A 2014 review identified GLP-1 receptor agonists exenatide and liraglutide as having weight-lowering potential in non-diabetic obese individuals and predicted their role in diabetes prevention — predictions that have since been validated.
Predicted GLP-1 obesity treatment role in 2014When bariatric surgery was the only effective obesity treatment, this review identified GLP-1 drugs' weight-lowering potential and diabetes prevention capability
What the researchers found
Key points from this early review:
- GLP-1 is involved in both peripheral and central satiety pathways
- Clinical trials showed exenatide and liraglutide have weight-lowering potential in non-diabetic obese individuals
- GLP-1 drugs may prevent diabetes development compared to other weight loss agents
- Incretin impairment exists in both obesity and diabetes, potentially linking these two conditions
- At the time of writing (2014), bariatric surgery was the only efficient obesity treatment
- The review predicted GLP-1-based therapies would play a key role in prevention and treatment of both obesity and diabetes
Why it matters
This review was remarkably prescient. Written when GLP-1 drugs were primarily diabetes medications, it correctly predicted their transformation into major obesity treatments and their potential for diabetes prevention. Reading it now provides valuable historical context for the GLP-1 revolution that has since occurred with semaglutide and tirzepatide approvals for obesity.
How the study worked
Narrative literature review of PubMed publications through August 2014, using search terms combining GLP-1, GLP-1 receptor agonists, incretins, obesity, and pre-diabetes. The review covered the biological rationale for GLP-1 therapies and summarized clinical trial evidence for their weight-lowering properties.
What this study cannot tell us
As a 2014 review, it predates the most impactful GLP-1 obesity trials (STEP, SURMOUNT). It covers only exenatide and liraglutide, not newer agents like semaglutide or tirzepatide. The evidence base at the time was limited to relatively small trials in non-diabetic obese populations. The review could not foresee the magnitude of weight loss that higher-dose formulations and dual agonists would achieve.
How to read the evidence
This is a narrative review from 2014 summarizing the limited clinical trial data available at the time. The evidence base has since expanded dramatically with multiple large Phase 3 trials confirming the review's predictions.
When this study was published
Published in 2014, this review predates the major GLP-1 obesity trials (STEP, SURMOUNT). It provides valuable historical perspective on how the field has evolved from early observations to the current GLP-1 treatment revolution.
The bigger picture
This review captures a pivotal moment in GLP-1 drug development history — the transition from viewing these drugs solely as diabetes medications to recognizing their obesity treatment potential. The authors' predictions have been more than validated: semaglutide 2.4 mg now produces 15-17% weight loss, tirzepatide produces over 20%, and GLP-1 drugs have become the biggest pharmaceutical story of the 2020s.
Questions still open
- How have the predictions from this 2014 review been validated by subsequent large-scale obesity trials?
- Has the incretin impairment hypothesis been confirmed as a mechanistic link between obesity and diabetes?
- What further GLP-1 drug developments beyond semaglutide and tirzepatide are on the horizon?
Common questions
When did scientists first realize GLP-1 drugs could treat obesity?
How has GLP-1 obesity treatment changed since 2014?
Read the original research
Therapies for inter-relating diabetes and obesity - GLP-1 and obesity.
Expert opinion on pharmacotherapy, 15(17), 2487-500
Citation
Iepsen, Eva W; Torekov, Signe S; Holst, Jens J. (2014). Therapies for inter-relating diabetes and obesity - GLP-1 and obesity.. Expert opinion on pharmacotherapy, 15(17), 2487-500. https://doi.org/10.1517/14656566.2014.965678