Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial

Frías, Juan P.; Deenadayalan, Srikanth; Erichsen, Lars; Knop, Filip K.; Lingvay, Ildiko; Macura, Stanislava; Mathieu, Chantal; Pedersen, Sue D.; Davies, Melanie J.

doi:10.1016/s0140-6736(23)01163-7

Cited by 82 publications

(36 citation statements)

References 26 publications

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“…The latter study included pharmacokinetics and showed half-life of 159-195 h, with a median tmax of 24-72 h which would be consistent with weekly administration of the amylin agonist (Enebo et al, 2021). A more recent phase 2 study has also confirmed the efficacy of combination cagrilintide with semaglutide leading to 15.6% weight reduction at 32 weeks relative to baseline, and with greater weight loss than each component alone (Frias et al, 2023).…”

Section: Actions Of Incretin Receptor Agonists On Liver Diseasementioning

confidence: 76%

Newer pharmacological interventions directed at gut hormones for obesity

Camilleri,

Acosta

2023

British J Pharmacology

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The objective is to review the newer pharmacological interventions for obesity, specifically single, dual, and triple incretin receptor agonists that are either available or in the pipeline for treatment of obesity. The three incretin receptor targets are glucagon like peptide‐1 (GLP‐1), glucose‐dependent insulinotropic peptide (GIP), and glucagon. There are several approved single or dual incretin agonists which are administered subcutaneously daily (e.g., liraglutide) or weekly (e.g., semaglutide, dulaglutide, and exenatide QW), and experimental dual or triple incretin agonists. Other analogs of amylin, peptide YY, and oxyntomodulin, as well as a combination GLP1R agonist and GIPR antagonist are also being developed. Oral semaglutide (administered daily) is approved for type 2 diabetes and is on track for regulatory review for obesity. The review includes specifically perspectives on the effects of these mechanisms and pharmacological agents on gastric emptying which contribute to satiation and weight loss, in addition to the established evidence on effects on central mechanisms controlling appetite. In the future, it is anticipated that small molecule GLP‐1 receptor agonists (e.g., oral danuglipron) will be developed. These pharmacological agents are having significant impact on glycemic control and obesity and their co‐morbidities.

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Section: Actions Of Incretin Receptor Agonists On Liver Diseasementioning

confidence: 76%

Newer pharmacological interventions directed at gut hormones for obesity

Camilleri,

Acosta

2023

British J Pharmacology

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“…In a more recent study in subjects with type 2 diabetes, this combination produced a 15.6% weight loss at 32 weeks. This study also had no placebo group 175…”

Section: Emerging Treatmentsmentioning

confidence: 99%

Effectiveness and safety of drugs for obesity

Henderson Lewis,

Sloan,

Bessesen

et al. 2024

BMJ

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Recent publicity around the use of new antiobesity medications (AOMs) has focused the attention of patients and healthcare providers on the role of pharmacotherapy in the treatment of obesity. Newer drug treatments have shown greater efficacy and safety compared with older drug treatments, yet access to these drug treatments is limited by providers’ discomfort in prescribing, bias, and stigma around obesity, as well as by the lack of insurance coverage. Now more than ever, healthcare providers must be able to discuss the risks and benefits of the full range of antiobesity medications available to patients, and to incorporate both guideline based advice and emerging real world clinical evidence into daily clinical practice. The tremendous variability in response to antiobesity medications means that clinicians need to use a flexible approach that takes advantage of specific features of the antiobesity medication selected to provide the best option for individual patients. Future research is needed on how best to use available drug treatments in real world practice settings, the potential role of combination therapies, and the cost effectiveness of antiobesity medications. Several new drug treatments are being evaluated in ongoing clinical trials, suggesting that the future for pharmacotherapy of obesity is bright.

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“…Amongst the subcutaneous agents, three molecules stand out. CagriSema (combining the GLP1RA semaglutide with the long-acting amylin analogue cagrilintide) achieved a WL of −15.6% in PWT2D [ 82 ]. Cotatutide (a dual GLP1 and GCGRA), showed a 46% reduction in ACR and a WL of 7.3% in a phase 2b study in PWT2D and CKD with ACR ≥50 mg/g [ 83 ].…”

Section: Limitations Uncertainties and Future Directionsmentioning

confidence: 99%

Are we ready for an adipocentric approach in people living with type 2 diabetes and chronic kidney disease?

Moreno-Pérez,

Reyes-García,

Modrego-Pardo

et al. 2024

Clinical Kidney Journal

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We are entering a new era in the management of adiposity-based chronic disease (ABCD) with type 2 diabetes (T2D) and related chronic kidney disease (CKD). ABCD, T2D and CKD can affect almost every major organ system and have a particularly strong impact on the incidence of cardiovascular disease (CVD) and heart failure. ABCD and the associated insulin resistance are at the root of many cardiovascular, renal and metabolic (CKM) disorders, thus an integrated therapeutic framework using weight loss (WL) as a disease-modifying intervention could simplify the therapeutic approach at different stages across the lifespan. The breakthrough of highly effective WL drugs makes achieving a WL of >10% possible, which is required for a potential T2D disease remission as well as for prevention of microvascular disease, CKD, CVD events and overall mortality. The aim of this review is to discuss the link between adiposity and CKM conditions as well as placing weight management at the centre of the holistic CKM syndrome approach with a focus on CKD. We propose the clinical translation of the available evidence into a transformative Dysfunctional Adipose Tissue Approach (DATA) for people living with ABCD, T2D and CKD. This model is based on the interplay of four essential elements (i.e. adipocentric approach and target organ protection, dysfunctional adiposity, glucose homeostasis, and lifestyle intervention and de-prescription) together with a multidisciplinary person-centred care. DATA could facilitate decision-making for all clinicians involved in the management of these individuals, and if we do this in a multidisciplinary way, we are prepared to meet the adipocentric challenge.

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Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial

Cited by 82 publications

References 26 publications

Newer pharmacological interventions directed at gut hormones for obesity

Newer pharmacological interventions directed at gut hormones for obesity

Effectiveness and safety of drugs for obesity

Are we ready for an adipocentric approach in people living with type 2 diabetes and chronic kidney disease?

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