The insulin-alone problem

Insulin is, and remains, essential in type 1 diabetes. Nothing on the horizon changes that. But insulin on its own does not replicate the full endocrine response that the pancreas delivers in people without T1D, and for a subset of adults it leaves three problems stubbornly unsolved.

1. Stubborn postprandial rises. Even with well-timed bolus insulin, some meals spike harder than the algorithm can keep up with. Appetite cues continue to drive eating after the meal is physiologically done.
2. Rising total daily insulin requirement. Some people slowly need more insulin year on year. Insulin resistance creeps upward; basal rates climb; the dose feels like it is chasing the person rather than matching them.
3. Weight gain that the insulin itself drives. Insulin is anabolic. The more of it you use, the more its weight-gain and lipogenic effects show up. Weight up, insulin resistance up, insulin requirement up, weight up further. The loop is well described and hard to break from inside insulin alone.

Adjunctive therapy is the name for medicines added alongside insulin that target the biology outside insulin’s reach. GLP-1 receptor agonists (GLP-1RA, such as liraglutide and semaglutide) and dual GLP-1/GIP agonists (tirzepatide) are the adjuncts with the strongest modern evidence base in T1D, and the focus of Parts 2 to 4 of this guide.

Portal-vein versus peripheral insulin, the physiology in one page

In people without T1D, pancreatic beta cells release insulin directly into the portal vein, which runs straight to the liver. The liver sees a high insulin concentration first and tells glucagon to quiet down. The remaining insulin, diluted, circulates to muscle and fat. This is portal-first insulin delivery.

In T1D, insulin is injected or pumped subcutaneously. It reaches the peripheral circulation first. The liver sees a much lower insulin concentration than it would from portal-first delivery, and glucagon is less effectively suppressed. Hepatic glucose output runs a little too warm; basal rates compensate; postprandial glucose runs higher than it would with a native release pattern. This is peripheral insulin delivery, and it is a structural feature of every current therapy, not a failure of technique.

Professor Viral Shah explored this physiology in detail in Episode 17 of the GNL Podcast. His framing of “why peripheral insulin leaves a glucagon gap, and why GLP-1 is the lever that closes it” is the clearest short explanation on record and the origin of this guide.

What adjunct therapy is, and what it is not

Adjunct therapy in T1D means:

• Alongside insulin, not instead of insulin. Basal insulin is never stopped. The adjunct reduces how much insulin is needed; it does not remove the need.
• Targeted at the physiology insulin cannot reach. Glucagon suppression, gastric emptying, appetite and satiety, energy expenditure in some settings.
• Specialist-led and individualised. Dose, titration, insulin-reduction strategy, ketone monitoring, diet and exercise adaptation, follow-up frequency. All of these need to be agreed with a diabetes care team before a single dose is taken.
• Off-label for T1D. No GLP-1RA or GLP-1/GIP agonist is licensed for T1D. Every use in T1D is off-label. The 2021 ADA/EASD consensus, the 2024 ISPAD paediatric chapter, and the 2025 Diabetes Technology Society (DTS) consensus all frame the evidence this way.

It is not:

• An insulin replacement. Claims that GLP-1RA can remove the need for insulin in T1D contradict every consensus on record and are not supported by any RCT.
• A weight-loss intervention without a clinical rationale. In T1D, the primary rationale is glycaemic and insulin-burden reduction; weight change follows as a secondary benefit in people with overweight or obesity.
• A licensed prescription. Expectations about access, insurance, and supply need to be realistic and discussed with the prescribing team.

If your diabetes care team are considering adjunct therapy with you, the conversation will cover baseline HbA1c, time in range, time below range, C-peptide status, BMI, hypoglycaemia history, exercise patterns, and the practicalities of ketone monitoring. That conversation is not something this guide replaces.

Who the evidence supports

The adult evidence base has consolidated in 2024 and 2025 and now sits at Grade B+ overall. The population in which benefit is most consistent is adults with T1D plus at least one of:

• Overweight or obesity (BMI above roughly 27).
• Clinical insulin resistance (high TDD relative to body weight, or a rising TDD trajectory).
• Postprandial hyperglycaemia not resolved by optimised meal timing and bolus strategy.
• High cardiovascular or chronic kidney disease risk.

In adults who do not fit any of those features, benefit is smaller on average and the risk-versus-gain conversation shifts. In paediatric and adolescent T1D, no Phase 3 trials exist and ISPAD 2024 is explicit that the evidence base is effectively absent; Part 4 of this guide returns to that gap honestly.

The evidence in full, with the Grade A trials and the caveats, sits in Part 2, the evidence.

Where this guide goes next

• Part 2, the evidence. The RCT spine: ADJUNCT ONE and TWO, ADJUST-T1D, Pasqua 2025 semaglutide-AID crossover, Park 2024 meta-analysis, Klein and Shah 2025 genetic-obesity substudy. What the headline numbers actually say and where the confidence intervals sit.
• Part 3, starting safely. The MDI, standard pump and AID onboarding model. Insulin reduction bands, how to split them across regimen types, ketone monitoring, and the first 12 weeks.
• Part 4, open questions. The paediatric gap, tirzepatide RCTs in flight, bone and lean-mass questions, AID algorithm adaptation, equity of access, and the live trials list.

The full FAQ lives at GLP-1 and GIP in T1D FAQ and the downloadable PDF companion is on that page.