Current and Upcoming Anti-Obesity Drugs: From Semaglutide to Triple Agonists in the Pipeline | Research

The takeaway

Five anti-obesity medications are currently approved for long-term use including liraglutide and semaglutide, with tirzepatide awaiting approval and promising peptide drugs like retartrutide and semaglutide/cagrilintide combination advancing through Phase 3 trials.

5+ next-generation drugs in Phase 3
Beyond the five currently approved anti-obesity medications, at least five next-generation peptide-based drugs — including dual and triple gut hormone agonists and oral GLP-1 formulations — are in Phase 3 trials, promising an unprecedented expansion of treatment options.

What the researchers found

The review identifies the current approved anti-obesity medications and their successors:

**Currently approved (long-term):** Orlistat, naltrexone/bupropion, phentermine/topiramate, liraglutide (GLP-1 RA), semaglutide (GLP-1 RA)

**Awaiting approval:** Tirzepatide (dual GLP-1/GIP agonist)

**In Phase 3 trials:** Semaglutide/cagrilintide combination (GLP-1 + amylin analog), oral semaglutide for obesity, orforglipron (oral non-peptide GLP-1 agonist), BI 456906, retartrutide (triple GLP-1/GIP/glucagon agonist)

The Korean KSSO guidelines recommend pharmacotherapy for adults with BMI ≥25 kg/m² who haven't responded to non-pharmacological treatments, emphasizing personalized drug selection based on individual patient characteristics.

Why it matters

The obesity drug landscape is undergoing its most rapid transformation in history. This review provides a comprehensive snapshot of where we stand — from established drugs to next-generation peptide-based therapies that may produce weight loss approaching what bariatric surgery achieves. Understanding this pipeline is essential for clinicians making treatment decisions and for patients navigating their options.

How the study worked

This is a narrative review of approved anti-obesity medications and drugs in Phase 3 clinical trials, structured around the 2022 Korean Society for the Study of Obesity (KSSO) clinical guidelines. The authors review evidence from major clinical trials for each drug and discuss the evolving treatment landscape.

What this study cannot tell us

The review focuses primarily on the Korean context (KSSO guidelines with BMI ≥25 threshold), which may not directly apply to other populations where different BMI thresholds are used. As a 2023 publication, some of the pipeline drugs discussed have since had trial results released or regulatory decisions made. Long-term safety data is limited for newer agents, and cost/access issues are acknowledged but not deeply addressed.

How to read the evidence

This is a narrative review structured around clinical practice guidelines (KSSO 2022). The underlying evidence for approved drugs includes large-scale randomized controlled trials, while pipeline drugs are supported by Phase 2-3 trial data of varying maturity.

When this study was published

Published in 2023, this review captures the drug pipeline at a time of rapid advancement. Several drugs discussed (particularly tirzepatide) have since received regulatory approvals, and Phase 3 results for others (retartrutide, orforglipron) have been reported. The landscape continues to evolve quickly.

The bigger picture

This review captures a watershed moment in obesity medicine. The field has shifted from a handful of modestly effective drugs to a rich pipeline of peptide-based therapies that target multiple gut hormone pathways simultaneously. The progression from single-target GLP-1 agonists (liraglutide) to dual agonists (tirzepatide) to triple agonists (retartrutide) reflects a growing understanding that obesity involves multiple hormonal systems, and the most effective treatments may need to address several simultaneously.

Questions still open

Will triple agonists like retartrutide ultimately replace single and dual agonists, or will different patients need different approaches?
Can oral GLP-1 formulations (orforglipron, oral semaglutide) achieve equivalent weight loss to injectable versions, making treatment more accessible?
How will healthcare systems handle the massive cost burden of prescribing anti-obesity medications to the estimated 50% of the population who may qualify?

Common questions

What are the most effective weight loss drugs currently available?

As of this review, semaglutide (Wegovy) is the most effective single-agent anti-obesity medication, producing approximately 15-17% total body weight loss. Tirzepatide (which was awaiting approval at the time but has since been approved) produces even greater weight loss of approximately 20-25%. Both are injectable peptide-based drugs that target gut hormone pathways.

What are triple agonists and why are they exciting?

Triple agonists like retartrutide target three gut hormone receptors simultaneously: GLP-1, GIP, and glucagon. Each receptor contributes to weight loss through different mechanisms — appetite suppression, energy expenditure, and fat breakdown. By hitting all three pathways at once, triple agonists may produce weight loss comparable to bariatric surgery in some patients. Early trial data has been very promising, showing weight loss exceeding what any single or dual agonist achieves.

Read the original research

Approved Anti-Obesity Medications in 2022 KSSO Guidelines and the Promise of Phase 3 Clinical Trials: Anti-Obesity Drugs in the Sky and on the Horizon.

Journal of obesity & metabolic syndrome, 32(2), 106-120

View on PubMed ↗Publisher’s paper ↗

Citation

Jeon, Eonju; Lee, Ki Young; Kim, Kyoung-Kon. (2023). Approved Anti-Obesity Medications in 2022 KSSO Guidelines and the Promise of Phase 3 Clinical Trials: Anti-Obesity Drugs in the Sky and on the Horizon.. Journal of obesity & metabolic syndrome, 32(2), 106-120. https://doi.org/10.7570/jomes23032