American Diabetes Association · Standards of Care · January 2026

GLP-1 Receptor Agonists
2026 Clinical Guidance

A comprehensive visual guide to the ADA 2026 evidence-based recommendations for glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes and obesity management

📋 Section 9 · Pharmacologic Treatment ✅ Section 8 · Obesity Management ❤️ Section 10 · Cardiovascular Risk 🫘 Section 11 · Kidney Disease 🎯 Person-Centred Approach 🆕 New 2026 Updates
15%
A1C REDUCTION
Average A1C reduction with semaglutide
20%
MACE RISK ↓
CV event reduction (semaglutide SUSTAIN-6)
−22%
BODY WEIGHT
Tirzepatide SURMOUNT-1 at max dose
1st
LINE PREFERRED
Alongside SGLT2i in high CV risk
↑ T1D
NEW 2026
GLP-1 RA now adjunct in T1D + obesity
Pharmacology
Mechanism of Action

GLP-1 receptor agonists mimic endogenous incretins to achieve pleiotropic metabolic benefits through multiple pathways.

🔬

Pancreatic β-Cells

Glucose-dependent insulin secretion — lowers risk of hypoglycaemia. Stimulates insulin synthesis and β-cell proliferation.

🧠

Hypothalamus / CNS

Reduces appetite and food intake via central GLP-1R signalling. Promotes satiety, decreases hedonic eating.

🫀

Cardiovascular System

Reduces MACE, atherosclerosis progression, inflammation and oxidative stress. Improves endothelial function.

🫘

Kidneys

Reduces albuminuria and slows CKD progression. New 2026: initiation/continuation on dialysis to reduce CV risk.

🍔

GI Tract

Slows gastric emptying — blunts post-prandial glucose excursions. Reduces glucagon secretion from α-cells.

🩺

Liver (MASLD/MASH)

NEW 2026: GLP-1 RA with proven MASH benefit preferred in T2D + biopsy-proven MASH or high fibrosis risk.

🧫

Pancreatic α-Cells

Suppresses glucagon secretion in a glucose-dependent manner. Reduces fasting and post-prandial hyperglucagonaemia.

🦴

Cognition / Neuro

Emerging 2026 evidence: GLP-1 RA may slow cognitive decline in older adults with T2D (diabetes-related dementia).

Evidence-Based Clinical Recommendations
ADA 2026 GLP-1 RA Key Recommendations

Each recommendation is graded by level of evidence. Grade A = clear evidence from well-conducted RCTs or meta-analyses.

REC 9.7 Grade A

ASCVD / High CV Risk — First-Line Cardiometabolic Protection

In adults with T2D and established or high risk of ASCVD, include a GLP-1 RA and/or SGLT2i in the treatment plan for glycaemic management AND comprehensive CV risk reduction — irrespective of A1C level.

REC 8.18 Grade A

Obesity Pharmacotherapy — Preferred Agents

In T2D with overweight/obesity, the preferred pharmacotherapy is a GLP-1 RA or dual GIP/GLP-1 RA with greater weight loss efficacy (i.e., semaglutide or tirzepatide), especially considering their weight-independent benefits.

REC 4.27a Grade A 🆕 Updated

MASLD/MASH — Preferred Glycaemic Agent

In T2D with biopsy-proven MASH or high risk for liver fibrosis (noninvasive tests), a GLP-1 RA is preferred for glycaemic management due to beneficial effects on MASH histology.

REC 4.26 Grade A 🆕 Updated

MASLD + Obesity — Consider GLP-1 RA for Weight

In T2D + MASLD + overweight/obesity, consider a GLP-1 RA with demonstrated MASH benefit, or dual GIP/GLP-1 RA with potential MASH benefit, as adjunctive therapy to lifestyle intervention.

REC 9.6 Grade A

Combination Therapy — Shorten Time to Goal

Consider combination therapy in adults with T2D for initial treatment to shorten time to attainment of individualised glycaemic goals. GLP-1 RA + metformin is a robust initial combination.

