Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition?

In the paper

“In the context of a body weight reduction of 14.9% (À15.3 kg) and fat reduction of 24.7% (À10.4 kg), individuals also lost an average of 13.9% of their total LM (À6.9 kg) (17).”

What the sources say

• Partly supported

  The Abstract reports 14.9% (15.3 kg) mean weight loss at week 68 with semaglutide. “Change in Body Composition” reports reduced fat and lean mass in a 140-participant DXA subpopulation, but our copy does not give the claimed 24.7% (10.4 kg) or 13.9% (6.9 kg) reductions. The full trial enrolled 1,961 participants, not 140. (LLM, conf=0.88)

  cites [17] Wilding, 2021, Once-weekly semaglutide in adults with overweight or obesity, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“A study of 23 older individuals (71 years) observed that, after 18 weeks, RT increased knee extensor maximal torque by 41.7% in men and 15.8% in women.Differences in muscle quality were also reported, whereby muscle quality increased by 33.7% in males compared with 8.8% in females (63).”

What the sources say

• Supported

  Methods > Participants reports 23 volunteers with a mean age of 71.3 years. Results > Muscle strength and functional abilities gives the 18-week maximal-torque increases of 41.7% in men and 15.8% in women; Results > Muscle cross-sectional area, fat/water ratio, and quality gives the muscle-quality increases of 33.7% and 8.8%, respectively. No page numbers are available in our copy. (LLM, conf=0.94)

  cites [63] Da Boit, 2016, Sex differences in the response to resistance exercise training in older people, Physiol Rep source

In the paper

“Both cognitive restraint and moderate to vigorous physical activity were associated with less weight regain.”

What the sources say

• Supported

  The Results section, under “Increased cognitive restraint and moderate-to-vigorous intensity physical activity are associated with maintained weight loss,” explicitly reports that increases in both were associated with less weight regain during weight maintenance. Table 5 reports the corresponding negative associations with percentage change in body weight. (LLM, conf=0.95)

  cites [78] Jensen, 2022, Exploratory analysis of eating- and physical activity-related outcomes from a randomized controlled trial for weight loss maintenance with exercise and liraglutide single or combination treatment, Nat Commun source

In the paper

“As discussed above, Sema administration is associated with an LM loss of 13.9% ($6.9 kg) over a period of 68 weeks (17), while Tz induced a 10.9% (6 kg) loss over 72 weeks of therapy (20).”

What the sources say

• Partly supported

  The Change in Body Composition section (page unavailable) reports that lean body mass decreased in absolute terms in the semaglutide DXA subpopulation. Our copy does not give the claimed 13.9% or 6.9 kg lean-mass loss, although it confirms the trial’s 68-week duration. The tirzepatide result is attached to a different citation and is not assessed here. (LLM, conf=0.88)

  cites [17] Wilding, 2021, Once-weekly semaglutide in adults with overweight or obesity, N Engl J Med sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [20] Jastreboff, 2022, Tirzepatide once weekly for the treatment of obesity, N Engl J Med source

In the paper

“The exercise group increased LM by 3.4% (12.1 kg) compared with the Lira group (0.0 kg; 95% CI À1.0 to 1.1), while the combination group also exhibited an increase of 0.8% (10.5 kg).”

What the sources say

• Partly supported

  The Metabolic Health-Related End Points section (page not supplied) reports increased lean mass with exercise, and the Discussion (page not supplied) says the combination preserved lean mass. Our copy does not give the claimed 3.4%, 2.1 kg, 0.8%, or 0.5 kg changes, or the liraglutide group's 0.0 kg estimate and confidence interval; preservation alone does not establish an increase in the combination group. (LLM, conf=0.82)

  cites [77] Lundgren, 2021, Healthy weight loss maintenance with exercise, liraglutide, or both combined, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“Studies indicate that, from the third to fourth decade onwards, aging is accompanied by loss of strength of around 2.5-4.0%per year (73), with leg strength declining despite habitual endurance exercise in active older adults (74).”

