Peptide Delivery Innovations: Patches, Implants, Orals

Most peptide drugs arrive in the body the same way they did 30 years ago: through a needle. Subcutaneous injections work, but they impose a burden that limits who will use peptide therapies and how consistently they'll take them. Needles hurt. They require cold-chain storage. They generate medical waste. And for millions of potential patients, the psychological barrier of self-injection is the reason they never start treatment at all.

That's changing. In 2025, a South Korean company demonstrated a semaglutide microneedle patch with over 80% bioavailability in humans — comparable to injection. The FDA approved the first oral GLP-1 for weight management. Eli Lilly's orforglipron showed that a pill could maintain weight loss achieved with injectables. And implantable devices, nasal sprays, and programmable release systems are moving through development pipelines.

This article covers the technologies that are making needles optional — and what that means for patient access and adherence.

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Table of Contents

• Why Delivery Innovation Matters for Peptides
• Microneedle Patches: The Closest Alternative to Injection
• Oral Peptide Delivery: Overcoming the Gut
• Subcutaneous Implants and Depot Systems
• Nasal Delivery: Fast Absorption, Specific Applications
• Patient Preference Data: What People Actually Want
• Comparing Delivery Routes: A Practical Guide
• What's Coming Next
• FAQ
• The Bottom Line
• References

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Why Delivery Innovation Matters for Peptides

Peptides face a fundamental delivery problem that small-molecule drugs don't. Most peptides are chains of 5-50 amino acids with molecular weights above 700 daltons. They're hydrophilic, meaning they can't easily cross cell membranes or the intestinal lining. They're fragile — stomach acid and digestive enzymes destroy them within minutes. And they're too large to pass through intact skin.

These properties explain why injection has been the default. Subcutaneous delivery bypasses every barrier: no stomach acid, no digestive enzymes, no skin to cross. The peptide goes directly into tissue, absorbs into the bloodstream, and reaches its target.

The problem is that injection-based therapies have adherence rates far below what clinical trials assume. For chronic conditions requiring lifelong treatment — like obesity managed with semaglutide — the gap between clinical trial adherence and real-world adherence translates directly into reduced effectiveness.

The delivery innovation landscape breaks into four main categories, each with different maturity levels and trade-offs.

Microneedle Patches: The Closest Alternative to Injection

Microneedle (MN) technology is the most advanced alternative to traditional injection for peptide delivery. These patches contain arrays of microscopic projections — typically 100-1,500 micrometers long — that penetrate the outermost skin layer (stratum corneum) without reaching the nerve-rich deeper dermis. The result: drug delivery to the same subcutaneous space that a syringe reaches, but with minimal or no pain.

How Microneedle Patches Work

MN patches come in several designs, each with different drug loading and release characteristics:

Dissolving microneedles (DMNs): The needle tips are made from biodegradable polymers (like hyaluronic acid, chitosan, or polyvinyl pyrrolidone) that encapsulate the drug. After insertion into the skin, the tips dissolve upon contact with interstitial fluid, releasing their payload. No sharps waste remains — the backing patch is discarded as regular waste.

Coated microneedles: Solid needles coated with a drug formulation. The coating dissolves after insertion, depositing the drug. These work well for vaccines and single-dose applications but have limited drug-loading capacity.

Hollow microneedles: Miniaturized hypodermic needles that deliver liquid formulations through the skin. They offer the highest drug-loading capacity but are more complex to manufacture.

Hydrogel-forming microneedles: Swellable polymer tips that absorb interstitial fluid and release drug in a controlled manner. These can achieve sustained release over hours to days.

Materials used in fabrication include silicon, polymers, sugars, ceramics, metals, and glass — each offering different mechanical, biocompatibility, and drug-stability properties.

The Semaglutide Patch Breakthrough

The most significant microneedle development for peptide therapeutics came from Daewoong Therapeutics in South Korea. Using their proprietary CLOPAM (Closed Aseptic Manufacturing) platform, they created a dissolving microneedle patch that delivered semaglutide with over 80% relative bioavailability compared to subcutaneous injection — the highest reported for any microneedle peptide delivery system.

