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Study breakdown

Which Weight Loss Drugs Work Best Over 4 Years? Real-World Veteran Data

CohortModerate evidence
The takeaway

Semaglutide and phentermine/topiramate showed the most consistent long-term weight loss over up to 48 months in a real-world veteran population.

Up to 48 months of data

One of the longest real-world comparisons of weight loss medications, tracking outcomes for up to 4 years

What the researchers found

Semaglutide and phentermine/topiramate showed the most consistent long-term weight loss among veterans, with data extending up to 48 months.

Why it matters

Most weight loss drug studies last 1-2 years. This study provides real-world data on how well these medications work over up to 4 years, which matters because obesity is a chronic condition.

The numbers in context

Weight tracked at 3, 6, 12, 24, 36, and 48 months. Six medications compared: semaglutide, orlistat, liraglutide, phentermine, phentermine/topiramate, and naltrexone/bupropion.

How the study worked

Single-center retrospective study analyzing weight outcomes at multiple timepoints for veterans prescribed various weight loss medications.

Who was studied

U.S. veterans prescribed weight loss medications at Veteran Health Indiana

What this study cannot tell us

Retrospective single-center study without randomization. Patients were not randomly assigned to medications, so differences between groups may reflect patient selection.

How to read the evidence

Rated moderate: long follow-up period provides valuable real-world data, but retrospective single-center design with no randomization limits causal conclusions.

When this study was published

Published in 2024. Builds on a 2021 study from the same center with extended follow-up.

The bigger picture

Most weight loss drug studies last 1–2 years. This 4-year real-world data fills an important gap, showing which medications maintain their effect over the timeframe that actually matters for chronic disease management.

Questions still open

  • Why does phentermine/topiramate perform as well as semaglutide long-term?
  • Would tirzepatide perform even better over 4 years?

Common questions

Which weight loss drug works longest?
In this 4-year real-world study, semaglutide and phentermine/topiramate showed the most sustained results over time.
Do weight loss drugs stop working over time?
Some do — this study found differences between medications in long-term effectiveness, with semaglutide and phentermine/topiramate maintaining benefits best.

Read the original research

Long-Term Assessment of Weight Loss Medications in a Veteran Population.

Federal practitioner : for the health care professionals of the VA, DoD, and PHS, 41(7), 202-207

Citation

Rodriguez, Allison D; Ifeachor, Amanda P; Moore, Emily A; Otte, Cassandra F; Schopper, M Joseph; Liangpunsakul, Suthat; Lteif, Amale A. (2024). Long-Term Assessment of Weight Loss Medications in a Veteran Population.. Federal practitioner : for the health care professionals of the VA, DoD, and PHS, 41(7), 202-207. https://doi.org/10.12788/fp.0490