GLP-1 and GIP in Type 1 Diabetes — Evidence-Graded FAQ

Section 1 — The basics

What are GLP-1 and GIP?

GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are incretin hormones released from the gut after meals. They stimulate insulin secretion where beta-cell function remains, suppress glucagon, slow gastric emptying, and reduce appetite. The medicines in this class include GLP-1 receptor agonists (liraglutide, semaglutide, dulaglutide, exenatide), dual GLP-1/GIP agonists (tirzepatide), and triple agonists (currently in trials).

Are these medicines licensed for type 1 diabetes?

No. None of these medicines are currently licensed for type 1 diabetes. All use is off-label. Expert groups including ISPAD 2024 stress caution in paediatric and adolescent populations and explicitly call for new RCTs before wider use in young people.

How do GLP-1 therapies work in the context of T1D physiology?

In type 1 diabetes, insulin is delivered subcutaneously rather than directly into the portal circulation — meaning less insulin reaches the liver via the portal vein, which tends to produce higher glucagon levels and greater liver glucose release than in physiological insulin secretion. GLP-1 therapies can help by suppressing postprandial glucagon, slowing gastric emptying, reducing appetite, and lowering total insulin requirements. The result, in trials, is smoother postprandial glucose, lower insulin doses, and meaningful weight loss — though responses vary considerably between individuals.

Section 2 — The clinical trial evidence

The evidence base in T1D is anchored on Professor Viral Shah’s clinical trial portfolio plus the foundational ADJUNCT trials.

The headline trials

• ADJUNCT ONE — Mathieu et al., Diabetes Care 2016. Liraglutide 0.6/1.2/1.8 mg + insulin vs placebo in 1,398 adults with T1D, 52 weeks. Modest HbA1c reduction, weight loss, lower insulin requirement, dose-related symptomatic hypoglycaemia and ketosis at 1.8 mg. Grade A. PMID: 27506222
• ADJUNCT TWO — Ahrén et al., Diabetes Care 2016. Liraglutide + capped insulin in 835 adults, 26 weeks. HbA1c -0.33%/-0.22%/-0.23% vs +0.01%; weight -5.1/-4.0/-2.5 kg; clear dose-response. Grade A. PMID: 27493132
• ADJUST-T1D — Shah et al., NEJM Evidence 2025. Semaglutide titrated weekly + AID in 72 adults with T1D and obesity, 26 weeks. 36% met the composite (TIR>70% + TBR<4% + ≥5% weight loss) vs 0% placebo. HbA1c -0.3%; TIR +8.8 pp; weight -8.8 kg; insulin -22.3 U/day; no DKA. The first AID-era RCT. Grade A. PMID: 40550013
• Semaglutide + AID crossover — Nature Medicine 2025. Improved glycaemia vs placebo, but recurrent euglycaemic ketosis (no acidosis). Grade A. PMID: 39794615
• Tirzepatide observational cohort — Shah et al., JDST 2024 / 2025. 26 adults, 8 months. HbA1c -0.59%; TIR +12.6%; weight -10.5%; insulin -18.9 U/day; no DKA; peroneal palsy with rapid weight loss. The largest dataset on tirzepatide in T1D — promising, but RCT-free. Grade C. PMID: 38317405
• ADJUNCT post-hoc discontinuation — Shah et al., JDST 2024. Predictors of intolerance: lower BMI, longer T1D duration, low or absent C-peptide. ADJUNCT protocols lacked dose de-escalation, likely exaggerating dropout. Foundational for individualised stratification. Grade B. PMID: 39717993
• Genetic obesity GLP-1RA — Shah et al., JDST 2025. Mutation+ subgroup had smaller response (HbA1c -0.28% vs -0.43%; weight -5.75 kg vs -8.65 kg; 36.4% vs 80% met goals). Biology may limit drug-class response in monogenic obesity. Grade C.

What do expert guidelines say?

• ADA Standards of Care 2025/2026, Section 9 — adult-only guidance. Start low, titrate monthly; reduce insulin cautiously (10-20%); do not stop basal; monitor renal, LFTs, B12, vitamin D. Grade A. PMID: 39651989
• ADA/EASD adult T1D consensus 2021 — the definitive adult T1D framework. Adjunct therapy section covers GLP-1RAs and SGLT2 inhibitors with cautious individualised positioning. Grade A. PMID: 34590174
• ISPAD 2024 (Adjunctive Therapies, Cengiz, Danne, Ng et al.) — GLP-1RAs are NOT licensed for paediatric T1D. Off-label use only with lowest dose, slow titration, and ketone education. Urgent need for paediatric RCTs explicitly stated. Grade A consensus; paediatric T1D evidence base is Grade D by absence. PMID: 39884261
• DTS GLP-1RA + AID Consensus 2025 — first dedicated panel guidance on combining GLP-1RA with AID. Practical insulin-adjustment heuristics by AID system. Grade B. PMID: 39517127
• ATTD 2024 position — specialist-led, monthly titration, frequent ketone checks if insulin reduced. Tirzepatide promising but unlicensed. Grade B.

Section 3 — Insulin reduction: individualised, not 30% for everyone

How much does insulin typically need reducing when starting a GLP-1?

The single most important practical principle: insulin reduction must be individualised. These are starting bands used in specialist practice — they are starting points for discussion with the care team, not prescriptions:

• HbA1c above 9.0% or time in range below 40%: reduction of approximately 10%.
• HbA1c 7.5-9.0% or time in range 40-60%: reduction of approximately 20%.
• HbA1c below 7.5% or time in range above 60%: reduction of up to approximately 30%.
• High hypoglycaemia risk (time below range above 4%): approximately 30% with close CGM monitoring.