REC 9.5 Grade E

Person-Centred Treatment Selection

Use medications providing sufficient effectiveness to achieve treatment goals, with consideration of CV/kidney/weight effects, hypoglycaemia risk, cost and access, adverse reactions/tolerability, and individual preferences.

CKD REC Grade A 🆕 NEW 2026

CKD / Dialysis — GLP-1 RA for CV Risk Reduction

New 2026: Guidance added for initiation or continuation of GLP-1–based therapy in individuals on dialysis to reduce cardiovascular risk. Previously, dialysis patients were excluded from this guidance.

T1D + OBESITY Grade B 🆕 NEW 2026

Type 1 Diabetes + Obesity — GLP-1 RA as Adjunct

New 2026: GLP-1 receptor agonists and metabolic surgery are now recommended as adjunctive therapies in T1D with obesity, alongside insulin management.

HF REC Grade B

Symptomatic Heart Failure

GLP-1 or dual GIP/GLP-1 receptor agonists supported when evidence shows benefit. Recommendations specifically address symptomatic HF management with GLP-1 RA consideration.

PREGNANCY REC Grade E 🆕 Updated

Pregnancy — Discontinue GLP-1 RA

Updated 2026: Discontinue GLP-1 RA and dual GIP/GLP-1 therapy before attempting conception. These agents are not recommended during pregnancy due to insufficient safety data.

REC 4.27b Grade B

MASH — GLP-1 RA + Pioglitazone Combination

Combination therapy with pioglitazone + GLP-1 RA can be considered for hyperglycaemia in T2D with biopsy-proven MASH or high fibrosis risk due to potential beneficial effects on MASH.

DOSING 2026 Grade A 🆕 Emphasis

Individualised Dosing & Titration

New emphasis 2026: Obesity pharmacotherapy recommendations stress individualised dosing and titration to optimise efficacy, minimise adverse effects, and enhance medication adherence.

Clinical Decision Support
GLP-1 RA Prescribing Algorithm

ADA 2026 person-centred framework for initiating and optimising GLP-1 RA therapy in T2D

NEWLY DIAGNOSED T2D or EXISTING T2D REQUIRING TREATMENT OPTIMISATION
STEP 1: Comprehensive Assessment
A1C · Weight/BMI · CV risk (ASCVD/HF) · Kidney function (eGFR/ACR) · Liver status (MASLD) · Hypoglycaemia risk · Cost & access · Patient preference · Pregnancy status
↓ ASSESS COMORBIDITY PROFILE ↓
🫀 CV Disease / High CV Risk

GLP-1 RA +/or SGLT2i
Irrespective of A1C
Preferred: semaglutide, liraglutide, dulaglutide

Grade A · Preferred
⚖️ Obesity / Weight Loss Priority

Semaglutide 2.4mg SC or Tirzepatide
Max dose for max efficacy
Individualised titration 2026

Grade A · Preferred
🫘 CKD / Kidney Protection

GLP-1 RA + SGLT2i
Continue even on dialysis
New 2026: dialysis inclusion

Grade A · Consider
STEP 2: Choose GLP-1 RA Agent
Match to patient profile: injection frequency preference · Oral vs SC · Proven CV benefit required? · MASH treatment needed? · Insurance/cost/access considerations
💊 Oral Preference

Oral semaglutide 3–14mg OD
Taken 30 min before first meal
Moderate A1C reduction

💉 Weekly Injection

Semaglutide SC 0.5–2mg
Dulaglutide 0.75–4.5mg
Tirzepatide 2.5–15mg

💉 Daily Injection

Liraglutide 0.6–1.8mg OD
Exenatide 5–10mcg BD
MASH: liraglutide/semaglutide

STEP 3: Initiate at Low Dose — Titrate Gradually
2026 emphasis: individualised dosing & titration · Slow up-titration reduces GI adverse effects · Titrate to therapeutic dose for maximum benefit
STEP 4: Review at 3–6 Months
A1C goal achieved? · ≥5% weight loss? · CV/kidney markers improved? · Tolerability acceptable? · Consider dose escalation or add-on therapy
✅ Goals Met

Continue current regimen · Annual review · CGM if appropriate · Reinforce lifestyle

Continue
⚠️ Partial Response

Intensify dose to maximum tolerated · Add SGLT2i if not already · Address adherence

Intensify
❌ Inadequate / Intolerant

Switch agent within class · Consider tirzepatide · Refer for bariatric surgery if BMI criteria

Switch / Escalate
Pharmacotherapy Comparison
GLP-1 RA & GIP/GLP-1 Agents — 2026 Overview

Comparison of licensed agents relevant to ADA 2026 recommendations. *UK NHS availability may differ — refer to local formulary and NICE guidance.

