GLP-1 Agonists vs Insulin — Clinical Trial Comparison
GLP-1 Agonists
Incretin-based therapies for diabetes, obesity, and beyond
VS
Insulin
Hormone replacement for blood glucose control
GLP-1 receptor agonists have transformed the treatment landscape for type 2 diabetes and obesity, and they are now being studied across an extraordinary range of conditions — from heart failure and kidney disease to liver disease and addiction. Meanwhile, insulin remains the most essential treatment for type 1 diabetes and advanced type 2 diabetes. UK clinical trials for both approaches are abundant, and understanding how they compare can help patients navigate their options.
Key Differences at a Glance
| Feature | GLP-1 Agonists | Insulin |
|---|---|---|
| Mechanism | Mimics GLP-1 hormone — stimulates insulin, suppresses glucagon, slows gastric emptying, reduces appetite | Directly replaces or supplements natural insulin for glucose uptake into cells |
| Primary use | Type 2 diabetes, obesity, cardiovascular risk reduction | Type 1 diabetes, type 2 diabetes (when oral agents insufficient) |
| Weight effect | Significant weight loss (5–20%+ depending on agent) | Weight gain (common side effect) |
| Hypoglycaemia risk | Low (when used alone) | Significant — especially with basal-bolus regimens |
| Common drugs in trials | Semaglutide (Ozempic/Wegovy), tirzepatide (Mounjaro), retatrutide, CagriSema, orforglipron | Insulin glargine, lispro, aspart, degludec, concentrated insulins |
| Administration | Weekly injection (most), daily injection, or daily oral tablet | Daily injections (basal), multiple daily injections (bolus), insulin pumps, inhaled insulin |
Clinical Trial Availability
| Trial Aspect | GLP-1 Agonists | Insulin |
|---|---|---|
| UK trials actively recruiting | 80–150 studies | 60–100 studies |
| Most common phases | Phase 2–3 | Phase 2–3 |
| Top conditions studied | Type 2 diabetes, obesity, heart failure, NASH/MASH, CKD, sleep apnoea, PCOS | Type 1 diabetes, type 2 diabetes, gestational diabetes, hospital inpatient glucose management |
| Novel agents in trials | Retatrutide (triple agonist), CagriSema (combination), orforglipron (oral non-peptide) | Ultra-long-acting insulins, once-weekly insulins (icodec), smart insulins |
| Cardiovascular outcomes | Major focus — CVOT trials showing benefit | Required safety assessment — generally neutral |
| Beyond diabetes | Massive expansion — obesity, liver disease, kidney disease, addiction, Alzheimer's | Focused on diabetes management |
Exciting Emerging Treatments
GLP-1 Agonists Trials
- Triple agonists (retatrutide) — GLP-1 + GIP + glucagon receptor agonism
- Oral non-peptide GLP-1 — orforglipron (daily pill, no injection)
- CagriSema — combining semaglutide + cagrilintide for 25%+ weight loss
- GLP-1 for NASH/MASH — treating fatty liver disease
- GLP-1 for heart failure — cardiovascular benefits beyond diabetes
- GLP-1 for kidney disease — renal protection in diabetes and CKD
Insulin Trials
- Once-weekly insulins — icodec (insulin for once-weekly injection)
- Smart insulins — glucose-responsive insulin that self-adjusts
- Closed-loop systems — artificial pancreas (CGM + pump + algorithm)
- Ultra-rapid insulins — faster absorption for meal-time coverage
- Concentrated insulins — higher doses in smaller volumes
- Inhaled insulin advances — needle-free insulin delivery
💡 Not sure which trials you qualify for?
Use our Smart Matcher to answer a few questions about your condition and we'll find the most relevant trials for your specific situation — free, instant results.
Eligibility Differences
GLP-1 Agonists Trial Criteria
- Type 2 diabetes diagnosis (most trials) or BMI criteria (obesity trials)
- HbA1c within trial-specific range (typically 6.5–10%)
- Some trials require prior metformin or other diabetes medication failure
- Obesity trials: BMI ≥ 30 (or ≥ 27 with comorbidity)
- No personal/family history of medullary thyroid carcinoma (for GLP-1 trials)
- No active pancreatitis
Insulin Trial Criteria
- Type 1 or type 2 diabetes requiring insulin therapy
- HbA1c above target on current regimen
- Willingness to perform regular blood glucose monitoring
- No severe hypoglycaemia unawareness (for some trials)
- Ability to manage injection or pump therapy
- Appropriate prior treatment history
GLP-1 Agonist Trials
Find actively recruiting GLP-1 agonist clinical trials across the UK
GLP-1 Agonist TrialsFrequently Asked Questions
Are GLP-1 agonists replacing insulin for type 2 diabetes?
Not replacing, but they are being used earlier and more often. For many patients with type 2 diabetes, GLP-1 agonists are now recommended before insulin because of their weight loss benefits and lower hypoglycaemia risk. However, insulin remains essential for type 1 diabetes and for type 2 patients who have lost significant beta cell function.
Can I take a GLP-1 agonist and insulin together?
Yes — this is increasingly common and many trials study the combination. Fixed-ratio products like insulin degludec/liraglutide (Xultophy) combine both. Your endocrinologist can advise on whether combination therapy is appropriate for your situation.
What conditions beyond diabetes and obesity are GLP-1 agonists being tested for?
The list is growing rapidly: heart failure (preserved and reduced ejection fraction), NASH/MASH (fatty liver disease), chronic kidney disease, sleep apnoea, PCOS, Alzheimer's disease, addictive behaviours, and even certain cancers. The metabolic and anti-inflammatory effects of GLP-1 agonists appear to have wide-ranging benefits.