evaluations, 96 lost weight, 565 gained weight, and 1296 had persistent overweight. For the second cohort, 750 individuals maintained a healthy weight, 188 lost weight, 170 became overweight, and 1227 had persistent overweight.¹

At the first examinations, the differences in smoking, blood pressure, total cholesterol, and postload glucose for individuals with weight loss and those with persistent overweight were small, but at the second evaluation, the blood pressure and total cholesterol were lower for the weight loss group, according to the study authors. At the end of follow-up, cohort one saw 29.3% of patients with healthy weight, 26.1% with midlife weight loss, 36.1% with weight gain, and 45.2% were persistently overweight and developed at least 1 chronic condition.¹

In a median follow-up of 22.8 years, individuals in the first cohort who had persistent healthy weight, weight loss, and weight gain had a decreased risk of first chronic disease compared with patients with persistent overweight, and the pattern was similar for the second cohort, which was used for mortality risk, according to the study authors.¹

Pharmacists have the opportunity to support patients and counsel them on diet and exercise for weight loss, including with the use of GLP-1 medication.

“I always start with discussing this medication as a tool. This medication as a tool has great data to promote weight loss and obesity and some other disease states, but the other tools in your arsenal are diet. So, giving the patient some counseling about diet, if you have time discussing things like the plate method or other specific diets that are appropriate for their specific disease states, that'll be very patient specific,” Lydia Newsom, PharmD, clinical associate professor of pharmacy practice at Mercer University College of Pharmacy, said in an interview.⁶ “The other tool in your arsenal, or another tool, would be physical activity. Encouraging the patient to support and to choose some specific exercises or physical activity that work for their lifestyle is really important.”

READ MORE: Obesity Management Resource Center

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REFERENCES

1. Strandberg TE, Strandberg AY, Jyväkorpi S, et al. Weight Loss in Midlife, Chronic Disease Incidence, and All-Cause Mortality During Extended Follow-Up. JAMA Netw Open. 2025;8(5):e2511825. doi:10.1001/jamanetworkopen.2025.11825

2. Gallagher A. Tirzepatide Facilitates Greater Weight Loss, Strongest Antihypertensive Effects. Drug Topics. February 13, 2024. Accessed May 28, 2025. https://www.drugtopics.com/view/tirzepatide-facilitates-greater-weight-loss-strongest-antihypertensive-effects

3. Nowosielski B, Turnock L. Q&A: Expert on Social Media’s Normalization of Lifestyle Drugs. Drug Topics. April 18, 2025. Accessed May 28, 2025. https://www.drugtopics.com/view/expert-on-social-media-s-normalization-of-lifestyle-drugs

4. Gallagher A. Projection Estimates GLP-1 Market to Nearly Double by End of Decade | Asembia 2025. Drug Topics. May 1, 2025. Accessed May 28, 2025. https://www.drugtopics.com/view/projection-estimates-glp-1-market-to-nearly-double-by-end-of-decade-asembia-2025

5. Nowosielski B. CVS Caremark Makes Wegovy Preferred Weight-Loss Medication. Drug Topics. May 2, 2025. Accessed May 28, 2025. https://www.drugtopics.com/view/cvs-caremark-makes-wegovy-preferred-weight-loss-medication

6. Meara K, Newsom L. Q&A: Pharmacists’ Role in GLP-1 Diet, Exercise Counseling. Drug Topics. March 21, 2025. Accessed May 29, 2025. https://www.drugtopics.com/view/q-a-pharmacists-role-in-glp-1-diet-exercise-counseling