Agent Class Route / Frequency A1C Reduction Weight Loss CV Outcome Trial MASH Benefit ADA 2026 Role
Semaglutide SC
Ozempic® / Wegovy®
GLP-1 RA SC weekly 1.5–2.0% 5–15% (DM); up to 15% (Wegovy) SUSTAIN-6 / SELECT (+20% MACE ↓) Yes — NASH studies positive Preferred — CV & Obesity
Tirzepatide
Mounjaro® / Zepbound®
Dual GIP/GLP-1 RA SC weekly 2.0–2.5% 15–22% (SURMOUNT-1) SURPASS-CVOT (pending full data) Potential — MASH studies ongoing Preferred — Max Weight Loss
Oral Semaglutide
Rybelsus®
GLP-1 RA Oral daily 1.0–1.4% 2–4% PIONEER-6 (non-inferior) Limited data Consider — Injection-averse
Liraglutide
Victoza® / Saxenda®
GLP-1 RA SC daily 1.0–1.5% 3–8% LEADER (13% MACE ↓) Yes — LEAN trial (NASH benefit) Consider — Proven CV + MASH
Dulaglutide
Trulicity®
GLP-1 RA SC weekly 1.0–1.6% 2–4% REWIND (12% MACE ↓) Limited data Consider — Weekly, auto-inject device
Exenatide QW
Bydureon BCise®
GLP-1 RA SC weekly 0.9–1.3% 2–3% EXSCEL (neutral) Not established Alternative
Exenatide BD
Byetta®
GLP-1 RA SC twice daily 0.8–1.1% 1–3% No CV outcome trial Not established Less preferred

† Refer to manufacturer's prescribing information for full dosing. Data summarised from major CVOTs and clinical trials. ADA 2026 does not endorse specific brands.

Clinical Evidence Summary
Efficacy & Outcomes Data

Visual representation of key trial outcomes supporting ADA 2026 recommendations for GLP-1 RA use.

Mean Body Weight Reduction
% body weight lost in pivotal trials (maximum approved doses)
Tirzepatide
–22%
Sema 2.4mg
–15.5%
Dulaglutide
–4.2%
Liraglutide
–8%
Exenatide QW
–2.9%
Mean A1C Reduction from Baseline
Approximate mean A1C (%) reduction — from RCT evidence
Tirzepatide
–2.5%
Sema SC
–2.0%
Liraglutide
–1.5%
Dulaglutide
–1.6%
Oral Sema
–1.4%
MACE Risk Reduction (CVOTs)
% reduction in major adverse cardiovascular events vs placebo
Semaglutide (SUSTAIN-6)–26%
Liraglutide (LEADER)–13%
Dulaglutide (REWIND)–12%
Semaglutide (SELECT — non-DM)–20%
Exenatide QW (EXSCEL)–9% (NS)
Key Pleiotropic Benefits Hierarchy
Strength of evidence for non-glycaemic benefits (ADA 2026 framework)
ASCVD/MACE ReductionVery High
Body Weight ReductionVery High
MASH Histological BenefitHigh
Kidney ProtectionModerate–High
Cognitive BenefitEmerging
Comorbidity-Guided Prescribing
GLP-1 RA in Specific Clinical Contexts

ADA 2026 comorbidity-guided guidance — matching the right therapy to the right patient profile.

🫀

Established ASCVD / High CV Risk

GLP-1 RA with proven MACE reduction (semaglutide, liraglutide, dulaglutide) should be included irrespective of A1C. May combine with SGLT2i for additive benefit.

