Impact on HbA1c and body weight of switching from other GLP‐1 receptor agonists to semaglutide: A model‐based approach

Overgaard, Rune Viig; Lindberg, Søren; Thielke, Desirée

doi:10.1111/dom.13479

Cited by 22 publications

(31 citation statements)

References 34 publications

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“…In the real‐world study by Goncalves and Bell, of 40 patients switched from liraglutide to OW semaglutide, weight dropped from 110.6 ± 20 to 106 ± 27 kg ( P < .001) and body mass index from 36.4 ± 6.2 to 33.8 ± 6.2 kg/m 2 ( P < .001) 36 . The benefits of switching on weight loss are supported by a modelling study evaluating the switch from another GLP‐1RA to OW semaglutide 37 . However, additional weight loss is not consistently observed and is likely dependent on the GLP‐1RAs switched from and to.…”

Section: Benefits Of Switching From One Glp‐1ra To Anothermentioning

confidence: 88%

“…These studies, therefore, demonstrate that switching between GLP‐1RAs can provide additional benefits in terms of glycaemic control. The benefits of switching on glycaemic control are supported by a modelling study evaluating the switch from another GLP‐1RA to OW semaglutide 37 . This modelling study used data from five trials in the phase 3 OW semaglutide clinical development programme (SUSTAIN 1, SUSTAIN 2, SUSTAIN 3, SUSTAIN Japan and SUSTAIN 7) and a phase 2 dose‐finding trial to investigate the impact of switching to OW semaglutide from liraglutide, dulaglutide or exenatide ER.…”

Section: Benefits Of Switching From One Glp‐1ra To Anothermentioning

confidence: 99%

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

Jain

Amar²,

Martínez

et al. 2020

Int J Clin Pract

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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.

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Section: Benefits Of Switching From One Glp‐1ra To Anothermentioning

confidence: 88%

Section: Benefits Of Switching From One Glp‐1ra To Anothermentioning

confidence: 99%

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

Jain

Amar²,

Martínez

et al. 2020

Int J Clin Pract

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“…Various structural models were explored to describe the time course of weight change from baseline for placebo‐ and liraglutide‐treated participants. Exposure–response data over different weeks identified a deviation from a classic indirect response model previously used to describe weight loss over time . Additionally, while an indirect response model could characterize the long‐term weight changes for both the placebo and the on‐treatment groups, it consistently under‐predicted the weight changes in the treatment initiation time period .…”

Section: Methodsmentioning

confidence: 99%

“…A predefined set of covariates based on prior knowledge of the liraglutide mechanism and previous liraglutide exposure–response analyses were tested using a stepwise covariate search algorithm for all variables identified with IIV (forward inclusion: P <0.01; backwards elimination P <0.001) . The covariates assessed were: baseline body weight, baseline HbA1c, age at baseline, diabetes status (no diabetes, prediabetes or type 2 diabetes), sex (female/male), race (white, black or African American, Native Hawaiian or other Pacific Islander and American Indian or Alaska native) and trial region (Europe and Oceania, North America, Asia, Africa and South America).…”

Section: Methodsmentioning

confidence: 99%

Impact of dose‐escalation schemes and drug discontinuation on weight loss outcomes with liraglutide 3.0 mg: A model‐based approach

Papathanasiou

Strathe

Agersø

et al. 2020

Diabetes Obesity Metabolism

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Aims: To investigate the impact on weight loss of the treatment changes in overweight or obese people that may be needed in case of gastrointestinal (GI) tolerability issues during escalation of the glucagon-like peptide-1 analogue liraglutide. Materials and methods:The individual longitudinal body weight data from the main trial periods of three phase II/III trials in overweight or obese patients (56-week treatment with once-daily liraglutide 1.2, 1.8, 2.4 or 3.0 mg or placebo, n = 4952) were analysed using a non-linear mixed-effect modelling approach. Individual pharmacokinetic profiles were derived based on published pharmacokinetic models. Baseline body weight, baseline glycated haemoglobin (HbA1c), age, gender, diabetes status (no diabetes, prediabetes or type 2 diabetes), race and trial region were investigated as covariates. As a form of external validation, the model was used to predict the weight regain after treatment cessation at week 56 (data not included in model development). Results:A pharmacokinetic/pharmacodynamic model provided an adequate description of the weight loss trajectories for all studied doses. Gender and diabetes status were identified as the most influential covariates, and an underlying seasonal weight fluctuation was identified. Slower than that recommended, one-week dose-escalation algorithms led up to 2 weeks slower initial weight loss but similar long-term weight loss trajectories. Conclusions:The relationship between liraglutide systemic exposure and weight loss was successfully established in overweight or obese people. The model could predict the time course of weight regain after treatment cessation and suggests that GI tolerability can be mitigated by slower escalation with only minor impact on the weight loss trajectory. K E Y W O R D S clinical trial, dose-response relationship, GLP-1 analogue, liraglutide, pharmacodynamics

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“…In a recent model‐based approach that applied exposure‐response analysis, switching from dulaglutide, liraglutide, or exenatide extended release to semaglutide led to further reductions in body weight and HbA 1c. A slight temporary deterioration in HbA 1c was seen only with semaglutide 0.25 mg, suggesting that this dose should be avoided and that semaglutide therapy should be initiated at a higher dose …”

Section: Comparison Of Semaglutide With the Other Once‐weekly Adminismentioning

confidence: 99%

Semaglutide as a promising antiobesity drug

et al. 2019

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Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a long elimination half-life, allowing subcutaneous (sc) administration once per week. Both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recently approved once-weekly sc semaglutide for the treatment of type 2 diabetes mellitus (T2DM). The weight loss efficacy of once-weekly sc semaglutide appears to be superior compared with the other once-weekly GLP-1 RAs in patients with T2DM. Semaglutide was recently evaluated as an antiobesity drug in a phase II dose-finding trial, which demonstrated superior weight loss efficacy of once daily sc semaglutide compared with both placebo and once daily 3.0 mg liraglutide in patients with obesity but without T2DM. The magnitude of semaglutide-induced weight loss in this study exceeded the criteria of both the EMA and FDA for antiobesity drugs, and there were no safety concerns, indicating the eligibility of once daily sc semaglutide as a future antiobesity drug.

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Impact on HbA1c and body weight of switching from other GLP‐1 receptor agonists to semaglutide: A model‐based approach

Cited by 22 publications

References 34 publications

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

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

Impact of dose‐escalation schemes and drug discontinuation on weight loss outcomes with liraglutide 3.0 mg: A model‐based approach

Semaglutide as a promising antiobesity drug

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