Canybec Sulayman
December 15, 2024

A Comprehensive Review: GLP-1s and Weight Management in 2024 and Lean Mass Loss Comparison (Semaglutide vs Tirzepitide)

The new meta-analysis reveals impressive results for both semaglutide and tirzepatide in non-diabetic patients with obesity

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Weight Loss Efficacy Findings

According to the new systematic review and meta-analysis by Müllertz et al. (2024), both semaglutide and tirzepatide demonstrate significant efficacy in non-diabetic patients with obesity:

Semaglutide (2.4mg weekly):
  • Average weight loss: -12.9% vs placebo (Müllertz et al., 2024)
  • Waist circumference reduction: -9.7cm
  • Supporting data from STEP trials (Wilding et al., 2021; Garvey et al., 2022)

Tirzepatide (10/15mg weekly):
  • Average weight loss: -19.2% vs placebo (Müllertz et al., 2024)
  • Waist circumference reduction: -14.6cm
  • Corroborated by SURMOUNT trials (Jastreboff et al., 2022; Wadden et al., 2023)

Body Composition Analysis

Key findings from subpopulation analyses in the STEP 1 and SURMOUNT-1 trials revealed:

  • Semaglutide: ~39% of total weight loss from lean mass (Wilding et al., 2021)
  • Tirzepatide: Total fat mass reduced by 34%, lean mass by 11% (Jastreboff et al., 2022)

Clinical Implications

Safety Profile (Müllertz et al., 2024):
  • Semaglutide: 91% experienced at least one adverse event
  • Tirzepatide: 81.5% experienced at least one adverse event
  • Predominantly gastrointestinal side effects, diminishing after initial titration

Long-term Considerations:
  • Weight regain of approximately two-thirds after discontinuation (Wilding et al., 2022)
  • Exercise combination shows superior outcomes in lean mass preservation (Lundgren et al., 2021)
  • Cardiovascular benefits now established (Lincoff et al., 2023)

Future Directions

Current research developments include:

  • Higher dose semaglutide (7.2mg) in STEP UP trial (Clinical Trials ID: NCT05646706)
  • Oral semaglutide showing 15.1% weight loss (Knop et al., 2023)
  • CagriSema combination therapy development (Enebo et al., 2021)

Clinical Practice Recommendations

Based on the current evidence:

  1. Initiate treatment in appropriate BMI categories (≥30 or ≥27 with comorbidities) (Müllertz et al., 2024)
  2. Implement concurrent exercise program (Lundgren et al., 2021)
  3. Monitor closely during titration for side effect management (Müllertz et al., 2024)
  4. Counsel on long-term treatment necessity (Wilding et al., 2022)

This comprehensive meta-analysis represents a significant advancement in our understanding of medical weight management options, with efficacy approaching bariatric surgery results (Sjöström et al., 2007). However, success requires an integrated approach combining pharmacotherapy with lifestyle modifications and careful monitoring.

References

Enebo, L. B., Berthelsen, K. K., Kankam, M., et al. (2021). Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet, 397(10286), 1736-1748.

Garvey, W. T., Batterham, R. L., Bhatta, M., et al. (2022). Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine, 28(10), 2083-2091.

Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., et al. (2022). Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine, 387(3), 205-216.

Knop, F. K., Aroda, V. R., do Vale, R. D., et al. (2023). Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 402(10403), 705-719.

Lincoff, A. M., Brown-Frandsen, K., Colhoun, H. M., et al. (2023). Semaglutide and cardiovascular outcomes in obesity without diabetes. New England Journal of Medicine, 389(24), 2221-2232.

Lundgren, J. R., Janus, C., Jensen, S. B. K., et al. (2021). Healthy weight loss maintenance with exercise, liraglutide, or both combined. New England Journal of Medicine, 384(18), 1719-1730.

Müllertz, A. L. O., Sandsdal, R. M., Jensen, S. B. K., & Torekov, S. S. (2024). Potent incretin-based therapy for obesity: A systematic review and meta-analysis of the efficacy of semaglutide and tirzepatide on body weight and waist circumference, and safety. Obesity Reviews, 25(5), e13717.

Sjöström, L., Narbro, K., Sjöström, C. D., et al. (2007). Effects of bariatric surgery on mortality in Swedish obese subjects. New England Journal of Medicine, 357(8), 741-752.

Wadden, T. A., Chao, A. M., Machineni, S., et al. (2023). Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nature Medicine, 29(11), 2909-2918.

Wilding, J. P. H., Batterham, R. L., Calanna, S., et al. (2021). Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine, 384(11), 989-1002.

Wilding, J. P. H., Batterham, R. L., Davies, M., et al. (2022). Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes, Obesity and Metabolism, 24(8), 1553-1564.