Glucagon-like peptide‑1 (GLP‑1) receptor agonists have become a blockbuster class of drugs over the past few years. Originally developed for type 2 diabetes, GLP‑1 agonists are now widely used for weight management thanks to their appetite-suppressing effects and favorable metabolic profile. But as their popularity has surged, so has demand for more convenient and less invasive ways to administer them. This has spurred innovation beyond the traditional weekly or daily injections to forms like oral tablets, nasal sprays (or drops), and even lozenges. In this showdown, we compare the three main delivery routes — injections, drops, and lozenges — to understand how they stack up in terms of efficacy, safety, convenience, and real-world practicality.
The Standard: Injectable GLP‑1 Agonists
How They Work and Why They’re Popular
Injectable GLP‑1 agonists remain the gold standard. Drugs like semaglutide (sold as Ozempic or Wegovy), liraglutide, dulaglutide, and others are delivered via subcutaneous injection, typically using a pre-filled pen. The reason injectables dominate is pharmacokinetic efficiency: by injecting a peptide-based drug, it bypasses the digestive tract, avoiding degradation by stomach acid or enzymes and enabling consistent, reliable absorption. As noted in pharmacology reviews, initial GLP-1 drugs were designed as injectables because of their poor oral bioavailability.
Moreover, injectables often have long half-lives. For example, semaglutide can be dosed once weekly in its injectable forms, which improves adherence and reduces the burden on patients.
Efficacy and Safety
Clinically, injectables are proven effective for glycemic control and weight loss. According to a systematic review of GLP‑1 receptor agonists, some of the most substantial weight reductions in obesity trials came from semaglutide and tirzepatide.
However, they are not without side effects. The most common adverse reactions are gastrointestinal — nausea, diarrhea, and vomiting — which are characteristic of the GLP-1 RA class Additionally, because these drugs slow gastric emptying, there have been observations of increased gastric residue in certain patients undergoing endoscopic procedures
A further consideration is patient comfort: some people are needle-averse or reluctant to self-inject, which limits uptake even of highly effective therapies.
The Oral Alternative: Semaglutide Tablets (Daily)
Innovation Behind Oral GLP‑1
To address the barriers posed by injectable GLP-1s, pharmaceutical researchers developed an oral variant: semaglutide co-formulated with an absorption enhancer (SNAC) that helps it survive the acidic environment of the stomach and be absorbed across the gastric lining. This innovation paved the way for the first orally administered GLP-1 RA.
Clinical Outcomes: Does the Pill Work?
Yes — to a significant degree. In network meta-analyses, daily oral semaglutide (14 mg) showed robust efficacy in reducing HbA1c and body weight compared with most injectable GLP-1 RAs, especially when added to other antidiabetic therapies. In insulin-treated patients, similar results were found: oral semaglutide delivered comparable glycemic control to many injectables.
In real-world studies, the gap narrows further. A cohort study compared oral versus injectable semaglutide among patients with type 2 diabetes and found almost equal improvements in HbA1c (−1.4% oral vs. −1.1% injectable) and weight loss (−5.9 kg vs. −6.5 kg). However, persistence on treatment was observed to be longer for injectable semaglutide.
Gastrointestinal side effects remain common with oral semaglutide — nausea, vomiting, and diarrhea are frequent — but they appear to mirror those seen with injectables
Advantages and Trade-Offs
The oral pill is compelling because it avoids needles, which is a big plus for many patients. Also, taking a tablet eliminates the injection-related anxiety and handling that some find cumbersome. But there are trade-offs: oral semaglutide must be taken under strict conditions (often on an empty stomach and with water) to maximize absorption, which can be inconvenient in daily life.
Cost is another factor. A cost-of-control analysis suggested that although oral semaglutide delivers strong outcomes, its cost relative to achieving target HbA1c levels may differ depending on competing injectables
The Emerging Contenders: GLP‑1 Drops and Lozenges
Drops / Nasal GLP‑1
In more experimental territories, there is research into nasally administered GLP-1. An exploratory clinical trial in Japanese type 2 diabetes patients tested a nasal compound of native GLP-1 (7–36) and found rapid absorption: peak plasma concentrations were reached in about 8 minutes, and early insulin responses improved without significant adverse effects. Preclinical work in animals supports the plausibility: in mice, intranasal delivery of modified GLP-1 showed potent antihyperglycemic activity, matching or even surpassing subcutaneous injections over certain timeframes.
These early findings hint at a future where GLP-1 therapy could be delivered via nasal sprays or drops, combining convenience and speed. However, it’s critical to note that human data are still limited, and these formulations are not yet mainstream or widely approved for the current major GLP-1 drugs like semaglutide or tirzepatide.
