GLP-1 Pipeline: What’s Coming

Pipeline Overview Table

Important: All drugs listed below are investigational and not yet approved by the FDA or any regulatory agency (except where noted). Clinical trial results are preliminary and may change. Scroll horizontally on mobile.

Drug	Key Results	Timeline	Why It Matters
Retatrutide Eli Lilly Phase 3	Triple-hormone agonist (GLP-1 + GIP + glucagon). Phase 3 TRIUMPH-4: 28.7% weight loss at 68 weeks — highest of any obesity trial to date. Also improved cholesterol, inflammation markers, and blood pressure [1] [2].	Multiple Phase 3 trials underway; FDA submission possible 2026–2027 [3]	First drug to target three hormones at once. The added glucagon pathway burns more calories and fat than current two-pathway drugs. Could become the most effective weight-loss medication ever approved.
Orforglipron Eli Lilly Phase 3	Oral pill — no injection needed. ACHIEVE-1: HbA1c reduction of 1.3–1.6%, weight loss ~7.9% at 40 weeks. Beat oral semaglutide (Rybelsus) head-to-head [5] [6].	Seven Phase 3 trials ongoing; FDA filing potential in 2026 [5]	A pill you swallow — no needles, no fasting restrictions. Simpler to manufacture than injectable peptides, so potentially cheaper and more accessible worldwide.
CagriSema Novo Nordisk Phase 3	Semaglutide + amylin analogue combined. REDEFINE trials: ~22.7% weight loss at 68 weeks. REIMAGINE 2: outperformed Ozempic alone in both weight loss (14.2%) and blood sugar control [7] [8].	Filed for obesity approval. T2D filing to follow [8]	Adds a second appetite-suppressing hormone (amylin) to proven semaglutide. Novo Nordisk's planned successor to Wegovy — designed to produce more weight loss than Ozempic/Wegovy alone.
Survodutide Boehringer Ingelheim Phase 3	Dual GLP-1 + glucagon agonist. Phase 2: up to ~19% weight loss at 46 weeks. Received FDA Breakthrough Therapy designation for fatty liver disease (MASH) [9] [10].	Phase 3 results expected 2026 [10]	The glucagon component helps the body burn stored fat in the liver — making this especially promising for people with both obesity and fatty liver disease (MASH).
Pemvidutide Altimmune Phase 2b	Dual GLP-1 + glucagon agonist. IMPACT trial: fatty liver disease (MASH) resolved in 59% of patients vs 19% on placebo. Weight loss ~6.2% at 24 weeks. Extremely low dropout rate (<1%) [11] [12].	Phase 3 planning underway [13]	Stands out for remarkably few side effects — almost nobody quit the trial due to adverse reactions. Could be the best-tolerated option for people who struggle with GI side effects from other GLP-1 drugs.
Amycretin Novo Nordisk Phase 2	Oral dual GLP-1 + amylin pill. Phase 2: up to ~14.5% weight loss plus significant blood sugar reduction [14] [15].	Pivotal trials being planned; earliest approval possible late 2028+ [16]	Combines CagriSema's two-hormone approach into a single daily pill — no injections. Novo's long-term answer to Lilly's orforglipron, but with dual pathways instead of one.
Danuglipron Pfizer Discontinued	Oral GLP-1 pill — development stopped. Twice-daily version had too many dropouts from nausea. Once-daily version halted after a patient developed potential liver injury [18].	Discontinued [18]	A cautionary tale — making an oral GLP-1 pill is extremely hard. Pfizer spent years and billions before pulling the plug. Shows why Lilly's orforglipron success is so significant.

Understanding the Pipeline Landscape

The Multi-Agonist Trend

Current approved GLP-1 drugs activate one receptor (GLP-1) or two (GLP-1 + GIP, in the case of tirzepatide). The pipeline is moving toward drugs that activate three or more hormonal pathways simultaneously. The rationale: different hormones affect appetite, metabolism, and energy expenditure through distinct mechanisms, and combining them may produce additive or synergistic effects.

GLP-1 alone primarily reduces appetite and slows gastric emptying
Adding GIP (as tirzepatide does) appears to enhance insulin sensitivity and may improve tolerability
Adding glucagon (as retatrutide, survodutide, and pemvidutide do) increases energy expenditure and drives hepatic fat reduction — particularly relevant for liver disease
Adding amylin (as CagriSema and amycretin do) provides complementary satiety signaling through different brain pathways

The Race for Oral Formulations

Current GLP-1 options are predominantly injectable. Rybelsus (oral semaglutide) exists but requires strict fasting protocols and produces less weight loss than injections. The pipeline reflects a push toward oral formulations without these limitations:

Orforglipron (Lilly) is the furthest along — a non-peptide small molecule that can be taken as a simple daily pill without food or water restrictions. Phase 3 data show it outperforms oral semaglutide [6].
Amycretin (Novo Nordisk) aims to deliver dual GLP-1/amylin activity in an oral form, though it is earlier in development.
Danuglipron (Pfizer) was the third major oral GLP-1 candidate but has been discontinued due to tolerability and safety concerns [18].

Implications for Patients

None of these investigational drugs are available for prescription. Clinical trial data, while promising, may not translate to the same results in broader populations. Regulatory review, manufacturing scale-up, and insurance coverage decisions all take time after trial completion. Patients interested in GLP-1 therapy should discuss currently available, FDA-approved options with their healthcare provider.

Sources

References

Medical Disclaimer
This content is for informational and educational purposes only. It is not intended as, and should not be interpreted as, medical advice. All drugs described on this page are investigational and not approved by the FDA unless otherwise noted. Clinical trial results are preliminary and subject to change. The information provided does not cover all possible uses, precautions, interactions, or adverse effects. It should not be used as a substitute for the advice of a qualified healthcare professional. Never disregard professional medical advice or delay seeking treatment because of something you have read here. Always speak with your doctor or pharmacist before starting, stopping, or changing any prescribed medication or treatment. GLPbase does not recommend or endorse any specific tests, physicians, products, procedures, or opinions. Use of this information is at your own risk.

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Retatrutide vs Tirzepatide — Will Triple Agonists Replace Dual? Will Oral GLP-1 Pills Change Everything? CagriSema as Wegovy's Successor — Worth Waiting For?

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GLP-1 Pipeline: What's Coming

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