Switching between GLP‐1 receptor agonists in clinical practice: Expert consensus and practical guidance

Abstract

Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are an established treatment for patients with type 2 diabetes (T2D). Differences between GLP‐1RAs in pharmacokinetics, dosing regimens and clinical effects, including cardiovascular (CV) outcomes, mean there may be benefits to switching from one to another. However, clinical guidance on switching is lacking and data from clinical trials are limited. This article provides a clinical perspective and consensus on the benefits of switching between GLP‐1RAs, the triggers for switching and how best to manage this in clinical practice. Once weekly (OW) semaglutide is used as an example to illustrate how the authors might switch to a different GLP‐1RA in clinical practice. Methods Literature was searched and perspectives from 10 healthcare professionals with experience in switching patients with T2D to OW semaglutide from another GLP‐1RA were collated. Results Medical triggers for switching to another GLP‐1RA included HbA1c targets not being met, a desire for additional weight loss, poor adherence, patients moving to increased CV risk status and adverse effects with the current GLP‐1RA. Non‐medical triggers for switching included patient preference, cost, formulary changes and insurance mandates. Once the decision to switch is made, an individualised approach is recommended, based on considerations that include reimbursement requirements, treatment duration with (and dose of) previous GLP‐1RA, the patient's experience initiating the prior GLP‐1RA, any concomitant treatment and clinical characteristics. When switching, it is important to emphasise that treatment burden will not increase and that if gastrointestinal adverse effects occur, they are typically transient. Any transient gastrointestinal adverse effects that may occur (or recur) when switching to another GLP‐1RA can be reduced by slow up‐titration and advising patients to reduce food portion sizes and fat intake. Conclusion Switching from one GLP‐1RA to another, such as OW semaglutide, can provide clinical benefits and may delay the need for treatment intensification.

Switch-to-Semaglutide Study (STS-Study): a Retrospective Cohort Study

“…To date, only limited data exist for switching GLP-1 analogue therapy to semaglutide-containing treatment even though practical and expert consensus recommendations based on empirical and parallel or case-control data were recently published [1,2]. To the best of our knowledge, only a letter to the editor analysing a switch from liraglutide to semaglutide has been published so far [12].…”

“…Despite recent expert recommendations robust clinical data on treatment switches of glucagon-like peptide 1 (GLP-1) receptor agonists is scarce [1,2]. GLP-1 agonists are an important cornerstone for the treatment of type 2 diabetes [3] and have been proven to be highly efficacious not only for glucose control but also for weight loss [4,5].…”

“…Additionally, the model provides an estimate of corresponding GLP-1 levels for liraglutide, dulaglutide and exenatide in comparison to semaglutide dosing for a treatment switch which would allow an equipotential dosing switch. However, whether these theoretical estimations hold true in clinical practice and whether gastrointestinal tolerability or other side effects are comparable when patients are switched from a pre-existing GLP-1 analogue therapy to semaglutide are unclear [1,2].…”

Understanding the place for GLP‐1RA therapy: Translating guidelines for treatment of type 2 diabetes into everyday clinical practice and patient selection

“…When initiating GLP‐1RAs, it is important to explain effects and potential side effects to highlight what to expect for patients. If GLP‐1RA therapy has been initiated, switching between GLP‐1RA compounds may be considered an alternative to intensifying treatment with another antidiabetic drug to provide additional clinical benefits 52 (eg, switching from a short‐acting‐ to long‐acting GLP‐1RA). Patients should then start over with up‐titrating to limit GI‐side effects.…”

Efficacy of Semaglutide in a Subcutaneous and an Oral Formulation

“…However, both subcutaneous and oral semaglutide have been reported to be more costeffective and offer lower cost-of-control compared with other injectable GLP-1RAs and oral glucose-lowering drugs, although this may vary between different patient cohorts and healthcare settings (58)(59)(60)(61)(62)(63)(64). In addition, switching may be dependent on non-medical decisions outwith the physician's choice, with a recent expert consensus indicating that non-medical triggers for switching to subcutaneous semaglutide from other GLP-1RAs also included formulary changes and insurance mandates, as well as cost considerations (65).…”