Clinical Reference · February 2026

GLP-1 Receptor Agonist Compendium

Comprehensive quick-reference for all approved incretin-based therapies

11
Approved Products
6
Distinct Molecules
3
CV Benefit Proven
2
Dual Agonists
⚡

Short-Acting Agents

Predominantly postprandial glucose control
Byetta®
exenatide (immediate-release)
Twice Daily T2DM S/C
ManufacturerAstraZeneca
Half-Life2.4 hours
First Approved2005 (FDA)

Dosing

Starting dose5 µg BD × 1 month
Target dose10 µg BD
Administration60 min before meals (breakfast & dinner)
Pen devicePre-filled pen (5 µg, 10 µg)
Renal dosingCaution eGFR 30–50; avoid <30

Pharmacology

ClassExendin-4 based
Homology to GLP-153%
Half-life2.4 hours
Tmax~2 hours
EliminationRenal (glomerular filtration + proteolysis)
Primary actionPostprandial glucose ↓ (gastric emptying delay)

Efficacy

HbA1c reduction−0.8 to −1.0%
Weight change−1.5 to −3.0 kg
FPG reductionModest
PPG reductionMarked (primary effect)
CV outcomeNon-inferior (EXSCEL — ER formulation)

Side Effects & Cautions

  • Nausea (44%), vomiting (13%), diarrhoea (13%) — usually transient
  • Injection site reactions (5.1%)
  • Hypoglycaemia risk when combined with SU / insulin
  • Rare: acute pancreatitis — discontinue if suspected
  • Contraindicated: severe renal impairment (eGFR <30), personal/family MTC, MEN2
  • Not studied in gastroparesis — avoid in severe GI motility disorders
Lyxumia® / Adlyxin®
lixisenatide
Once Daily T2DM S/C
ManufacturerSanofi
Half-Life~3 hours
First Approved2013 (EMA) / 2016 (FDA)

Dosing

Starting dose10 µg OD × 14 days
Target dose20 µg OD
Administration60 min before first meal of the day
Pen devicePre-filled green (10 µg) / purple (20 µg) pen
Renal dosingNo adjustment eGFR 30–80; caution 15–30; avoid <15

Pharmacology

ClassExendin-4 based (modified)
Homology to GLP-150%
Half-life~3 hours
Primary actionPPG reduction via gastric emptying delay
Antibody formationHigher rate (~70%) — rarely clinically relevant

Efficacy

HbA1c reduction−0.7 to −0.9%
Weight change−1.0 to −2.5 kg
PPG reductionMarked (strongest PPG effect in class)
CV outcomeNon-inferior (ELIXA trial)
Key trialGetGoal programme

Side Effects & Cautions

  • Nausea (26%), vomiting (10%), diarrhoea (8%)
  • Headache (9%)
  • Hypoglycaemia when combined with SU
  • May delay absorption of co-administered oral meds — take 1 hr before lixisenatide
  • Good option as add-on to basal insulin (forms basis of Suliqua combination)
🕐

Long-Acting Agents — Daily Injectable

FPG + PPG coverage
Victoza®
liraglutide 1.2 mg / 1.8 mg
Once Daily T2DM CV Benefit ✓ S/C
ManufacturerNovo Nordisk
Half-Life13 hours
First Approved2009 (EMA) / 2010 (FDA)

Dosing

Starting dose0.6 mg OD × 1 week
Escalation→ 1.2 mg OD (min. effective dose)
Max dose1.8 mg OD
AdministrationAny time of day, with or without food
Pen deviceMulti-dose pre-filled pen (6 mg/mL)
Renal dosingCaution in severe renal impairment; limited experience

Pharmacology

ClassHuman GLP-1 analogue (acylated)
Homology to GLP-197%
Half-life13 hours
Mechanism of prolongationAlbumin binding via C16 fatty acid chain
EliminationEndogenous peptide metabolism (not organ-specific)

Efficacy & Key Trials

HbA1c reduction−1.0 to −1.5%
Weight change−2.0 to −3.5 kg
📋 LEAD programme ❤️ LEADER — 13% ↓ 3-point MACE
CV outcomeSuperior — MACE reduction (HR 0.87)
Renal benefit↓ new-onset persistent macroalbuminuria (LEADER)

