GNL Adjunctive Therapies Guide, Part 1 of 4
Adjunctive Therapy in Type 1 Diabetes, an Overview
In clinic on a Tuesday afternoon, an adult with T1D you have known for years sits down. Their HbA1c is 7.6, their CGM data look reasonable, but their total daily insulin keeps creeping up, the weight is going the wrong way, and the post-lunch rises will not give. They ask you what else there is. This guide is what comes next in that conversation.
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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.
The first is the post-meal rise that even a well-timed bolus cannot tame; appetite cues continue to drive eating after the meal is physiologically done. The second is the slow climb in total daily insulin that creeps up year on year, basal rates feeling like they are chasing the person rather than matching them. The third is the weight gain that the insulin itself drives, anabolic by design, and the loop that follows: weight up, insulin resistance up, 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.
Portal-vein versus peripheral insulin
In people without T1D, beta cells release insulin straight into the portal vein, which runs 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. That is portal-first delivery.
In T1D, insulin is injected or pumped subcutaneously and reaches the peripheral circulation first. The liver sees a much lower insulin concentration than it would from a portal-first signal, and glucagon is less effectively suppressed. Hepatic glucose output runs a little too warm; basal rates compensate; post-meal glucose runs higher than a native release pattern would produce. This is a structural feature of every current therapy, not a failure of technique.
GLP-1RA and GLP-1/GIP agonists work partly by suppressing glucagon directly at the alpha cell, slowing gastric emptying, and reducing appetite. They do not replace the portal-first signal, but they reach parts of the physiology that peripheral insulin cannot. Professor Viral Shah explored this in detail in Episode 17 of the GNL Podcast; that conversation was the inspiration for this guide.
The lever, plainly stated. Adjunctive therapy in T1D is not insulin replacement; it is the lever that closes the glucagon, gastric-emptying and appetite gap that peripheral insulin cannot reach.
What adjunct therapy is, and what it is not
Adjunct therapy in T1D means: alongside insulin, never instead of it; targeted at the physiology insulin cannot reach (glucagon, gastric emptying, appetite, energy balance); specialist-led and individualised; and off-label. No GLP-1RA or GLP-1/GIP agonist is licensed for T1D, and the 2021 ADA/EASD consensus, the 2024 ISPAD paediatric chapter and the 2025 Diabetes Technology Society consensus all frame it that way.
It is not an insulin replacement; claims that GLP-1RA can remove the need for insulin in T1D contradict every consensus on record. It is not a weight-loss intervention without a clinical rationale; in T1D the primary rationale is glycaemic and insulin-burden reduction, with weight change a secondary benefit in people with overweight or obesity. And it is not a routine prescription; access, insurance and supply realities need an honest conversation with the prescribing team.
If your diabetes care team is 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 consolidated through 2024 and 2025 and now sits at Grade B+ overall, with Grade A pivotal RCTs anchoring the headline claims and Grade C consensus and observational work weighted in for practice translation. Benefit is most consistent in 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); post-meal hyperglycaemia not resolved by optimised meal timing and bolus strategy; or high cardiovascular or chronic kidney disease risk.
Outside those features, average benefit is smaller 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 returns to that gap honestly.
The full evidence walk, with the Grade A trials and the caveats, is in Part 2. The April 2026 update for this guide is being sent to Professor Shah for fresh review.
Important note
This content is for educational exploration only. It describes average responses and general principles drawn from clinical trial and consensus evidence. It is not medical advice and cannot replace individual clinical guidance from your diabetes care team. GLP-1 and GLP-1/GIP therapies remain off-label for type 1 diabetes; any decision to start, adjust or stop them should be made jointly with a specialist diabetes team. With thanks to Professor Viral N Shah, Professor David Klonoff and the DTS panel, the ADJUNCT trial teams, the McGill semaglutide-AID team, and the ISPAD 2024 chapter authors, whose work defines the modern evidence base.
Part 1 of 4
Adjunctive Therapy in T1D, an Overview