Preferred · Grade A
❤️‍🩹

Heart Failure

GLP-1 or dual GIP/GLP-1 RA supported when evidence shows benefit for symptomatic HF. SGLT2i has strongest evidence for HFrEF. Consider combination. Monitor volume status.

Consider · Grade B
🫘

Chronic Kidney Disease

Continue or initiate GLP-1 RA even with advanced CKD. New 2026: Can initiate or continue on dialysis for CV risk reduction. Check agent-specific eGFR thresholds.

New 2026 · Grade A
🩺

MASLD / MASH

GLP-1 RA preferred in T2D + biopsy-proven MASH. Consider pioglitazone + GLP-1 RA combination. Refer to hepatologist if FIB-4 >2.67.

New 2026 Update · Grade A
⚖️

Obesity / Overweight

Semaglutide 2.4mg or tirzepatide preferred for maximum weight loss efficacy. Individualised dosing and titration now emphasised. Consider bariatric surgery if BMI ≥35 with complications.

Preferred · Grade A
🧠

Cognitive Impairment / Older Adults

GLP-1 RA and SGLT2i show small benefits slowing cognitive decline in T2D. New entity: 'diabetes-related dementia'. Simplified regimens preferred in frail elderly. Low hypoglycaemia risk advantageous.

Emerging Evidence
🤰

Pregnancy / Pre-Conception

Discontinue GLP-1 RA before attempting conception. Not recommended during pregnancy — insufficient safety data. Switch to insulin-based regimen when planning pregnancy.

Discontinue · Grade E
🧒

Type 1 Diabetes + Obesity

New 2026: GLP-1 RA now recognised as adjunctive therapy in T1D with obesity, alongside insulin. Also: metabolic surgery considered in eligible T1D + obesity patients.

New 2026 · Grade B
🎗️

Cancer Treatment / Hyperglycaemia

New 2026: Comprehensive guidance on glycaemic management during cancer therapy including mTOR inhibitors, PI3K inhibitors, immune checkpoint inhibitors and glucocorticoids.

New 2026 Section
💉

On Insulin — Intensification

Adding GLP-1 RA to insulin regimen reduces hypoglycaemia risk vs basal-bolus insulin. May allow insulin dose reduction. Weekly GLP-1 RA preferred for adherence.

Grade A
🦠

Compounded GLP-1 RA — ADA Warning

2026 Statement: ADA recommends against non-FDA-approved compounded GLP-1 and dual GIP/GLP-1 products due to uncertain content, safety, quality and effectiveness.

Avoid Compounded · ADA 2026
🩸

Hyperglycaemia Without Complications

Consider combination therapy from diagnosis to shorten time to glycaemic goals. GLP-1 RA + metformin well-validated. A1C-guided but comorbidity-informed choice throughout.

Consider · Grade A
Safety Profile
Adverse Effects & Contraindications

Understanding the safety profile of GLP-1 RAs is essential for person-centred prescribing decisions.

⚠️ Common Adverse Effects

  • 🤢
    Nausea (Very Common — 20–40%)Dose-dependent, usually transient. Reduced with slow titration. 2026 emphasis on gradual up-titration protocol.
  • 🚽
    Vomiting / DiarrhoeaGI effects most common in first 4–8 weeks. Taking with food and adequate hydration helps. Usually self-limiting.
  • 😮‍💨
    ConstipationParticularly with tirzepatide. Slower gastric motility effect. Ensure adequate fluid and fibre intake.
  • 💉
    Injection Site ReactionsMild redness, bruising, or nodule formation. Rotate injection sites. Less frequent with weekly agents.
  • ❤️
    Increased Heart RateMean increase of 2–4 bpm. Usually clinically non-significant. Monitor in patients with arrhythmia history.
  • 😴
    Fatigue / AstheniaTransient, usually resolves within weeks of dose stabilisation.