Side Effects & Cautions

  • Nausea (28%), diarrhoea (17%), vomiting (11%)
  • GI side effects usually peak weeks 4–8 then improve
  • ↑ Heart rate (~3 bpm) — monitor if pre-existing tachyarrhythmia
  • Acute pancreatitis (rare) — discontinue if suspected
  • Cholelithiasis (particularly with rapid weight loss)
  • Black box (FDA): Thyroid C-cell tumours in rodents — contraindicated in personal/family MTC, MEN2
Saxenda®
liraglutide 3.0 mg (high-dose)
Once Daily Obesity S/C
ManufacturerNovo Nordisk
Max Dose3.0 mg OD
First Approved2014 (FDA) / 2015 (EMA)

Dosing

Week 10.6 mg OD
Week 21.2 mg OD
Week 31.8 mg OD
Week 42.4 mg OD
Week 5+3.0 mg OD (maintenance)
IndicationBMI ≥30, or ≥27 + comorbidity
Discontinuation ruleStop if <5% weight loss at 12 weeks on 3.0 mg

Efficacy & Key Trials

Mean weight loss−5.4 to −8.0% (SCALE trials)
≥5% responders~63%
≥10% responders~33%
📋 SCALE Obesity & Prediabetes 📋 SCALE Diabetes 📋 SCALE Maintenance
T2D prevention↓ risk of T2D onset by 79% at 3 years (SCALE)

Side Effects & Cautions

  • Higher GI side effects at 3.0 mg dose (nausea ~40%)
  • ↑ Heart rate — mean 2–3 bpm
  • Acute gallbladder events reported more frequently
  • Suicidal ideation monitoring recommended (post-marketing)
  • Weight regain common after discontinuation
  • Same contraindications as Victoza (MTC, MEN2)

UK Prescribing (NICE)

  • NICE TA664 (2020): Recommended as option for weight management
  • BMI ≥35 (or ≥32.5 in certain ethnic groups) + comorbidity
  • Specialist weight management service setting
  • Maximum treatment duration 2 years; stop if <5% loss at 12 weeks
📅

Long-Acting Agents — Weekly Injectable

Sustained FPG + PPG coverage
Bydureon® BCise
exenatide extended-release
Once Weekly T2DM S/C
ManufacturerAstraZeneca
Dose2 mg once weekly
First Approved2012 (FDA) / 2011 (EMA)

Dosing

Dose2 mg once weekly (no titration)
AdministrationAny time of day, with or without food
DeviceBCise single-dose autoinjector
Needle gauge23G (microsphere suspension)
Steady state6–7 weeks
RenalCaution eGFR 30–50; avoid <30

Efficacy

HbA1c reduction−1.3 to −1.6%
Weight change−2.0 to −3.0 kg
📋 DURATION programme ❤️ EXSCEL — CV neutral (HR 0.91, NS)
CV outcomeNon-inferior (EXSCEL)

Side Effects & Cautions

  • Injection site nodules (10–16%) — unique to microsphere formulation
  • Nausea lower than BD exenatide (~10%)
  • Anti-exenatide antibodies in ~45% (high titre in 12%)
  • Same class warnings: pancreatitis, MTC (rodent signal)
  • Note: Being withdrawn/discontinued in some markets — check local availability
Trulicity®
dulaglutide
Once Weekly T2DM CV Benefit ✓ S/C
ManufacturerEli Lilly
Half-Life~5 days
First Approved2014 (FDA & EMA)

Dosing

Starting dose0.75 mg once weekly
Dose range0.75 / 1.5 / 3.0 / 4.5 mg weekly
EscalationIncrease every 4 weeks as tolerated
DeviceSingle-use pre-filled pen (hidden needle)
Injection sitesAbdomen, thigh, upper arm
RenalNo dose adjustment; caution initiating/escalating in renal impairment

Pharmacology

StructureGLP-1 analogue fused to modified IgG4-Fc
Homology to GLP-190%
Half-life~5 days (120 hours)
Mechanism of prolongationLarge molecule size (Fc fusion) → ↓ renal clearance
Bioavailability47–65% (dose-dependent)

