Comprehensive Guide to Current and Upcoming Hormone-Based Weight Loss Drugs Including GLP-1 Agonists and Beyond | Research

The takeaway

A comprehensive review of hormone-based anti-obesity medications finds that dual and triple receptor agonists (tirzepatide, retatrutide) can achieve up to 22% weight loss, far exceeding single-target GLP-1 drugs.

22.1% weight loss
Achieved by retatrutide (GLP-1/GCG/GIP tri-agonist) in 48 weeks — the most effective hormone-based anti-obesity drug reported to date

What the researchers found

The evolution from single-target GLP-1 drugs to dual and triple receptor agonists is producing dramatically greater weight loss: tirzepatide (GIP/GLP-1) achieves 17.8% and retatrutide (GLP-1/GCG/GIP tri-agonist) achieves 22.1% placebo-subtracted weight reduction.

Why it matters

Obesity affects over a billion people globally. The rapid advancement from single-target to multi-target hormone therapies is producing progressively greater weight loss, potentially approaching the efficacy of bariatric surgery with a medication-only approach.

The numbers in context

Two GLP-1RAs are frontrunners. Triple agonists like retatrutide represent the next wave.

How the study worked

Narrative review of approved and emerging hormone-based anti-obesity medications, covering published clinical trial data for GLP-1RAs, dual and triple agonists, and amylin receptor agonists.

Who was studied

Review of obesity drug development landscape

What this study cannot tell us

Review article — no new data generated. Long-term safety data for newer agents (tirzepatide, retatrutide) is limited. Cardiovascular outcome data is available primarily for semaglutide. Cost and access remain significant barriers to widespread use.

How to read the evidence

Review of mixed evidence strength — strong for approved drugs (liraglutide, semaglutide), moderate for tirzepatide, and preliminary for pipeline agents (retatrutide, oral GLP-1 drugs).

When this study was published

Published in 2024. Captures the state of the rapidly evolving obesity drug landscape.

The bigger picture

The obesity treatment landscape is undergoing a revolution driven by peptide-based therapeutics. Each generation of drugs achieves greater weight loss by targeting additional gut-brain hormone pathways. The long-term safety and cardiovascular benefits of newer agents remain to be established, but the trajectory suggests obesity may become a highly treatable condition.

Questions still open

Will triple agonists like retatrutide maintain their dramatic weight loss efficacy in larger phase III trials?
What are the long-term cardiovascular and safety profiles of dual and triple receptor agonists?
How will the availability of oral GLP-1 drugs change prescribing patterns and patient access?

Common questions

What are the most effective weight loss drugs available now?

Currently approved hormone-based options include injectable semaglutide (~15% weight loss) and tirzepatide (~17.8% weight loss). Liraglutide is also available but less effective. Several more potent options, including oral GLP-1 drugs and triple agonists, are in clinical trials.

What is retatrutide and when might it be available?

Retatrutide is a triple agonist that targets GLP-1, glucagon, and GIP receptors simultaneously, achieving up to 22.1% weight loss in a phase II trial. It's still in clinical development and likely several years from potential approval.

Read the original research

Approved and Emerging Hormone-Based Anti-Obesity Medications: A Review Article.

Indian journal of endocrinology and metabolism, 28(5), 445-460

View on PubMed ↗Publisher’s paper ↗

Citation

Sidrak, Wael R; Kalra, Sanjay; Kalhan, Atul. (2024). Approved and Emerging Hormone-Based Anti-Obesity Medications: A Review Article.. Indian journal of endocrinology and metabolism, 28(5), 445-460. https://doi.org/10.4103/ijem.ijem_442_23