Sublingual Lozenges
Lozenges (or sublingual formulations) of GLP-1 receptor agonists are largely the domain of compounding pharmacies rather than regulated, large‑scale clinical trials. There is little peer-reviewed evidence supporting their efficacy or safety. Many of these lozenges are not formally approved formulations; instead, they are compounded versions made outside of standardized pharmaceutical development pipelines.
Some anecdotal reports from users suggest that sublingual lozenges may not be very effective at therapeutic doses. For example:
“I switched to a 1.2 mg semaglutide lozenge daily … it doesn’t work … I experience no appetite suppression … the dose is not at a therapeutic level.”
Another user noted difficulty with taste and minimal effect despite prolonged use.
Because these lozenges are not well-studied, there are major unknowns: their pharmacokinetics, safety profile, real-world efficacy, and regulatory status remain ambiguous. These formulations may also bypass rigorous clinical testing and quality control, especially when compounded by smaller pharmacies. Hence, their use carries more risk and uncertainty compared to approved injectables or tablets.
Comparing the Three: Efficacy, Safety & Practicality
Efficacy
- Injectables: High and well-established efficacy. Proven in large RCTs and real-world data.
- Oral tablets: Strong, especially for glycemic control. Network meta-analyses show they rank among the top GLP-1 agents.
- Nasal/drops: Promising in small trials, but not yet robust enough for comparison.
- Lozenges: Minimal formal data; largely anecdotal mishmash from compounding pharmacies.
Safety
- Injectables: Main issue is GI side effects; some risk of delayed gastric emptying.
- Oral tablets: Similar GI side effects, plus stricter dosing constraints
- Nasal: Early trials report few adverse events, but long-term safety unknown.
- Lozenges: Safety profile unclear; compounded medicines may not go through standard toxicology or pharmacokinetic studies.
Convenience & Adherence
- Injectables: Weekly or daily shots; some dislike needles, but pen devices are user‑friendly.
- Oral tablets: Very convenient if dosing instructions (fasting, timing) are followed.
- Nasal: Could be very easy if developed further — no injections, fast onset, but requires patient education and formulation optimization.
- Lozenges: Theoretically convenient, but uncertain absorption, unpredictable effects, and unclear legitimacy make them a risky bet.
Regulatory and Real-World Considerations
Approved, regulated injectables and oral GLP-1 formulations have gone through rigorous trials and oversight. In contrast, many nasal sprays and lozenges are not FDA- or EMA-approved for standard GLP-1 drugs, especially when compounded outside pharmaceutical companies’ regulatory pipeline. This raises questions about consistency, purity, and dosing.
Patient monitoring is another concern. With well-studied formulations, clinicians know what to expect and how to manage side effects. With experimental delivery routes, there may be surprises, and long-term data are lacking.
Future Outlook: What’s Next in the GLP‑1 Arena
The GLP-1 space is evolving rapidly. Beyond current injectables and tablets, pharmaceutical companies are pushing into novel delivery platforms:
- Oral small-molecule GLP-1 agonists: For example, Lilly’s orforglipron — a daily pill candidate — has shown impressive early data in Phase 3 trials, potentially challenging both injectables and peptide-based oral therapies.
- Improved nasal or inhaled GLP-1: As preclinical and early clinical research continues, we may see more viable nasal GLP-1 agonists. The intranasal route could combine speed, convenience, and non-invasiveness.
- Innovative delivery devices: Research into ingestible devices (like “jet injection” mechanisms) aims to deliver peptides directly into the gut or other tissues while bypassing degradation.
- Regulated lozenge or sublingual products: If companies invest in clinical trials, sublingual GLP-1 formulations could become more reliable, though that would require overcoming bioavailability challenges.
Conclusion
In the GLP-1 showdown, there’s no one-size-fits-all winner. Injectable agonists remain the most proven, effective, and widely used option. Oral semaglutide offers an appealing needle-free alternative with strong clinical backing, though it comes with its own set of challenges around dosing and absorption. Emerging delivery forms — nasal sprays (“drops”) and lozenges — spark excitement for their convenience, but they’re still largely experimental. Nasal GLP-1 shows early promise, while lozenges remain largely unvalidated beyond compounding pharmacies.
For now, patients and clinicians must weigh trade-offs: efficacy, safety, convenience, cost, and regulatory legitimacy. As science and technology advance, the next generation of GLP-1 therapies may well reshape the standard of care — making effective metabolic medicine more accessible and less invasive than ever before.