Efficacy & Key Trials

HbA1c reduction−1.1 to −1.6% (dose-dependent)
Weight change−1.5 to −4.6 kg
📋 AWARD programme (1–11) ❤️ REWIND — 12% ↓ MACE
CV outcomeSuperior — MACE reduction (HR 0.88)
Special noteREWIND enrolled 31% without established CVD — broadest population

Side Effects & Cautions

  • Nausea (21%), diarrhoea (13%), vomiting (12%)
  • ↑ Heart rate (2–4 bpm)
  • Good injection compliance (hidden needle, once weekly)
  • Standard class warnings: pancreatitis, gallbladder events, MTC
  • Lowest immunogenicity among GLP-1 RAs (~1.6% antibodies)
Ozempic®
semaglutide (subcutaneous)
Once Weekly T2DM CV Benefit ✓ S/C
ManufacturerNovo Nordisk
Half-Life~7 days
First Approved2017 (FDA) / 2018 (EMA)

Dosing

Starting dose0.25 mg weekly × 4 weeks
Step 20.5 mg weekly × ≥4 weeks
Max dose1.0 mg weekly (2.0 mg in some markets)
DeviceMulti-dose FlexTouch® pen (0.25/0.5 mg or 1.0 mg)
NeedleNovoFine® Plus 32G tip
RenalNo dose adjustment required; caution in severe

Pharmacology

StructureHuman GLP-1 analogue (94% homology)
ModificationsAib8 substitution + C18 fatty diacid via linker
Half-life~165 hours (7 days)
Mechanism of prolongationStrong albumin binding + DPP-4 resistance
Steady state4–5 weeks

Efficacy & Key Trials

HbA1c reduction−1.5 to −1.8% (best-in-class for T2D)
Weight change−4.0 to −6.5 kg
📋 SUSTAIN 1–10 ❤️ SUSTAIN 6 — 26% ↓ MACE ❤️ SELECT — 20% ↓ MACE (obesity ± T2D)
CV outcomeSuperior — MACE reduction (HR 0.74 SUSTAIN-6)
SELECT trialFirst GLP-1 RA with MACE benefit in obesity without T2D

Side Effects & Cautions

  • Nausea (20%), vomiting (9%), diarrhoea (15%)
  • Cholelithiasis / cholecystitis (especially higher doses)
  • Diabetic retinopathy complications in SUSTAIN-6 (early worsening with rapid HbA1c ↓)
  • Standard class warnings: pancreatitis, MTC, ↑ HR
  • Consider ophthalmology review if pre-existing retinopathy before initiation
Wegovy®
semaglutide 2.4 mg (high-dose)
Once Weekly Obesity CV Benefit ✓ S/C
ManufacturerNovo Nordisk
Max Dose2.4 mg weekly
First Approved2021 (FDA) / 2022 (EMA)

Dosing Escalation

Month 10.25 mg weekly
Month 20.5 mg weekly
Month 31.0 mg weekly
Month 41.7 mg weekly
Month 5+2.4 mg weekly (maintenance)
IndicationBMI ≥30, or ≥27 + comorbidity
AdolescentsApproved ≥12 yrs (BMI ≥95th centile)

Efficacy & Key Trials

Mean weight loss−14.9% at 68 wks (STEP 1)
≥5% responders~86%
≥10% responders~70%
≥20% responders~32%
📋 STEP 1–5 ❤️ SELECT — 20% ↓ MACE (HR 0.80) 📋 STEP HFpEF — improved symptoms & exercise
CV outcomeSuperior — SELECT trial (independent of diabetes)
HFpEFImproved Kansas City score, 6MWD, and CRP

Side Effects & Cautions

  • GI side effects common (nausea 44%, diarrhoea 30%, vomiting 25%)
  • Most GI events are mild-moderate and transient
  • Gallbladder events (cholelithiasis, cholecystitis)
  • Rapid weight loss: monitor for nutritional deficiency, sarcopenia
  • Weight regain: ~67% of weight regained at 1 year post-discontinuation (STEP 1 extension)
  • Consider resistance/protein optimisation alongside pharmacotherapy

UK Prescribing (NICE)

  • NICE TA875 (2023): Recommended for weight management
  • BMI ≥35 (≥32.5 adjusted) + ≥1 weight-related comorbidity
  • Specialist weight management setting (Tier 3/4)
  • Maximum treatment 2 years; stop if <5% loss at 6 months on maintenance
  • Now also approved post-SELECT for CV risk reduction (FDA 2024)
💊