What the sources say

• Partly supported

  The Function section reports that strength declines with advancing age at an average rate of 2–4% per year, supporting the approximate rate. It does not establish that this rate begins in the third or fourth decade; the early-onset ages discussed in the Size section concern muscle mass, not strength. The endurance-exercise clause has a separate citation and is not assessed here. No page numbers were supplied for these passages. (LLM, conf=0.86)

  cites [73] Mitchell, 2012, Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative review, Front Physiol sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [74] Marcell, 2014, Leg strength declines with advancing age despite habitual endurance exercise in active older adults, J Strength Cond Res source

In the paper

“A study comparing the independent and combined effects of caloric restriction and exercise in 107 elderly (70 years) individuals with obesity reported that, after 12 months, the exercise group increased LM by 2.3% (11.3 kg), while the dietplus-exercise and diet-only groups experienced decreases in LM of 3.1% (À1.8 kg) and 5.2% (À3.2 kg).”

What the sources say

• Partly supported

  The Results section (Body Weight and Composition; page unavailable) reports the stated directions and kilogram changes in lean mass for all three groups, and the Methods describe a one-year trial of 107 older adults with obesity. However, the citing sentence as printed says the exercise group gained 11.3 kg, whereas the source reports 1.3 kg. The supplied paraphrase corrects that figure. (LLM, conf=0.88)

  cites [70] Villareal, 2011, Weight loss, exercise, or both and physical function in obese older adults, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“After a 36-week lead-in involving Tz treatment (10 mg or 15 mg), which induced weight reduction of 20.9% (À22.1 kg), individuals were randomized to continued Tz treatment for another 52 weeks (additional weight reduction of 5.5% or À4.7 kg, totaling À25.8%, or À26.8 kg, over the 88-week treatment period) or placebo injections (regaining 54.5%, or 12 kg, of the total body weight loss during the 36-”

What the sources say

• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [83] Aronne, 2024, Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial, JAMA sourceExperimental — accuracy not yet measured

In the paper

“After 12 months, greater weight loss was observed in the combination group (Lira 1 exercise, 3.5% or À3.4 kg) than the Lira-only group (0.7% or À0.7 kg).The exercise-only group increased body weight by 2% (12.0 kg).”

What the sources say

• Supported

  The Body Weight and Body-Fat Percentage section reports a further 3.4-kg loss in the combination group. Its reported placebo gain of 6.1 kg and treatment differences imply a 0.7-kg loss with liraglutide alone and a 2.0-kg gain with exercise alone, consistent with the claim’s rounded percentages. The combination–liraglutide difference was not statistically significant (P=0.13), but the claim describes observed losses rather than claiming significance. (LLM, conf=0.87)

  cites [77] Lundgren, 2021, Healthy weight loss maintenance with exercise, liraglutide, or both combined, N Engl J Med source

In the paper

“After an initial 8-week period of caloric restriction during which participants with obesity lost an average of 12% ($13 kg) of their initial body weight, 5.1 kg LM, and 7.3 kg fat mass, this study randomized 195 participants (42 ± 12 years) to four groups: placebo, exercise (combined training), Lira alone, or Lira 1 exercise (Fig. 5).”

What the sources say

• Partly supported

  The Low-Calorie Diet section reports a mean weight loss of 13.1 kg (12%) over eight weeks. Table 1 shows lower fat and lean mass after the diet, but its before-and-after groups differ in size (215 versus 195), and it does not report mean losses of 7.3 kg fat mass or 5.1 kg lean mass. Those exact figures are not verified by our copy. (LLM, conf=0.88)

  cites [77] Lundgren, 2021, Healthy weight loss maintenance with exercise, liraglutide, or both combined, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“Better results in the combined group were also found in terms of fat loss, with a reduction of 3.5% (À4.7 kg), approximately twice the decrease in the exercise group (À1.8% or À1.4 kg) and the Lira group (À1.6% or À2.0 kg) (77).”

