• What is the available evidence about the switch between dulaglutide and other GLP-RAs in general?
• What is the available evidence about the switch between dulaglutide and semaglutide?
• What is the available evidence about the switch between dulaglutide and liraglutide?
• How to select the new GLP-1 RA, and what are some general considerations?
• Is a washout needed and what should be the initial dose of the new GLP-1 RA?
  • When should the new GLP-1 RA be administered?
  • Dosing and posology of new GLP-1 RA
• Will the patient tolerate and respond to the new GLP-1 RA?
• What advice and information will the patient need?
• What is relevant when switching from or to dulaglutide?
• Treatment decision

Eli Lilly and Company has not sponsored any studies on the effects of switching between dulaglutide and other glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Therefore, we cannot provide any specific recommendations.

To identify possible published evidence and recommendations on how to switch between GLP-1 RAs in general, a literature search was completed on the 21st of November 2022 in the biomedical database Ovid Embase®. We searched for publications related to glucagon-like peptide-1 receptor agonists mentioning “GLP-1 RAs” and “switch” in the title. The search found 44 publications, that were manually screened to remove publications not related to a switch between GLP-1 RAs. A total of 10 publications met our criteria.

Database: Embase <1974 to 2022 November 21>

1. (glucagon* or GLP*).m_titl. (24803)
2. "switch*".m_titl. (51828)
3. exp glucagon like peptide 1 receptor agonist/ (43352)
4. 1 and 2 and 3 (44)
5. from 4 keep 2,4-6,9,14-15,19-20,42 (10)

The 10 results included 2 practical guidelines for switching between GLP-1 RAs1,2 and 1 study aimed to study the efficacy and tolerability of once-weekly GLP-1 RAs.3

Eli Lilly and Company has not sponsored any studies on the effects of switching between dulaglutide and semaglutide.4

To identify possible published evidence and recommendations on how to switch between dulaglutide and semaglutide, a literature search was completed on the 16th of August 2023 in the biomedical database Ovid Embase®. We searched for publications related to dulaglutide and semaglutide mentioning “switch” in the title. The search found 6 publications, that were manually screened to remove publications not related to a switch between dulaglutide and semaglutide. A total of 5 publications met our criteria.

Database: Embase <1974 to 2023 August 15>

1. dulaglutide.m_titl. (723)
2. semaglutide.m_titl. (1323)
3. "switch*".m_titl. (54648)
4. 1 and 2 and 3 (6)
5. from 4 keep 2-6 (5)

The 5 results included 3 publications focusing on the switch from dulaglutide to semaglutide5-7, and 1 focusing on the switch from semaglutide to dulaglutide8. These studies are briefly summarised below with a focus on the switching between the products. For further information on the results of the studies, please consult the individual publications. 

Two of the publications were multicentre, open-labelled, prospective, randomized, parallel-group comparison studies.

• They aimed to compare the effects of once-weekly subcutaneous semaglutide against liraglutide 0.9–1.8 mg/day or dulaglutide 0.75 mg/weekly on glycemic control in 100 Japanese patients with T2D.
• Patients treated with liraglutide or dulaglutide were either switched to semaglutide or continued current therapy.
• The primary endpoint was the mean change in glycated haemoglobin over 24 weeks.
• Participants in the semaglutide group followed a semaglutide dose-escalation regimen (0.25 mg semaglutide was administered once weekly for 4 weeks and then the maintenance dose of 0.5–1.0 mg was administered).5,6

The other publication focusing on the switch from dulaglutide to semaglutide was a retrospective real-world effectiveness analysis. 

• The study included 164 adults with T2D who prior to switching to semaglutide , were on a stable dose of liraglutide or dulaglutide.
• A change in HbA1c was the primary outcome. 
• Of the 25 patients on dulaglutide once-weekly at the time of the switch, 2 (8%) and 23 (92%) patients were on dulaglutide doses of 0.75 and 1.5 mg/week, respectively.
• The median doses of dulaglutide once-weekly prior to switching were 1.5 mg/week.
• At the time of the switch, patients were started on the following semaglutide once-weekly doses: 
  • 48 (29.3%) 0.25 mg/week 
  • 106 (64.6%) on 0.5 mg/week and
  • 10 (6.1%) on 1.0 mg/week.
• The final recorded dose of semaglutide on study completion for the 147 patients, who had continued on the medication was:
  • 0.25 mg/week for 1 patient (0.6%),
  • 0.50 mg/week for 32 patients (21.8%), and
  • 1.0 mg/week for 114 patients (77.6%).
• The median final dose of semaglutide once-weekly was 1.0 mg/week.7
  

The last publication focuses on the switch from semaglutide to dulaglutide, and evaluated HbA1c and body weight changes when semaglutide 0.5- or 1.0-mg once-weekly is switched to dulaglutide 3.0- or 4.5-mg once-weekly via exposure-response modelling.8

Eli Lilly and Company has not sponsored any studies on the effects of switching between dulaglutide and liraglutide.4

To identify possible published evidence and recommendations on how to switch between dulaglutide and liraglutide, a literature search was completed on the 17th of August 2023 in the biomedical database Ovid Embase®. We searched for publications related to dulaglutide and liraglutide mentioning “switch” in the title. The search found 5 publications, that were manually screened to remove publications not related to a switch between dulaglutide and liraglutide. A total of 2 publications met our criteria. 