Oral GLP-1 Receptor Agonist

First-in-class oral formulation
Rybelsus®
oral semaglutide
Once Daily T2DM Oral
ManufacturerNovo Nordisk
FormulationSNAC co-formulation
First Approved2019 (FDA) / 2020 (EMA)

Dosing

Starting dose3 mg OD × 30 days
Step 27 mg OD × ≥30 days
Max dose14 mg OD
Critical instructionsTake fasting with ≤120 mL water; wait ≥30 min before food/drink/other meds
Note3 mg is a titration dose — not clinically effective
Bioavailability~1% (SNAC enhancer required)

Pharmacology

Active moleculeSame semaglutide as Ozempic
Absorption enhancerSNAC (salcaprozate sodium) — ↑ gastric absorption
Half-life~1 week (once absorbed, same PK)
Steady state4–5 weeks
Food effectMajor — absorption ↓↓ with food (must take fasting)

Efficacy & Key Trials

HbA1c reduction (14 mg)−1.0 to −1.4%
Weight change−2.5 to −4.5 kg
📋 PIONEER 1–10 📋 PIONEER 6 (CV safety — non-inferior) 📋 PIONEER PLUS — 25 mg & 50 mg under investigation
PIONEER 6Non-inferior for MACE (pre-approval safety trial)
Higher dosesOral sema 25/50 mg showing ↑ efficacy in trials

Side Effects & Practical Considerations

  • Similar GI profile to SC semaglutide (nausea ~20%, diarrhoea, constipation)
  • Strict fasting protocol — impacts compliance/lifestyle
  • Drug interactions: levothyroxine, PPIs — separate timing
  • Not recommended in severe GI disease (may affect absorption)
  • Efficacy slightly lower than SC semaglutide 1 mg at currently approved doses
  • Useful for patients preferring oral route / needle aversion
🔬

Dual Incretin Agonists

GIP/GLP-1 receptor agonism
Mounjaro®
tirzepatide (dual GIP/GLP-1 RA)
Once Weekly T2DM S/C Dual Agonist
ManufacturerEli Lilly
Half-Life~5 days
First Approved2022 (FDA) / 2022 (EMA)

Dosing

Starting dose2.5 mg weekly × 4 weeks
Step 25 mg weekly × ≥4 weeks
Dose range5 / 7.5 / 10 / 12.5 / 15 mg weekly
DeviceKwikPen® single-dose pre-filled
RenalNo dose adjustment required
HepaticNo dose adjustment required

Pharmacology

ClassDual GIP + GLP-1 receptor agonist ("twincretin")
Structure39-AA peptide based on GIP sequence
GIP:GLP-1 affinityEqual GIP; 5× lower GLP-1 (vs native)
Half-life~5 days (116 hours)
Mechanism of prolongationC20 fatty diacid → albumin binding
Key differenceGIP agonism → additional adipose tissue effects, ↑ insulin sensitivity

Efficacy & Key Trials

HbA1c reduction−1.9 to −2.6% (unprecedented in class)
HbA1c <5.7%Up to 46% achieved normoglycaemia (SURPASS-4)
Weight change (T2D)−5.4 to −12.9 kg (SURPASS)
📋 SURPASS 1–5 (T2DM) 📋 SURPASS vs semaglutide 1 mg → superior HbA1c + weight 📋 SURPASS-CVOT (ongoing)
Head-to-head vs OzempicAll doses superior for HbA1c & weight (SURPASS-2)
CVOTSURPASS-CVOT ongoing — results expected ~2025–2026

Side Effects & Cautions

  • GI: Nausea (12–18%), diarrhoea (12–17%), constipation, vomiting
  • GI events generally milder than pure GLP-1 RAs at comparable efficacy
  • ↓ Appetite (17–20%)
  • Hypoglycaemia low as monotherapy; ↑ with SU/insulin
  • No completed CVOT yet — prescribe on basis of metabolic benefit
  • UK: NICE appraised for T2DM; not yet for obesity (as Mounjaro)
Zepbound®
tirzepatide (obesity indication)
Once Weekly Obesity S/C Dual Agonist
ManufacturerEli Lilly
Max Dose15 mg weekly
First Approved2023 (FDA)

