Why exercise is essential for restoring fitness after GLP-1-based weight loss

By Vijay Kumar MalesuReviewed by Susha Cheriyedath, M.Sc.Jan 26 2026

New trial evidence shows that without structured exercise, weight loss medications may leave physical fitness unchanged, highlighting movement as the key to real functional recovery.

Study: Physical Fitness with Exercise and GLP-1 Receptor Agonist Treatment Alone or Combined After Diet-Induced Weight Loss: A Secondary Analysis of a Randomized Controlled Trial in Adults with Obesity. Image Credit: Towfiqu ahamed barbhuiya / Shutterstock

In a recent study published in the journal Sports Medicine, a group of researchers evaluated how structured exercise and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy, alone or combined, influence physical fitness during long-term weight maintenance following diet-induced weight loss.

Obesity, Fitness, and the Limits of Weight Loss Alone

More than 650 million adults worldwide live with obesity, a condition strongly linked to reduced mobility, lower cardiorespiratory fitness, and poorer quality of life. Even after losing excess weight with medication or diets, people may still struggle with daily activities such as walking briskly or climbing stairs. This raises an important question, does weight loss alone lead to meaningful improvements in physical fitness.

Currently, multiple medications are used to treat obesity, including GLP-1 RAs. Previous research suggests that a substantial proportion of weight loss during pharmacotherapy may consist of fat-free mass, which has raised concerns about long-term physical function and independence. It is therefore important to understand how structured exercise interacts with weight-loss medications to improve functional health, not merely reduce body weight.

Study Design and Participant Selection

This exploratory secondary analysis was conducted within a randomized, placebo-controlled clinical trial involving adults aged 18 to 65 years with obesity, defined as a body mass index between 32 and 43 kg per square meter, and without diabetes mellitus. All participants first completed an eight-week, approximately 800-kilocalorie-per-day low-calorie diet. Only those achieving at least a 5% reduction in body weight were eligible for randomization.

Intervention Groups and Treatment Allocation

The 52-week randomized intervention allocated participants to four groups. One group received placebo with usual physical activity; the second received placebo plus structured exercise; the third received liraglutide, a GLP-1 RA, with usual physical activity; and the fourth received liraglutide combined with structured exercise. Liraglutide was administered at 3.0 mg per day with stepwise dose escalation based on tolerability.

Structured Exercise Program and Fitness Assessment

The structured exercise program aimed to meet World Health Organization physical activity recommendations and included supervised group-based interval cycling and circuit training, alongside individually performed moderate-to-vigorous activity. Exercise intensity was objectively monitored using heart rate devices.

Physical fitness was assessed at baseline, after the low-calorie diet, and after 52 weeks. Outcomes included stair-climb performance, cardiorespiratory fitness measured as peak oxygen consumption (VO₂peak), and muscle strength assessed as maximal isometric knee extensor torque. Linear mixed-effects models were used to compare changes between groups.

Participant Adherence and Exercise Volume

A total of 193 participants were randomized, and approximately 85% completed the 52-week intervention. Participants assigned to exercise completed a median of 2.65 sessions per week, corresponding to approximately 108 minutes of moderate-to-vigorous physical activity weekly. Exercise levels were similar between participants receiving liraglutide and those receiving placebo, indicating that GLP-1 RA treatment did not reduce exercise participation.

Effects on Physical Function and Mobility

Physical functional performance improved most clearly in groups that included exercise. Participants in the combined exercise and liraglutide group completed the stair-climb test significantly faster than those receiving liraglutide alone or placebo, reflecting meaningful improvements in mobility and lower-limb function.

Exercise alone produced comparable improvements, whereas liraglutide alone did not improve stair-climb performance despite sustained weight loss.

Cardiorespiratory Fitness Outcomes

Cardiorespiratory fitness, assessed as VO₂peak relative to fat-free mass, increased by approximately 10% in the exercise and combined treatment groups. In contrast, liraglutide alone did not produce a statistically significant improvement in this fitness measure compared with placebo.

Exercise also improved absolute VO₂peak and maximal cycling power, reinforcing its role in enhancing cardiovascular capacity.

Muscle Strength and Muscle Quality

Muscle strength, measured as maximal knee extensor torque, remained stable across all groups, indicating that neither exercise nor liraglutide caused a decline in absolute strength.

Strength relative to body weight improved in all active treatment groups, reflecting weight reduction with preserved muscle function. Muscle quality declined in the placebo group, while it was maintained in participants who exercised or received liraglutide.

Dose, Response Relationship Between Exercise and Fitness

Further analyses showed that greater volumes of moderate-to-vigorous exercise were associated with superior functional outcomes. Each additional 10 minutes of weekly exercise was linked to faster stair-climb performance and higher VO₂peak relative to fat-free mass, demonstrating that even modest increases in physical activity yield measurable benefits beyond those achieved during the initial low-calorie diet phase.

Implications for Long-Term Obesity Management

This study demonstrates that structured moderate-to-vigorous exercise is the primary driver of improvements in physical fitness during long-term weight maintenance, even when weight loss is supported by GLP-1 RA therapy.

While GLP-1 RAs are effective for sustaining weight loss, they do not appear to significantly improve physical fitness outcomes in the absence of exercise. In contrast, structured exercise, alone or combined with pharmacotherapy, leads to clinically meaningful gains in mobility, cardiorespiratory fitness, and functional independence.

These findings highlight the importance of combining weight-loss medications with structured exercise programs to optimize functional health outcomes in adults with obesity, rather than focusing on weight reduction alone.