What the sources say

• Partly supported

  The Body Weight and Body-Fat Percentage section reports a greater reduction in body-fat percentage with the combination than with either treatment alone, and the Discussion says fat-mass loss was approximately twice that of the single treatments. Our copy does not report the cited group-specific figures of 3.5%, 1.8%, and 1.6%, or the corresponding kilogram losses; its reported percentage-point figures are treatment comparisons, not those values. (LLM, conf=0.86)

  cites [77] Lundgren, 2021, Healthy weight loss maintenance with exercise, liraglutide, or both combined, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“an initial 20-week Sema (2.4 mg) administration reduced body weight by 10.6% (À11.1 kg) (82).Thereafter, an additional body weight reduction of 7.9% (À7.1 kg) was reported for those maintained on Sema treatment until 68 weeks, whereas the group that discontinued treatment at 20 weeks demonstrated body weight regain of 6.9% (6.1 kg) (82).”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [82] Rubino, 2021, Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial, JAMA source

In the paper

“An overview of 12 systematic reviews and meta-analyses summarizing the impact of exercise training (with or without diet) on body composition during weight loss reported significant weight (À1.5 to 3.5 kg) and fat mass (À1.3 to 2.6 kg) losses in response to exercise training (68) but no net increase in LM.However, RT reduced the loss in LM by 0.8 kg in comparison with diet only.”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [68] Bellicha, 2021, Effect of exercise training on weight loss, body composition changes, and weight maintenance in adults with overweight or obesity: an overview of 12 systematic reviews and 149 studies, Obes Rev source

In the paper

“muscle mass is highly metabolically active, with muscle loss linked to decreased metabolic rate (84).”

What the sources say

• Supported

  The “Lean mass preservation” section describes lean mass as metabolically active and reports that resting energy expenditure falls by approximately 13 kcal/day for each kilogram of muscle lost. The “Targeting energy expenditure” section also attributes approximately 20% of resting energy expenditure to skeletal muscle. (LLM, conf=0.92)

  cites [84] Christoffersen, 2022, Beyond appetite regulation: targeting energy expenditure, fat oxidation, and lean mass preservation for sustainable weight loss, Obesity (Silver Spring) source

In the paper

“It was not designed to evaluate the effects of combining exercise and incretin treatment as the primary weight loss therapy.It is also relevant that the exercise intervention involved ET rather than RT and that Sema and Tz have much”

What the sources say

• Supported

  The Methods state that participants first completed an 8-week low-calorie diet and were then assigned to exercise, liraglutide, both, or placebo for a year; the Discussion describes the trial as studying weight-loss maintenance, not the combination as primary weight-loss therapy. The Interventions section describes a predominantly aerobic program of cycling, running, and brisk walking. It also included brief circuit training in supervised sessions, so “rather than resistance training” describes the program’s emphasis, not an absolute exclusion. (LLM, conf=0.92)

  cites [77] Lundgren, 2021, Healthy weight loss maintenance with exercise, liraglutide, or both combined, N Engl J Med source

In the paper

“Another systematic review and meta-analysis, which summarized six articles regarding the impact of RT on diet-induced loss in LM mass, concluded that adding RT to diet attenuated the loss of LM by 93.5%, with an absolute difference in LM of approximately 1 kg.Similar reductions in fat mass and body weight were reported between RT-with-diet and diet-alone groups (69) (Fig. 4).”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [69] Sardeli, 2018, Resistance training prevents muscle loss induced by caloric restriction in obese elderly individuals: a systematic review and meta-analysis, Nutrients source

In the paper

“a recent report indicated that, in middle-aged (49 ± 12 years) individuals with obesity (BMI $30 kg/m 2 ) (81), 68 weeks of Sema therapy induced mean weight loss of 17.3% (À18.3 kg) vs. 2% (À2.1 kg) for placebo, but 52 weeks after therapy, participants had regained 67% (112.2 kg) of their lost weight.”

What the sources say

• Supported

  The Results (section 3.2) report mean weight loss of 17.3% with semaglutide versus 2.0% with placebo over 68 weeks, followed by regain of 11.6 percentage points in the semaglutide arm. The Discussion (section 4) describes this as regaining a mean of two-thirds of prior weight loss during the one-year extension. The kilogram figures are approximate conversions consistent with the reported mean baseline weight of 105.5 kg; the treatment also included lifestyle intervention. (LLM, conf=0.87)

  cites [81] Wilding, 2022, Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension, Diabetes Obes Metab source

In the paper

“However, it is germane that while the weight loss is primarily fat, a considerable amount is lean or muscle mass.”

In the paper

“Liraglutide and semaglutide (GLP-1RA), tirzepatide (GLP-1 and GIP receptor dual agonist), and retatrutide (GLP-1, GIP, and glucagon receptor triple agonist) are peptides with incretin agonist activity that induce $ $ $ $15-24% weight loss in adults with overweight and obesity, alongside beneficial impacts on blood pressure, cholesterol, blood glucose, and insulin.”