Dosing

Starting dose2.5 mg weekly × 4 weeks
Escalation↑ by 2.5 mg every 4 weeks
Maintenance range5 / 10 / 15 mg weekly
IndicationBMI ≥30, or ≥27 + comorbidity

Efficacy — SURMOUNT Programme

Mean weight loss (15 mg)−22.5% at 72 weeks (SURMOUNT-1)
≥5% responders~96%
≥10% responders~84%
≥20% responders~57%
📋 SURMOUNT-1 (without T2D) 📋 SURMOUNT-2 (with T2D) 📋 SURMOUNT-3 (intensive lifestyle) 📋 SURMOUNT-4 (withdrawal design) 📋 SURMOUNT-OSA (obstructive sleep apnoea)
SURMOUNT-2 (T2D)−14.7% weight loss + HbA1c −2.1%
OSA benefit~50% AHI reduction (SURMOUNT-OSA)

Side Effects & Practical Notes

  • GI profile similar to Mounjaro — nausea, diarrhoea, constipation
  • Greater absolute weight loss → monitor for: gallstones, nutritional deficiency, lean mass loss
  • Counsel on protein intake (≥1.2 g/kg/day) and resistance exercise
  • Not yet NICE appraised for UK obesity indication (as of early 2026)
  • FDA only currently; EMA obesity approval pending under different brand
  • Same molecule as Mounjaro — branded differently for obesity vs T2D
🔗

Fixed-Ratio Combinations (GLP-1 RA + Basal Insulin)

Simplifying injectable intensification
Xultophy®
insulin degludec + liraglutide (iDegLira)
Once Daily T2DM S/C Combo
ManufacturerNovo Nordisk
Ratio1 unit degludec : 0.036 mg liraglutide
First Approved2014 (EMA) / 2016 (FDA)

Dosing

Starting dose10 dose-steps OD (if GLP-1 RA naïve)
Starting (on basal)16 dose-steps OD
Dose range10–50 dose-steps
At 50 dose-steps= 50 U degludec + 1.8 mg liraglutide
TitrationAdjust by 2 dose-steps twice weekly (based on FPG)
AdministrationAny time of day, with or without food

Efficacy

HbA1c reduction−1.5 to −1.9%
Weight changeNeutral to −2.7 kg (vs basal insulin)
📋 DUAL programme (I–IX)
Key advantageHbA1c similar to basal-bolus with less hypos & no weight gain
vs basal-bolusDUAL VII: non-inferior HbA1c, ↓ hypo, ↓ weight

Practical Considerations

  • Simplifies intensification (single injection vs separate basal + GLP-1 RA)
  • Capped liraglutide at 1.8 mg limits GI side effects
  • If >50 dose-steps needed, consider separate components
  • GI SEs less common than liraglutide alone (gradual uptitration)
  • Cannot combine with other insulin or GLP-1 RA products
  • UK NICE: Available but not specifically appraised via TA
Suliqua® / Soliqua®
insulin glargine + lixisenatide (iGlarLixi)
Once Daily T2DM S/C Combo
ManufacturerSanofi
Two Pens10-40 & 30-60 dose ranges
First Approved2016 (EMA) / 2017 (FDA)

Dosing

Pen A (yellow)10–40 U glargine / 5–20 µg lixisenatide
Pen B (green)30–60 U glargine / 10–20 µg lixisenatide
Starting (GLP-1 RA naïve)Pen A: 10 dose-steps; Pen B: 30 dose-steps
Administration60 min before first meal of the day
TitrationAdjust by 2–4 units every week based on FPG

Efficacy

HbA1c reduction−1.1 to −1.6%
Weight changeNeutral to −0.7 kg
📋 LixiLan-O 📋 LixiLan-L
PPG controlLixisenatide component primarily targets PPG
vs basal insulinSuperior HbA1c, less weight gain, better PPG

Practical Considerations

  • Must be injected within 1 hr before first meal (lixisenatide requirement)
  • Two pen options can be confusing — ensure correct pen prescribed
  • Less GI SEs than standalone GLP-1 RA (capped lixisenatide dose)
  • Good option for patients on basal insulin needing PPG coverage
  • Lower weight loss potential vs Xultophy (liraglutide > lixisenatide for weight)