The pilot human pharmacokinetic study enrolled 70 healthy adults who received either a single-dose semaglutide microneedle patch or subcutaneous injection. Key findings:

• 80%+ bioavailability — previous microneedle semaglutide attempts had achieved only about 30%
• Approximately 160 times higher absorption than oral semaglutide tablets
• Therapeutic plasma levels maintained for one week, supporting potential once-weekly dosing
• Room-temperature stability — unlike injectable semaglutide requiring cold-chain storage

The CLOPAM platform uses pressurized drying and hermetic packaging to improve drug uniformity and stability within the microneedle matrix. Daewoong is pursuing global commercialization through technology licensing and co-development partnerships.

Glucose-Responsive Insulin Patches

Beyond GLP-1 agonists, microneedle technology is advancing rapidly for insulin delivery. Several research groups have developed "smart" patches that release insulin in response to blood glucose levels:

A 2024 study in ACS Nano described a triple-layer microneedle with a glucose-responsive shell, an insulin-loaded compartment, and a color-changing propulsion core. The patch selectively releases insulin when blood glucose rises, mimicking the pancreas's natural response.

Researchers at MIT published a wearable microneedle patch in Microsystems & Nanoengineering with PEG functionalization that extended insulin stability from days to weeks, demonstrating closed-loop blood glucose control in diabetic rats.

The One-Month Patch

Perhaps the most ambitious microneedle concept is a programmable scheduled-release system that delivers semaglutide for an entire month from a single 2 cm x 2 cm patch. The system uses four programmable core-shell microneedle arrays that release semaglutide every 7 days, sustaining drug efficacy for an unprecedented one-month period — simulating the effect of four weekly injections.

This concept is still in preclinical development, but it represents the potential endpoint of microneedle technology: apply a patch once a month and forget about it.

Oral Peptide Delivery: Overcoming the Gut

Oral delivery is the holy grail of peptide pharmaceutics. Patients overwhelmingly prefer pills to injections. But getting a peptide through the gastrointestinal tract intact is one of the hardest problems in drug delivery.

The Barriers

The GI tract is specifically designed to destroy proteins and peptides. The challenges include:

• Acid degradation: Stomach pH of 1-3 rapidly hydrolyzes peptide bonds
• Enzymatic degradation: Pepsin, trypsin, chymotrypsin, and other proteases systematically cleave peptides
• Poor membrane permeability: Peptides above ~700 daltons can't easily cross the intestinal epithelium
• First-pass metabolism: Whatever survives the gut faces hepatic metabolism before reaching systemic circulation
• Mucus barrier: A thick mucus layer coating the intestinal wall physically blocks large molecules

The result: oral bioavailability for most unformulated peptides is below 1%. Oral semaglutide (Rybelsus) achieves only about 0.4-1% bioavailability even with its absorption enhancer — meaning more than 99% of each dose is destroyed or never absorbed.

Oral Semaglutide: The Current Standard

Oral semaglutide was the first oral GLP-1 receptor agonist approved by the FDA (as Rybelsus for type 2 diabetes). It uses a chemical trick: co-formulation with sodium N-(8-[2-hydroxylbenzoyl] amino) caprylate (SNAC), an absorption enhancer that increases local pH in the stomach, improves drug solubility, and protects against proteolytic degradation.

The technology works, but with significant limitations. Patients must take it on an empty stomach, at least 30 minutes before food or other medications, with no more than 4 ounces of plain water. These dosing restrictions — which improve but don't eliminate the absorption challenge — reduce real-world convenience.

In late 2025, the FDA approved a higher-dose oral semaglutide (25 mg) as the first oral GLP-1 for weight management, with pricing at $149/month and availability beginning January 2026. The OASIS 4 trial supporting this approval showed 13.6% body weight reduction versus 2.2% for placebo at 64 weeks.

Orforglipron: The Small-Molecule Approach

Orforglipron represents a fundamentally different strategy. Instead of trying to get a peptide through the gut intact, Eli Lilly designed a small-molecule compound that activates the GLP-1 receptor without being a peptide at all. This means inherently better oral bioavailability — no SNAC needed, no empty-stomach requirement, no 99% destruction rate.