In the paper

“Studies indicate that supervised resistance exercise training interventions with a duration >10 weeks can elicit large increases in lean mass ($ $ $ $3 kg) and strength ($ $ $ $25%) in men and women.”

In the paper

“Maintaining muscle mass and function as humans age is crucial to avoiding sarcopenia and frailty, which are strongly linked to morbidity and mortality.”

In the paper

“However, these agents also cause rapid and significant loss of lean mass ($ $ $ $10% or $ $ $ $6 kg), comparable to a decade or more of aging.”

In the paper

“Glucagon-like peptide 1 receptor agonists (GLP-1RA) induce substantial weight loss in randomized trials, effects that may be enhanced in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists.”

In the paper

“Incretin therapies induce significant weight loss, part of which is lean mass ($10% or $6 kg), comparable to a decade or more of aging.”

In the paper

“This suggests that compensation for LM loss is effective using RT, but overcompensation (i.e., increase in mass rather than prevention of loss) does not typically occur.”

In the paper

“Based on well-established effects on LM in obesity, sarcopenia, and type 2 diabetes, it is plausible that RT would mitigate LM loss, and perhaps promote greater fat mass loss, in participants administered incretin therapy.”

In the paper

“In 94 premenopausal women (35 ± 6.2 years) who were overweight (BMI 27-30 kg/m 2 ), after 1 year of dietary intervention, RT improved fat-free mass (10.3 kg, or 0.6%), whereas ET (À1.0 kg or À2.2%) and no exercise training (À1.5 kg or À3.1%) reduced fat-free mass (61).”

What the sources say

• ?Not checked — no full text of the sourcecites [61] Hunter, 2008, Resistance training conserves fat-free mass and resting energy expenditure following weight loss, Obesity (Silver Spring) source

In the paper

“The absolute magnitude of RT impact in terms of LM mitigation depends upon factors such as whether the exercise is combined with protein supplementation or whether the LM loss is induced by diet ($1-kg effect) or disease (>1-kg effect).”

In the paper

“In healthy untrained men (n = 38, age 37 ± 7 years), the cross-sectional area of the quadriceps femoris increased by 6% after 21 weeks of RT, while endurance training (ET) (e.g., cycling) induced a modest increase of 2% (56).”

What the sources say

• ?Not checked — no full text of the sourcecites [56] Mikkola, 2012, Neuromuscular and cardiovascular adaptations during concurrent strength and endurance training in untrained men, Int J Sports Med source

In the paper

“an RT study of individuals ($70 years) with presarcopenia (based on appendicular LM index) observed no significant differences between males and females in LM but that only males significantly improved their strength (64).”

What the sources say

• ?Not checked — no full text of the sourcecites [64] Vikberg, 2019, Effects of resistance training on functional strength and muscle mass in 70-year-old individuals with pre-sarcopenia: a randomized controlled trial, J Am Med Dir Assoc source

In the paper

“we propose that RT may be a key intervention that, when performed in conjunction with incretin treatment, could improve body composition and provide additional health benefits.”

In the paper

“Collectively, this evidence supports RT as an effective approach to increase or maintain LM or at least mitigate the decrease of LM associated with diet interventions.”

In the paper

“Larger improvements in LM have been reported after RT in younger (11.7 kg, 95% CI 1.0-2.4kg) compared with older adults (10.9 kg, 95% CI 0.8-1.1 kg), although both groups benefited (62).”

What the sources say

• ?Not checked — no full text of the sourcecites [62] Lopez, 2022, Moderators of resistance training effects in overweight and obese adults: a systematic review and meta-analysis, Med Sci Sports Exerc source

In the paper

“While incretin pharmacotherapies are very effective for inducing weight loss, extensive diet literature indicates that weight is rapidly regained on cessation of energy intake restriction (80).This also appears to be true of incretin therapies.”

What the sources say

• ?Not checked — no full text of the sourcecites [80] Machado, 2022, Understanding weight regain after a nutritional weight loss intervention: systematic review and meta-analysis, Clin Nutr ESPEN source