The algorithm: smallest reduction compatible with baseline risk → CGM review every one to two weeks → iterate.

How should the reduction be applied across different regimens?

• MDI or standard pump (50:50 basal:bolus): reduce basal, carb ratios, and corrections equally.
• Basal-heavy regimen (~75% basal): basal -20%; bolus, carb ratio and corrections relaxed by ~40%.
• Bolus-heavy regimen (~70-75% bolus): bolus -20%; basal -40%.
• Tandem t:slim X2: program multiple personal profiles (-10%, -20%, -30%, -40%) and step through them as the effect establishes.
• Omnipod 5, CamAPS FX: relax carb ratios and start with higher glucose targets.
• Medtronic MiniMed 780G: extend Active Insulin Time and start with a higher target.
• iLet Bionic Pancreas: raise the glucose target initially, or as a workaround enter 20-40% fewer carbs until the algorithm adapts.
• Fallback for any system: reduce carb entries by 20-40%.

See the Automated Insulin Delivery Systems Guide for system-specific detail.

Section 4 — The four safety pillars

1. Ketosis and DKA

Higher ketosis was seen at 1.8 mg liraglutide in ADJUNCT. Recurrent euglycaemic ketosis without acidosis was reported in the semaglutide + AID crossover. No DKA in ADJUST-T1D or in the tirzepatide cohort. Mitigation:

• Never stop basal insulin.
• Maintain home ketone monitoring capability.
• Avoid rapid over-reduction of insulin.
• Check ketones if glucose rises with nausea or reduced food intake.

2. Hypoglycaemia

Driven by aggressive insulin reduction, not by GLP-1RA itself. Use CGM with alerts enabled throughout titration. On AID systems, start with higher glucose targets and lower them gradually as the effect establishes.

3. Lean mass and bone

Appetite suppression and reduced food intake can drive loss of muscle mass and possibly long-term effects on bone. T1D itself is associated with reduced bone mineral density and increased fracture risk. Adolescents are a particular concern because the skeleton is still developing — long-term data are lacking. Protect with:

• Protein approximately 1.5 g per kg body weight per day, split across three to four meals.
• Resistance training two to four sessions per week.
• Vitamin D, iron and B12 monitoring.
• Consider bone monitoring in long-term therapy, particularly in younger people.

4. Rare neuromuscular events

Peroneal palsy was reported with rapid weight loss in the tirzepatide observational cohort. The takeaway is to avoid the temptation to push doses rapidly.

Section 5 — Lifestyle, nutrition and exercise

Why is resistance training relevant?

Resistance training helps preserve lean mass during GLP-1-induced weight loss. Two to four sessions per week, combining compound movements and bodyweight work, is a commonly cited target. The Exercise and T1D Practical Guide covers this in full.

How should diet adapt during titration?

Smaller, more frequent meals tend to reduce nausea in the early titration period. Heavy, fatty meals are generally better avoided initially. Spreading protein intake evenly across the day supports lean mass preservation.

How much protein is generally recommended?

A target of approximately 1.5 g per kg of body weight per day, split across three to four meals. Lean meats, fish, eggs, beans, lentils, dairy and soy are commonly prioritised sources. See Overcoming Insulin Resistance in T1D for the role of protein and resistance training together.

How are nutritional deficiencies avoided when appetite is reduced?

Prioritise nutrient-dense foods (lean protein, colourful vegetables, whole grains, nuts, seeds), use lower-fibre vegetables if fullness is an issue, consider a multivitamin and mineral supplement, and check laboratory markers (renal function, liver function, vitamin D, iron, B12) regularly.

Section 6 — Common questions

Is there benefit for people who are not overweight?

Possible benefits include glucagon suppression, smoother postprandial glucose, and reduced insulin requirements, even without a weight-loss goal. However, the risk of GI side effects becomes proportionally more important without a weight-loss benefit, and lean mass protection becomes a more prominent priority. The guidance is to use the minimum effective dose and discuss this context carefully with the diabetes care team.

Will a GLP-1 replace insulin in type 1 diabetes?

No. Insulin remains essential in type 1 diabetes. GLP-1 therapies reduce the amount of insulin needed — they do not remove the requirement for it. Basal insulin must not be stopped.

How does this relate to insulin resistance in type 1 diabetes?

GLP-1 therapies may reduce insulin resistance through their effects on weight, glucagon, and satiety. See Overcoming Insulin Resistance in T1D, the Eight Causes of Insulin Resistance, and Seven Ways to Improve Insulin Sensitivity.

What are the common side effects?

Gastrointestinal effects — nausea, vomiting, diarrhoea — are the most frequently reported, particularly in the early titration period. Appetite suppression can lead to undernutrition if diet is not well managed. Loss of lean mass can occur if resistance training and protein intake are not maintained. Peroneal palsy has been reported rarely with very rapid weight loss.

How is nausea typically managed?

Starting at the lowest dose and titrating slowly (monthly) is the most consistent approach across guidelines. Small, frequent meals, avoiding heavy, fatty food at initiation, and moderate fibre intake early on tend to reduce nausea severity.

Related GNL resources

• Episode 17 — GLP-1 in T1D with Professor Viral Shah
• Downloadable PDF FAQ (10 September 2025)
• Overcoming Insulin Resistance in T1D
• Eight Causes of Insulin Resistance in T1D
• Episode 14 — T1D and Insulin Resistance
• Seven Ways to Improve Insulin Sensitivity
• Exercise and T1D Practical Guide
• Automated Insulin Delivery Systems Guide
• Continuous Glucose Monitoring Guide