Database: Embase <1974 to 2023 August 16>

1. dulaglutide.m_titl. (723)
2. liraglutide.m_titl. (3776)
3. "switch*".m_titl. (54656)
4. 1 and 2 and 3 (5)
   
5. from 4 keep 1,5 (2)

These 2 studies are briefly summarised below with a focus on the switching between the products.9,10For further information on the results of the studies, please consult the individual publications. 

The first publication discusses an open-label, prospective, randomized, parallel-group controlled trial

• 30 Japanese patients with type 2 diabetes treated with once-daily liraglutide (0.6 or 0.9 mg) were randomly switched to
  • liraglutide (0.5 mg once-weekly) or
  • dulaglutide (0.75 mg once weekly) group.
• Post-treatment, changes in the HbA1c level from baseline to weeks 8, 16, and 26 were evaluated.9

The second publication focuses on a 12-week, multicenter, open-label, prospective, randomized, parallel-group comparison trial.

• The study included 31 Japanese patients with type 2 diabetes, who were being administered liraglutide once-daily for >3 months.
• The patients were randomly assigned to either switch to dulaglutide 0.75 mg once weekly or continue taking 0.9 mg liraglutide once daily.
• Changes in the Diabetes Treatment Satisfaction Questionnaire score from baseline to week 12 was the primary outcome.10

Physicians should follow their clinical judgment, taking into account the patient’s glycaemic response and needs when deciding how to transition from one GLP-1 RA to another.4 

Aspects that might need further consideration, apart from glycaemic control, cardiovascular prevention, or aspects of weight management, include but are not limited to:1,2

• comorbidities to address any contraindications or warnings1,2 
• concomitant medication including
  • those with narrow therapeutic windows1, or
  • sulfonylurea or insulin dose reduction to reduce the risk of hypoglycaemia.2

Available practice advice for switching between GLP-1 RAs is mainly based on clinical experience.1,2

The available evidence from systematic studies is limited:

The perspectives from 10 healthcare professionals experienced with switching patients with T2D were collated, focussing on switching to once weekly semaglutide. It has been concluded that switching can provide clinical benefits. However, switching should be individualized, explaining to patients the temporary character of possible gastrointestinal events. Furthermore, a transient deterioration of glycaemic control is possible until full effect of the new GLP-1 RA’s final maintenance dose is achieved.2

A monocentric, retrospective, real-world cohort study confirmed the effectiveness and tolerability of the once-weekly GLP-1 RA in a routine clinical practice. Furthermore, switching to another once-weekly GLP-1 RA might help patients not responding to a previous GLP-1RA to achieve metabolic targets.3

Here some aspects important to discuss with the patient:

• Any concern the patient might have and why the switch is necessary.2
• How to use the new device, if applicable.1
• Changes to the dosing regimen and how often to administer the new GLP-1 RA.1
• The possibility of a transient loss of glycaemic control during dose titration and time to steady state.2
• The possibility of gastrointestinal adverse events that are usually transient and can be mitigated by smaller meal size and lower meal fat content.2

For patients switching to Trulicity in combination with other antidiabetics, the recommended dose is 1.5 mg once weekly.11

In vulnerable populations, a starting dose of 0.75 mg once weekly can be considered.11

For additional glycaemic control,11

• the 1.5 mg dose may be increased after at least 4 weeks to 3 mg once weekly.
• the 3 mg dose may be increased after at least 4 weeks to 4.5 mg once weekly.

The maximum dose is 4.5 mg once weekly.11

When dulaglutide is added to existing therapy of a sulphonylurea or insulin, a reduction in the dose of sulphonylurea or insulin may be considered to reduce the risk of hypoglycaemia.11

Pharmacokinetic properties of dulaglutide summarizes the relevant pharmacokinetic properties of dulaglutide. See SmPC for full prescribing information.

When transitioning a patient from one GLP-1 RA to another, the prescribing information of the applicable GLP-1 RAs and pharmacokinetic/pharmacodynamic profiles should be considered. For full prescribing information please refer to the Summary of Product Characteristics (SmPC) of both GLP-1 RAs.4