Obesity continues to rise worldwide, bringing with it a cascade of health risks. The issue is not simply extra weight but the biological effects of excess fat; which fuels low-grade inflammation, strains the heart,  and increases the risk for diabetes,  stroke,  and heart disease⁽¹⁾.

Even modest weight loss of around 3 to 5% of body weight can improve cholesterol, blood pressure, and blood sugar.

For those with more severe obesity, losing 5 to 15% can make a greater impact. Yet the most difficult part of any weight loss effort is rarely the diet itself, it’s maintaining the results once the initial pounds are gone⁽²⁾.

The Illusion of “Mission Accomplished”...Why Weight Returns

When weight is lost, the body resists change. It burns fewer calories, hunger hormones surge, and appetite increases⁽³⁾. This is a built-in survival mechanism that assisted our ancestors endure famine. In modern life, however it works against long-term weight maintenance. Without a structured plan, most people gradually regain much of what they’ve lost⁽⁴⁾.

Exercise and Medication: Two Different Tools

Exercise remains one of the most effective defenses against weight regain. It boosts metabolism, preserves lean muscle (which helps sustain calorie burn), and strengthens the cardiovascular system.

A newer approach uses medication.

Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, mimics a natural hormone that signals fullness and helps control appetite. Studies have shown that it can help people maintain weight loss for at least a year.

Researchers wanted to understand which approach (i.e.,  exercise,  medication,  or both) offers the most lasting benefits, and whether any of these strategies also protect heart and vascular health⁽⁵⁾.

The First Study: One Year After Weight Loss

In a randomized clinical trial, adults with obesity but without diabetes began an eight-week low-calorie diet, losing an average of 12 percent of their body weight, which is roughly 27lbs for someone starting at 225 pounds.

They were then assigned to one of four groups for the next year:

• Exercise only: Moderate to vigorous training, mainly cycling and running.
• Liraglutide only: Daily 3.0 mg injections with usual activity.
• Combination: Exercise plus liraglutide.
• Placebo: No active treatment beyond general lifestyle advice.

Key Findings

• All three active treatment groups maintained their weight loss, while those receiving placebo regained about half of what they had lost.
• The combination of exercise and liraglutide performed best, as participants lost additional weight, averaging a 16% total reduction from baseline, which is about twice the effect of either treatment alone⁽⁵⁾.
• Exercise helped preserve lean muscle and improve cardiorespiratory fitness.
• Liraglutide primarily reduced appetite and maintained fat loss.
• Together, they improved insulin sensitivity, blood sugar control,  emotional well-being,  and overall cardiovascular fitness.

Liraglutide alone slightly increased heart rate, a potential side effect,  but this effect disappeared when paired with exercise.

Figure: Changes in Body Weight and Body-Fat Percentage during the Trial.
Shown are the mean changes in body weight (primary end point; Panel A) and body-fat percentage (secondary end point; Panel B) during a low-calorie diet (weeks −8 to 0,  shaded area) and during 1 year of subsequent treatment (from randomization [week 0] to week 52). Panel C shows a bar chart of the percentages of participants in each trial group who had a total weight loss from baseline at enrollment (week −8) to the end of the trial (week 52) of at least 5%,  10%,  15%,  and 20% of the initial body weight (left graph) and also shows a box plot of the percentage weight loss from baseline (dashed line) to the end of the trial in each group (right graph). In the box plot,  the diamonds indicate means; the black horizontal bars medians; the tops and bottoms of the boxes the upper and lower quartiles,  respectively; and the whiskers ±1.5 times the interquartile range or the smallest or highest observation. Dots indicate individual observations⁽⁵⁾.

The Follow-Up Study: Effects on the Arteries

The same research group later examined whether these strategies also influenced atherosclerosis, the gradual buildup of plaque in arteries that underlies most cardiovascular disease.

They measured blood markers of inflammation, such as interleukin-6 (IL-6) and interferon-gamma (IFN-γ), and indicators of blood vessel health,  including vascular cell adhesion molecules (VCAM-1 and ICAM-1). Ultrasound imaging assessed carotid intima-media thickness (cIMT),  a standard measure of arterial wall thickening and early atherosclerosis⁽⁶⁾.

What They Found

After one year of weight maintenance⁽⁶⁾:

• Exercise,  but not liraglutide,  reduced inflammation and slowed artery thickening.
• Participants who exercised had lower levels of IL-6 and IFN-γ and healthier blood vessel markers.
• Ultrasound scans showed thinner arterial walls,  suggesting slower progression of atherosclerosis.
• Liraglutide maintained weight loss but did not significantly improve vascular inflammation or structure.

What It Means

Both exercise and liraglutide helped people sustain their weight loss, but only exercise provided direct protection for the heart and blood vessels. These findings highlight that not all methods of weight maintenance have the same impact on long-term health.

Liraglutide helps stabilize appetite and maintain weight, but exercise acts more broadly, it strengthens the cardiovascular system, reduces inflammation,  and improves the body’s metabolic flexibility. In essence, medication helps you stay lighter, but exercise helps you stay healthier.

The Takeaway

Together,  the two studies show that:

• Weight loss jump-starts health improvements.
• Liraglutide helps maintain those losses by reducing hunger.
• Exercise not only maintains weight but also protects the heart,  blood vessels,  and emotional well-being.
• The combination offers the greatest overall benefit.

Yet if one goal must take priority, particularly for heart health, the evidence is clear, exercise remains the cornerstone of lasting health after weight loss.

This data adds to a growing body of evidence underscoring that while GLP-1s are powerful tools, they don’t replace the benefits of regular physical activity for long-term heart and vascular health. 

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References: 
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    2.    Logue J,  Thompson L,  Romanes F,  et al: Management of obesity: summary of SIGN guideline. Bmj 340:c154,  2010
    3.    Iepsen EW,  Lundgren J,  Holst JJ,  et al: Successful weight loss maintenance includes long-term increased meal responses of GLP-1 and PYY3-36. Eur J Endocrinol 174:775-84,  2016
    4.    Wing RR,  Bolin P,  Brancati FL,  et al: Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 369:145-54,  2013
    5.    Lundgren JR,  Janus C,  Jensen SBK,  et al: Healthy Weight Loss Maintenance with Exercise,  Liraglutide,  or Both Combined. N Engl J Med 384:1719-1730,  2021
    6.    Sandsdal R: Weight loss maintenance with exercise but not with GLP-1 receptor agonist treatment decreases atherosclerosis development. Presented at the European Association for the Study of Diabetes annual meeting,  Vienna,  Austria,  2025