Phase 3 results from the ATTAIN-1 trial (NEJM, 2025) enrolled 3,127 non-diabetic patients with obesity. At 72 weeks:

• Low dose (6 mg): 7.8% weight loss
• Medium dose (12 mg): 9.3% weight loss
• High dose (36 mg): 12.4% weight loss
• Placebo: 2.1% weight loss

These results are somewhat less than injectable semaglutide or tirzepatide, but the metabolic benefits — reductions in waist circumference, blood pressure, cholesterol, and triglycerides — were substantial.

A first-of-its-kind Phase 3 switching study showed that patients who switched from injectable semaglutide to oral orforglipron maintained their previously achieved weight loss (-0.1 kg change vs. +9.4 kg for placebo over 24 weeks). This suggests oral GLP-1 therapy can sustain the benefits of injection-based treatment.

Device-Based Oral Delivery

Several device-based approaches aim to deliver peptides directly through the GI wall, bypassing the luminal degradation problem entirely:

RaniPill (Rani Therapeutics): A robotic pill containing sucrose-based microneedles activated by an osmotic, self-inflating balloon within an HPMC capsule. As the capsule dissolves, the balloon inflates and pushes drug-loaded microneedles into the intestinal wall. The company has completed human studies for multiple peptide drugs.

SOMA (MIT/Novo Nordisk): A self-orienting millimeter-scale applicator designed to deliver peptides through the stomach wall. The device orients itself to the gastric epithelium using a weighted bottom (inspired by leopard tortoise shell geometry) and actuates spring-loaded peptide-filled milliposts. This was the first study to demonstrate systemic peptide delivery via physical disruption of the stomach wall.

LUMI (MIT): A luminal unfolding microneedle injector that deploys in the small intestine. Upon encountering pH above 5.5, the capsule ruptures and folding arms with microneedle arrays penetrate the intestinal mucosa to release macromolecule drugs.

These devices are still in clinical development, but they represent a third pathway between chemical formulation (SNAC) and small-molecule design (orforglipron): mechanical delivery that physically gets peptides past the gut barrier.

Subcutaneous Implants and Depot Systems

Implantable drug delivery systems trade the convenience of a pill for the advantage of set-and-forget dosing over weeks or months. For peptides that require chronic administration — GLP-1 agonists, growth hormone-releasing peptides, gonadotropin-releasing hormone analogs — implants could eliminate daily or weekly dosing entirely.

Current Implant Technologies

Several implant approaches are in development or clinical use for peptide delivery:

Biodegradable polymer implants: Peptides encapsulated in PLGA (poly[lactic-co-glycolic acid]) or similar biodegradable polymers that slowly release drug as the matrix degrades. Release duration can be tuned from weeks to months based on polymer composition. The 2025 development of a double-layered PLGA microparticles-dissolving microneedle system for sustained transdermal peptide delivery shows how implant and patch technologies are converging.

Adhesive proteinic microneedle patches: Yang et al. developed an acrylated adhesive proteinic microneedle patch for local drug delivery and stable device implantation, published in the Journal of Controlled Release (2024). These function as miniature implants — microneedles embed in tissue and release drug over extended periods.

Osmotic implants: Subcutaneous devices that use osmotic pressure to drive controlled drug release. Existing examples include Viadur (leuprolide for prostate cancer, now discontinued) and experimental devices for GLP-1 delivery.

Advantages and Limitations

Implants offer near-perfect adherence — once placed, the patient can't forget a dose. They provide steady-state drug levels without the peaks and troughs of intermittent dosing. And they eliminate injection-related waste.

The trade-offs include the need for a placement procedure (and removal for non-biodegradable devices), limited drug-loading capacity, manufacturing complexity, and the challenge of adjusting doses once an implant is placed.

Nasal Delivery: Fast Absorption, Specific Applications

Nasal delivery offers rapid systemic absorption through the highly vascularized nasal mucosa, bypassing first-pass hepatic metabolism. The nasal route is particularly suited for peptides that need fast onset — like insulin for glucose emergencies or peptides targeting the central nervous system.

Nasal Peptide Products

Several peptide products already use nasal delivery:

• Desmopressin nasal spray for diabetes insipidus and bedwetting
• Nafarelin (GnRH analog) for endometriosis
• Calcitonin nasal spray for osteoporosis (withdrawn in some markets)

For research peptides, nasal delivery has been explored for compounds like selank and semax, which target the central nervous system and benefit from the nose-to-brain pathway that partially bypasses the blood-brain barrier.

