Older obesity medications including liraglutide remain effective and cost-efficient options even as newer drugs emerge.
≥10% body weight lossA substantial proportion of patients on first-generation obesity medications achieve this clinically meaningful threshold
What the researchers found
First-generation obesity medications — phentermine, orlistat, phentermine/topiramate ER, bupropion/naltrexone SR, and liraglutide 3.0 mg — remain effective and clinically relevant despite the arrival of newer incretin-based therapies. While their average weight loss is lower than next-generation drugs, clinical trial data show that a substantial proportion of patients on these agents achieve 10% or more total body weight loss. The review emphasizes these medications as cost-effective, evidence-based tools for managing obesity-related atherosclerosis and other cardiometabolic complications.
Why it matters
With newer GLP-1 drugs dominating headlines, older obesity medications risk being overlooked — even though they remain affordable, accessible, and effective for many patients. This review reminds clinicians that first-generation agents, including the peptide-based liraglutide, still have a critical role in comprehensive obesity care, especially where cost or access to newer drugs is a barrier.
How the study worked
Narrative review of pharmacologic profiles, clinical trial evidence, and practical considerations for five first-generation obesity medications.
Who was studied
Adults with obesity treated with first-generation anti-obesity medications
What this study cannot tell us
As a narrative review, this paper does not present new clinical data or perform a systematic analysis. Findings are limited to summarizing existing trial evidence without meta-analytic pooling.
How to read the evidence
This is a narrative review summarizing existing clinical trial data. It does not generate new evidence but provides a useful synthesis of established findings.
When this study was published
Published in 2026, this review reflects the current treatment landscape where first-generation agents coexist with newer incretin-based therapies.
The bigger picture
The obesity treatment landscape has expanded rapidly with drugs like semaglutide and tirzepatide, but access remains limited by cost and insurance coverage. First-generation agents — especially liraglutide, the only peptide in this group — fill critical gaps in care and may be used alone or in combination with newer therapies.
Questions still open
- How do first-generation obesity drugs perform in head-to-head comparisons with newer multi-agonists?
- Could combination strategies using older and newer agents improve outcomes while reducing cost?
- What long-term cardiovascular outcomes data exist for patients maintained on first-generation agents?
Common questions
Are older obesity medications still worth using now that newer drugs exist?
Which of these five medications is a peptide drug?
Read the original research
A Review of First-Generation Obesity Medications.
Current atherosclerosis reports, 28(1), 14
Citation
Schmitz, Sarah H; Saunders, Katherine H. (2026). A Review of First-Generation Obesity Medications.. Current atherosclerosis reports, 28(1), 14. https://doi.org/10.1007/s11883-026-01389-0