🚫 Contraindications & Cautions

  • 🧬 Personal or family history of medullary thyroid carcinoma
  • 🧬 Multiple Endocrine Neoplasia type 2 (MEN2)
  • 🤰 Pregnancy — discontinue before conception (ADA 2026)
  • ⚠️ Severe GI disease — gastroparesis, IBD, prior GI surgery
  • 🫘 Check agent-specific eGFR thresholds (most now have wide renal range)
  • 💊 Prior hypersensitivity to any GLP-1 RA excipient
  • 🩺 Pancreatitis history — use with caution; monitor for symptoms
  • 🧪 Gallbladder disease — increased risk of cholelithiasis
  • 💊 Drug interactions with oral medications with narrow therapeutic window (altered absorption)
  • 🏥 Perioperative — consider withholding for elective procedures (anaesthetic risk)
✅ Key Safety Advantage — ADA 2026 GLP-1 RAs carry low intrinsic hypoglycaemia risk due to glucose-dependent mechanism of action. However, when combined with insulin or sulfonylureas, hypoglycaemia risk increases. Consider dose reduction of concomitant insulin/SU when initiating GLP-1 RA. This is a significant advantage in frail or older patients.
⚠️ Pre-Operative Consideration — Emerging 2026 Guidance Growing evidence suggests GLP-1 RA-associated delayed gastric emptying may increase aspiration risk under general anaesthesia. Consider withholding weekly agents for 1 week and daily agents for 1 day before elective procedures — discuss with anaesthetic team. This is an evolving area not yet fully codified in ADA 2026 but clinically important.
UK Clinical Practice
ADA 2026 in UK Context
🇬🇧

Applying ADA 2026 GLP-1 RA Guidance in NHS/UK Practice

ADA guidelines are internationally recognised and increasingly aligned with UK practice. The DiabetesontheNet 2026 At-A-Glance noted that "most recommendations are relevant to healthcare professionals in the UK." Key UK considerations:

  • NICE NG28/TA583 guidance on semaglutide and tirzepatide — check current NICE Technology Appraisals for reimbursement criteria
  • NHS England Tier 3 weight management services — GLP-1 RA access may require tier referral pathway
  • Mounjaro (tirzepatide) — NICE TA1008 approved for T2D; Zepbound (obesity indication) — check current NHS BLUETEQ/NICE approval status
  • Wegovy (semaglutide 2.4mg) — NHS approved via specialist services; availability expanding via GP commissioning from 2025-6
  • MASH/MASLD guidance: aligns with BSG/BASL liver disease pathways; hepatology co-management recommended if FIB-4 >2.67
  • Liraglutide — Saxenda® for obesity may have restricted access on NHS; Victoza® for T2D widely available
  • Compounded GLP-1 agents: MHRA does not approve unlicensed compounded versions; ADA's warning reinforces UK regulatory position
  • CKD: aligns with NICE NG203 chronic kidney disease guidance supporting GLP-1 RA use in T2D + CKD
2026 Updates Summary
Key 2026 Changes at a Glance

Most significant new or updated GLP-1 RA-relevant recommendations versus ADA 2025.

GLP-1 RA in T1D + Obesity — NEW

First formal ADA recommendation endorsing GLP-1 RA as adjunct therapy in T1D patients with obesity, alongside insulin.

Dialysis Patients — NEW CKD Guidance

New recommendation allowing initiation or continuation of GLP-1–based therapy in CKD patients on dialysis for CV risk reduction.

MASLD/MASH — Updated Recommendation

Rec 4.26 and 4.27a updated — GLP-1 RA with demonstrated MASH benefit now explicitly preferred in T2D + biopsy-proven MASH or high fibrosis risk.

Individualised Obesity Drug Dosing

New 2026 emphasis on individualised titration to optimise efficacy, minimise AEs, and enhance adherence — especially semaglutide and tirzepatide.

Pregnancy — Pre-Conception Discontinuation

Updated guidance explicitly states GLP-1 RA and dual GIP/GLP-1 should be discontinued before attempting conception.

Cancer Hyperglycaemia — New Section

2026 introduces comprehensive glycaemic management guidance for patients on cancer therapies (immune checkpoint inhibitors, mTOR/PI3K inhibitors).