Limitations

Nasal delivery has capacity constraints — the nasal cavity can hold only about 150-200 microliters per nostril, limiting the dose that can be delivered in a single application. Nasal mucociliary clearance reduces contact time with the absorptive mucosa. And chronic nasal delivery can cause local irritation, potentially affecting patient acceptance for long-term therapy.

These limitations make nasal delivery most suitable for peptides with low effective doses and fast-onset requirements, rather than high-dose, chronic-treatment peptides like GLP-1 agonists.

Patient Preference Data: What People Actually Want

The practical value of any delivery innovation depends on whether patients actually prefer it. Research consistently shows that they do — overwhelmingly.

Injection Avoidance

Multiple studies document that fear of needles (trypanophobia) affects 20-30% of adults and is a significant barrier to treatment initiation and adherence. For peptide therapies requiring self-injection — like GLP-1 agonists — this translates directly into patients who never start treatment or discontinue prematurely.

Microneedle Preference Data

Studies consistently show that microneedle delivery is perceived as less painful than conventional subcutaneous injection. In comparative studies, subjects found microneedles less painful and preferred them overall compared to subcutaneous catheters. Beyond reduced pain, microneedle delivery increased insulin pharmacokinetics almost two-fold — suggesting that the delivery route itself may improve drug performance.

Patient preference for MN patches extends beyond pain reduction. Room-temperature stability eliminates the need for refrigeration. Self-application without medical training removes a barrier to independent use. And the absence of sharps waste simplifies disposal and reduces biohazard concerns.

Oral Preference

The preference for oral medications over injections is so strong it barely needs citing, but the magnitude matters. Surveys of patients with type 2 diabetes consistently show 75-90% preference for oral over injectable medications when efficacy is comparable. The approval of oral semaglutide for weight management and the development of orforglipron directly address this preference.

Comparing Delivery Routes: A Practical Guide

Feature	SC Injection	Microneedle Patch	Oral (peptide)	Oral (small molecule)	Nasal	Implant
Bioavailability	~100%	30-80%+	0.4-1%	Higher (varies)	10-50%	~100%
Pain	Moderate	Minimal/none	None	None	None	Placement only
Dosing frequency	Weekly-daily	Weekly-monthly	Daily	Daily	Daily-multiple	Weeks-months
Storage	Cold chain	Room temp	Room temp	Room temp	Room temp	N/A (in situ)
Self-administration	Yes (training)	Yes (easy)	Yes (easy)	Yes (easy)	Yes (easy)	No (placement)
Adherence barrier	Needle fear	Low	Dosing rules	Low	Nasal irritation	Very low
Maturity	Established	Late clinical	Approved	Phase 3	Established	Early clinical

What's Coming Next

The delivery innovation pipeline is moving faster than at any point in peptide therapeutics history.

Microneedle commercialization: Daewoong's semaglutide patch is pursuing regulatory pathways across global markets. If approved, it would be the first microneedle patch for a major peptide therapeutic, potentially reshaping the $60 billion obesity drug market.

Oral GLP-1 expansion: With oral semaglutide approved for weight management and orforglipron in late-stage trials, oral delivery will become a standard option for GLP-1 therapy within 1-2 years. Other oral GLP-1 candidates are in earlier development stages.

Smart delivery systems: Glucose-responsive insulin patches, programmable-release microneedle arrays, and closed-loop wearable systems are moving from proof-of-concept to clinical testing. These systems could adapt drug delivery to real-time physiological needs.

Combination platforms: Researchers are exploring delivery systems that combine multiple peptides in a single device — for example, co-delivering a GLP-1 agonist and an amylin analog from a single patch or implant, simplifying multi-drug regimens.

AI-optimized formulations: Machine learning is being applied to optimize formulation parameters — polymer composition, microneedle geometry, absorption enhancer selection — accelerating the development of new delivery systems.

FAQ

Is there an Ozempic patch available?

Not yet. No semaglutide microneedle patch has received FDA approval. Daewoong Therapeutics has completed a pilot human study showing over 80% bioavailability with their semaglutide patch, but it's still in clinical development. Products marketed online as "Ozempic patches" or "semaglutide patches" are not legitimate FDA-approved medications.

How does the bioavailability of oral semaglutide compare to injection?

