Episode 17, GLP-1 in Type 1 Diabetes

Why this episode exists

If you live with type 1 diabetes, you already do the work that insulin alone cannot quite finish. You count carbohydrates, you correct, you watch the post-meal climb, and over the years you may notice that the doses creep up while the body holds on to more weight. None of that is a failure of effort; it is a structural feature of replacing one hormone when the healthy body uses several.

This episode exists to take that lived experience seriously and ask what the evidence says about adding a second hormone to the picture. GLP-1 receptor agonists are emerging as a potential first step towards a true multi-hormone approach, and one key theme runs through the conversation: it may be time for type 1 diabetes care to move beyond insulin alone.

In this episode

John and Professor Shah open with why insulin alone has structural limitations in type 1 diabetes, work through how GLP-1 therapies act on the body, and then walk the trial evidence from the early exenatide and liraglutide studies to the more recent semaglutide and tirzepatide data. They close on what the literature tends to show at a population level, the practical considerations around monitoring and nutrition, and where the field is heading next.

Professor Shah co-authored the consensus guidance on the safe off-label use of these therapies in type 1 diabetes, so the conversation stays close to what the evidence supports rather than ahead of it.

Watch or listen

Key themes

Why insulin alone has structural limitations

The episode opens by exploring why insulin alone has structural limitations in type 1 diabetes. Injected insulin reaches the periphery before the portal vein, which tends to drive insulin resistance over time. Higher insulin levels promote weight gain and metabolic stress, while low portal insulin and high glucagon tend to produce post-meal hyperglycaemia and increased insulin requirements. The result is a self-reinforcing cycle: higher insulin doses can lead to more weight gain, which in turn makes management harder. For the wider picture, the GNL guide on overcoming insulin resistance in T1D sits alongside this conversation.

How GLP-1 therapies work, the mechanism

GLP-1 receptor agonists work through several complementary mechanisms. They delay gastric emptying, which tends to reduce post-meal glucose spikes. They increase satiety signals, leading to reduced food intake on average. They suppress glucagon, which improves post-meal stability. And they may offer potential support for any residual insulin secretion, which is C-peptide dependent.

The evidence in type 1 diabetes

The trial picture builds in stages. Exenatide and liraglutide were the early studies, showing modest benefit in type 1 diabetes. The more recent semaglutide trials (ADJUST T1D) reported up to 30% insulin dose reduction alongside weight loss and improved time in range. Tirzepatide observational data showed similar patterns in real-world use. Professor Shah co-authored the consensus guidelines on safe off-label use that sit on top of this evidence base.

What the evidence tends to show

The following reflects what current evidence tends to show at a population level. Individual responses vary significantly and this is worth exploring with a diabetes care team.

On insulin adjustment, studies suggest targeting around a 30% reduction in insulin doses as a starting point, with slow titration and close monitoring; individual adjustment is essential, and basal and bolus requirements may both change, in different proportions depending on the therapy used. On monitoring, CGM is described as critical during GLP-1 initiation, with adjustments based on CGM data helping to identify how individual glucose patterns are changing, and starting HbA1c influencing how aggressively monitoring is needed early on. On nutrition, because GLP-1 therapies reduce appetite significantly, ensuring adequate protein intake (discussed in the evidence as approximately 1.5 g per kg) to preserve muscle mass is a practical consideration; resistance training alongside is often recommended, and multivitamin and mineral support may be worth discussing if appetite falls substantially.

Future directions

Triple and quadruple agonist agents are in development and may offer further metabolic benefits. Reimbursement remains a challenge: the evidence base is growing but large randomised controlled trials in type 1 diabetes remain limited. On paediatric potential, these therapies are currently approved in type 2 diabetes from age 12, and the evidence picture in type 1 diabetes is evolving.

Practical exploration

What follows reflects what the evidence tends to show at a population level. Individual responses vary significantly, and any decision about starting, adjusting, or stopping a therapy belongs with your diabetes care team.

For people living with type 1 diabetes and their families

• If weight gain and creeping insulin doses are part of your experience, the structural reasons in this episode may be worth raising with your care team. They are a feature of insulin replacement, not a personal failing.
• GLP-1 therapies for type 1 diabetes remain off-label in most settings. The companion FAQ sets out the evidence grades and the safety pillars so you can explore the picture with your team.
• Where these therapies are used, the evidence discusses slow titration, close monitoring with CGM, and attention to protein intake and muscle mass; these are conversations to have, not steps to take alone.

For clinicians and educators

• The consensus guidance Professor Shah co-authored frames safe off-label use; the FAQ pack layers AID-system-specific adjustment heuristics and individualised insulin reduction bands by HbA1c, TIR, and TBR on top.
• CGM is described as critical during initiation, with starting HbA1c shaping how aggressively early monitoring is needed.
• The four safety pillars (ketosis, hypoglycaemia, lean mass and bone, and rare neuromuscular events) are the structure the evidence pack uses to keep the conversation grounded.

About the guest

Professor Viral Shah MD is Professor of Medicine and Director of Diabetes Clinical Research, Center for Diabetes and Metabolic Diseases, IU School of Medicine. He is author of multiple clinical trials and consensus guidelines on GLP-1 therapies in type 1 diabetes.

Host: John Pemberton, The Glucose Never Lies.

Evidence references

• ADJUNCT ONE, PMID 27506222
• ADJUNCT TWO, PMID 27493132
• ADJUST T1D, PMID 40550013
• Semaglutide crossover study, PMID 39794615
• Tirzepatide observational data (Shah 2024), PMC11571402
• Shah discontinuation post-hoc (ADJUNCT I/II), PMID 39717993
• Shah 2025, GLP-1RA / tirzepatide in T1D with severe early (genetic) obesity (JDST)
• Insulin titration paper, PMID 39829697
• Adjunct therapy review, PMID 40618954
• Bone health review, PMC8118128
• Weight loss and bone, PMID 38916894

Consensus and guidelines:

• ADA Standards 2025, PMID 39651989
• ISPAD 2024, PMID 39657603
• GLP-1 AID consensus, PMID 39517127

Related reading on GNL

This Episode 17 conversation was the inspiration for the four-part Adjunctive Therapies guide built on top of the April 2026 evidence update.