Symptomatic Heart Failure — Updated Algorithm

Updated clinical algorithm for symptomatic HF management now specifically addresses GLP-1 or dual GIP/GLP-1 RA when evidence supports benefit.

Compounded GLP-1 RA — Official ADA Statement

New ADA guidance statement formally recommending against non-FDA-approved compounded GLP-1 and dual GIP/GLP-1 products.

Prescribing Quick Reference
Dosing & Titration Summary

2026 emphasis: individualised titration is key. Slow up-titration reduces GI adverse effects and improves adherence.

SEMAGLUTIDE SC Ozempic®

Weekly SC Injection — T2D & Weight

T2D: Start 0.25mg → 0.5mg (4 weeks) → 1mg (4 weeks) → 2mg if needed

Obesity (Wegovy®): Start 0.25mg → titrate over 16 weeks to 2.4mg weekly

Inject SC abdomen, thigh or upper arm.

TIRZEPATIDE Mounjaro®

Weekly SC Injection — Dual GIP/GLP-1

Start: 2.5mg → 5mg (4 weeks) → 7.5mg → 10mg → 12.5mg → 15mg

Titrate every 4 weeks as tolerated. Maximum 15mg weekly.
Individualized dose target per ADA 2026 — not all need 15mg.

LIRAGLUTIDE Victoza®

Daily SC Injection — T2D & MASH

Start: 0.6mg OD × 1 week → 1.2mg OD → 1.8mg OD if needed

Administer any time, independent of meals.
Preferred in MASH — LEAN trial evidence.

ORAL SEMAGLUTIDE Rybelsus®

Daily Oral Tablet

Start: 3mg OD × 4 weeks → 7mg OD × 4 weeks → 14mg OD

Take on an empty stomach, ≥30 min before food/drink/other medication, with max 120mL water. Swallow whole.

DULAGLUTIDE Trulicity®

Weekly SC — Auto-Inject Pen

Start: 0.75mg weekly → 1.5mg weekly
Can increase to 3mg → 4.5mg for additional glycaemic control.

Single-use auto-injector device — no reconstitution required.

EXENATIDE QW Bydureon BCise®

Weekly SC Extended-Release

Fixed dose: 2mg SC once weekly. No titration required.
Inject abdomen, thigh or upper arm. Can inject any time, with or without food.
May see injection site nodule — normal with microspheres.

📋 ADA 2026 Dosing Principle Per ADA 2026 Standards, for obesity pharmacotherapy: "recommendations emphasise individualised dosing and titration to optimise efficacy, minimise adverse effects, and enhance medication adherence." Do not rush titration — a patient maintained on a lower dose with good tolerability may achieve better long-term outcomes than one escalated too quickly and who discontinues.
Clinical Monitoring
Ongoing Monitoring Framework
📊

Glycaemic Monitoring

A1C every 3 months until stable, then every 6 months. CGM preferred where available and clinically indicated. Target A1C individualised (typically <53mmol/mol / <7% in most adults).

⚖️

Weight Monitoring

Monthly weight review initially. Target ≥5% body weight loss at 16 weeks as indicator of response. If <5% at max tolerated dose, reassess and consider switching or escalating.

🫘

Renal Function

eGFR and ACR at least annually. Monitor for eGFR decline when adding medications. GLP-1 RA can continue in most stages of CKD — check agent-specific SPC for thresholds.

🩺

Liver Function (MASLD)

FIB-4 calculation at baseline and annually. If FIB-4 >2.67 — refer hepatology. Liver function tests + fibroscan where indicated. GLP-1 RA response in MASH: reassess histology at 1 year if biopsy-proven.

❤️

Cardiovascular Review

Blood pressure, lipid profile, resting ECG where indicated. Monitor heart rate. ASCVD risk score annually (QRISK3 in UK). Optimise all CV risk factors concurrently.

📋

Medication Review

Review concomitant insulin/SU doses when initiating GLP-1 RA — reduce to prevent hypoglycaemia. Check drug interactions (especially narrow TI oral medications). Annual medication reconciliation.