Oral semaglutide (using the SNAC absorption enhancer) achieves only about 0.4-1% bioavailability compared to injection. This means doses must be much higher to achieve comparable drug levels — the oral weight management dose is 25 mg versus 2.4 mg for injection. Orforglipron, a small-molecule GLP-1 agonist, has inherently higher oral bioavailability because it's not a peptide.

Are microneedle patches painless?

Clinical studies consistently report minimal to no pain with microneedle patches, and patients prefer them over conventional injections. The needles penetrate only the outermost skin layer (stratum corneum) without reaching pain-sensing nerve endings in the deeper dermis. Most participants in studies describe the sensation as less painful than a standard subcutaneous injection.

Could implants replace daily or weekly peptide injections?

In principle, yes. Biodegradable polymer implants can provide sustained peptide release over weeks to months, eliminating dosing adherence as a concern. The technology exists for some peptide hormones (like GnRH analogs). For GLP-1 agonists, implant-based delivery is in earlier development stages, with the main challenges being drug loading capacity and the need for a placement procedure.

What happened to Pfizer's oral GLP-1 drug?

Pfizer discontinued clinical development of danuglipron, its once-daily oral GLP-1 receptor agonist candidate for obesity. In a dose optimization study, an asymptomatic patient experienced potential drug-induced liver injury, which resolved after discontinuation. This highlights the development risk in the oral GLP-1 space — not every candidate will make it to market.

The Bottom Line

The era of injection-only peptide delivery is ending. Microneedle patches have achieved 80%+ bioavailability for semaglutide in human trials. Oral semaglutide is FDA-approved for weight management. Orforglipron proves that small-molecule GLP-1 agonists can maintain injectable-level weight loss. And programmable release systems, glucose-responsive patches, and implant-based delivery are advancing through clinical development.

Each technology addresses different patient needs. Microneedle patches offer injection-equivalent efficacy without needles or cold storage. Oral formulations provide the convenience patients overwhelmingly prefer. Implants promise weeks-to-months of hands-free delivery. Nasal sprays enable rapid onset for specific applications.

The competitive dynamics are straightforward: whichever delivery innovations reach market first will capture enormous patient populations currently limited by injection aversion. With the obesity therapeutics market projected to reach $60.5 billion by 2030, the stakes for delivery technology are as high as the stakes for the drugs themselves.

For patients, the message is simple. The needles are becoming optional. The question is no longer whether non-injectable peptide delivery will be available — it's which form will work best for you.

References

1. Daewoong Therapeutics. "Microneedle Patch Achieves Best-in-Class Bioavailability, Proving the Strength of Its Drug-Delivery Platform." Press Release. 2025. BioSpace

2. European Pharmaceutical Review. "Daewoong's microneedle patch marks semaglutide first in obesity." 2025. EPR

3. Fonseca VA, et al. "Oral Semaglutide." Clinical Diabetes. 2020. PMC

4. Jepsen CH, et al. "Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment." New England Journal of Medicine. 2025. NEJM

5. FDA. "FDA Approves Oral Semaglutide as First GLP-1 Pill for Weight Loss." 2025. AJMC

6. Zhang G, et al. "Glucose-Responsive Microneedle Patch with High Insulin Loading." ACS Nano. 2024. ACS

7. Zhu Y, et al. "A wearable, rapidly manufacturable, stability-enhancing microneedle patch for closed-loop diabetes management." Microsystems & Nanoengineering. 2024. Nature

8. Li W, et al. "Single-Administration Self-Boosting Microneedle Patch for The Treatment of Obesity." ACS Nano. 2024. PubMed

9. Abramson A, et al. "Recent Progress in the Oral Delivery of Therapeutic Peptides and Proteins." Pharmaceutics. 2024. PMC

10. Barriers and Strategies for Oral Peptide and Protein Therapeutics Delivery: Update on Clinical Advances. Pharmaceutics. 2025. PMC

11. Springer. "Advancements in transdermal drug delivery using microneedles: technological and material perspective." Discover Pharmaceutical Sciences. 2025. Springer

12. Liu C, et al. "Transdermal Semaglutide Administration in Mice: Reduces Body Weight by Suppressing Appetite and Enhancing Metabolic Rate." Obesity. 2025. PMC