GLP-1 Therapies in Type 1 Diabetes FAQ

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 stomach emptying, and reduce appetite. Medicines in this class include GLP-1 receptor agonists (liraglutide, semaglutide, dulaglutide, exenatide), dual GLP-1/GIP agonists (tirzepatide), and triple agonists targeting GLP-1, GIP, and glucagon receptors simultaneously, which are currently in clinical 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 stress caution in paediatric and adolescent populations and call for new trials 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 reducing glucagon, slowing gastric emptying, suppressing appetite, and in some people lowering total insulin requirements. The overall effect may be smoother post-meal glucose, lower insulin doses, and weight reduction — though responses vary considerably between individuals.

The evidence

What do the main clinical trials show in type 1 diabetes?

• ADJUNCT ONE (liraglutide, 52-week RCT): modest HbA1c reduction, weight loss, lower insulin requirements — but increased hypoglycaemia and ketosis at higher doses. PMID: 27506222
• ADJUNCT TWO (liraglutide with capped insulin, 26-week RCT): HbA1c −0.3%, weight −5 kg, lower insulin, increased hypoglycaemia at 1.2 mg and increased ketosis at 1.8 mg. PMID: 27493132
• ADJUST-T1D (semaglutide plus AID system, NEJM Evidence 2025, 26-week RCT): no DKA; HbA1c −0.3%, time in range +9%, weight −8.8 kg, insulin −22 U/day. PMID: 40550013
• Semaglutide crossover (Nature Medicine 2025): improved glucose, but recurrent euglycaemic ketosis observed. PMID: 39794615
• Tirzepatide observational study (JDST 2025): HbA1c −0.6%, time in range +12%, weight −10%, insulin −19 U/day; no DKA reported. PMID: 38317405

What do expert guidelines say?

• ADA/EASD Consensus 2021: off-label use should be specialist-led, starting with the lowest dose and titrating monthly, with cautious insulin reduction. PMID: 34590174
• ADA Standards of Care 2025: regular CGM review and laboratory monitoring (renal, liver function, B12, vitamin D). PMID: 39651989
• ISPAD 2024 (youth): GLP-1 therapies are only licensed for obesity and type 2 diabetes in those aged 10 and over, not for type 1 diabetes; where used off-label, lowest dose, slow titration, and ketone education are emphasised. PMID: 39884261
• DTS GLP-1RA plus AID Consensus 2025: start low, go slow; specialist-led only; registry data essential. PMID: 39517127

Insulin adjustments

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

These are the starting bands used in specialist practice — they are starting points for discussion with the care team, not prescriptions:

• HbA1c above 9% or time in range below 40%: reduction of approximately 10%.
• HbA1c 7.5–9% 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.

What tends to happen on MDI?

Both basal and bolus insulin are typically reduced proportionally. Insulin-to-carb ratios and correction factors are often relaxed slightly. Close CGM monitoring throughout titration is consistently recommended across guidelines.

What tends to happen on pump or AID systems?

See the Automated Insulin Delivery (AID) Systems Guide for system-specific detail. In general, basal targets tend to be reduced more than bolus, and higher glucose targets are used initially before stepping down as the effect is established. System-specific starting points used in practice include: on Tandem X2, creating multiple profiles (−10%, −20%, −30%); on Medtronic 780G, lengthening active insulin time and using a higher target; on Omnipod and CamAPS, relaxing carb ratios initially; on iLet, selecting “smaller meal” for usual meals until the algorithm adapts over 7–14 days.

What safety checks matter throughout?

• Basal insulin is never stopped — insulin remains essential in type 1 diabetes.
• CGM with alerts enabled throughout titration.
• Ketone testing when unwell, experiencing nausea, or with unexplained high glucose.
• Sick-day rules education before starting.

Lifestyle, nutrition, and exercise

Why is resistance training relevant?

Resistance training helps preserve lean mass, which can otherwise decline with 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 Type 1 Diabetes — Practical Guide covers this in full, including aerobic, anaerobic, and mixed sports approaches.

How does diet tend to need adapting when starting a GLP-1?

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. The Exercise Carbohydrate Calculators may be useful for those who train actively.

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, is frequently used in practice. Lean meats, fish, eggs, beans, lentils, dairy, and soy are commonly prioritised sources. See Overcoming Insulin Resistance in T1D for more on the role of protein and resistance training together.

How are nutritional deficiencies avoided when appetite is reduced?

Prioritising nutrient-dense foods, using lower-fibre vegetables if fullness is an issue, considering a multivitamin, and checking laboratory markers (renal function, liver function, vitamin D, iron, B12) regularly are all commonly recommended approaches.

What is worth knowing about bone health?

Adequate protein, vitamin D, and calcium intake support bone health during GLP-1-induced weight loss. Resistance training also provides mechanical loading that benefits bone density. Bone monitoring may be appropriate for long-term therapy, particularly in younger people.

Side effects

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 and avoiding heavy, fatty food at initiation, along with moderate fibre intake early on, tend to reduce nausea severity.

Broader questions

Is there potential benefit for people who are not overweight?

Possible benefits include glucagon suppression, smoother post-meal glucose, and reduced insulin requirements, even without a weight-loss goal. However, the risk of GI side effects tends to be greater, and lean mass protection becomes a more prominent priority. Using the lowest effective dose and discussing this context with the care team is important.

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 for the full picture.

Related GNL resources

• Episode 17 — GLP-1 in T1D (episode page)
• Overcoming insulin resistance in T1D
• Eight causes of insulin resistance in T1D
• Episode 14 — T1D and insulin resistance
• Seven ways to address insulin resistance in T1D
• Exercise and T1D — Practical Guide
• Continuous glucose monitoring (CGM) guide