Gastrointestinal effects of GLP-1 receptor agonists: mechanisms, management, and future directions

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2024, Volume and Issue: 9(10), P. 957 - 964

Published: Aug. 1, 2024

Language: Английский

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A Hypothesis That Glucagon-like Peptide-1 Receptor Agonists Exert Immediate and Multifaceted Effects by Activating Adenosine Monophosphate-Activate Protein Kinase (AMPK)

Life, Journal Year: 2025, Volume and Issue: 15(2), P. 253 - 253

Published: Feb. 7, 2025

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce bodyweight and blood glucose. Extensive evidence from randomized controlled trials has indicated that GLP-1RAs have benefits well beyond weight loss glucose control, extending reductions in cardiovascular mortality to prostate cancer risk. Notably, some of for the cardiovascular–kidney–metabolic (CKM) system arise before occurs reasons are not entirely clear but key patient care drug development. Here, we hypothesize act by inducing calorie restriction activating adenosine monophosphate-activated protein kinase (AMPK), which only provides an explanation unique effectiveness also indicates a common mechanism shared effective CKM therapies, including salicylates, metformin, statins, healthy diet, physical activity. Whether AMPK activation is obligatory therapies should be considered. As such, propose action explain how it overarching framework identifying means preventing treating cardiovascular, kidney, metabolic related diseases, as informing complementary question components lifestyle.

Language: Английский

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Recent advances in peptide-based therapies for obesity and type 2 diabetes

Peptides, Journal Year: 2024, Volume and Issue: 173, P. 171149 - 171149

Published: Jan. 5, 2024

Options for the treatment of type 2 diabetes mellitus (T2DM) and obesity have recently been expanded by results several large clinical trials with incretin-based peptide therapies. Most these studies conducted glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, which is available as a once weekly subcutaneous injection daily tablet, injected dual tirzepatide, interacts receptors GLP-1 glucose-dependent insulinotropic polypeptide (GIP). In individuals T2DM therapies achieved reductions glycated haemoglobin (HbA1c) > 2% lowered body weight 10%. some studies, agents tested in non-diabetic, obese at much higher doses 15%. Emerging evidence suggests can also offer cardio-protective potentially reno-protective effects. Other early development, notably triple GLP-1/GIP/glucagon (retatrutide) combination semaglutide amylin analogue cagrilintide (CagriSema), shown strong efficacy. Although incretin incur adverse gastrointestinal effects are most patients mild-to-moderate transient but result cessation cases. Thus, efficacy new enhancing opportunity to control blood glucose improve obesity.

Language: Английский

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Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities

Peptides, Journal Year: 2025, Volume and Issue: 187, P. 171380 - 171380

Published: March 11, 2025

Recent studies with peptide-based incretin herapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and dual tirzepatide that engages receptors for GLP-1 glucose-dependent insulinotropic polypeptide (GIP). Randomised clinical trials 'real-world' confirmed marked glucose-lowering weight-lowering efficacy of these agents across diverse populations. These include different ethnic groups, young elderly individuals without diabetes and/or overweight or obesity. also protections against development progression cardiovascular renal diseases are additive to benefits conferred by improved control blood glucose body weight. Emerging evidence suggests therapies could additionally ameliorate fatty liver disease, chronic inflammation, sleep apnea possibly degenerative bone disorders cognitive decline. New incretin-based peptide in a long-acting glucagon (LY3324954), GLP-1/glucagon agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon (retatrutide, efocipegtrutide), combination amylin analogue cagrilintide (CagriSema), unimolecular GLP-1/amylin (amycretin), GIP antibody agonism (MariTide). The creation multi-targeting synthetic peptides provides opportunities management type 2 obesity as well new therapeutic approaches an expanding list associated co-morbidities. aim review is acquaint reader developments field from 2023 present (February 2025).

Language: Английский

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Clinical efficacy and cost‐effectiveness of metformin in different patient populations: A narrative review of real‐world evidence

Diabetes Obesity and Metabolism, Journal Year: 2024, Volume and Issue: 26(S3), P. 20 - 30

Published: June 28, 2024

Over the past two decades, diabetes pharmacopoeia has flourished, with new drugs that, on top of their glucose-lowering efficacy, have been shown to protect heart and kidney. Despite these opportunities, metformin retains a pivotal role among agents. As one few available insulin sensitizers, is an effective, safe, overall well-tolerated drug backed by over 60 years clinical experience, including evidence for potential benefits beyond glucose reduction across different ages, sexes, genetic backgrounds, geographical areas, stages disease. Although there some discussion whether offers most effective front-line option in newly diagnosed type 2 (T2D), it remains natural companion all other Furthermore, comes at very low cost and, as such, extremely high cost-effectiveness, particularly given serious economic burden associated complications. This financial advantage relevant resource-constrained healthcare systems, where affordability may be instrumental implementing treatment evergrowing number individuals. We present here compelling real-world support efficacy cost-effectiveness patient populations, highlighting areas more population-based studies are needed further incorporate consolidate its use pharmacological management T2D.

Language: Английский

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Aspiration risk and strategic approach for patients receiving GLP-1 receptor agonists undergoing elective surgery

Current Medical Research and Opinion, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 21

Published: April 16, 2025

Perioperative management of patients receiving a glucagon-like peptide-1 receptor agonist (GLP-1 RA) remains challenging for the anesthesiologist. Despite approval GLP-1 RAs 2 decades ago, recent reports aspiration and postoperative pulmonary complications drew attention to this group medications resulted in multiple societal guidelines that would provide recommendations anesthesiologists proceduralists on appropriate perioperative RAs. However, despite these proposed options, there was lack adequate evidence support holding versus continuing medication, as well data related role gastric ultrasound decision-making process. The release studies evaluating impact outcomes more controversy uncertainty clinician anesthesiologist follow. ultimate goal is evaluate an individual patient's risk aspiration, rather than assuming low when medication appropriately or high if not it. Furthermore, it unclear whether types medicines unnecessary postponing surgery may result adverse outcomes. In narrative review, we present summary existing literature topic with focus recommendation include utilization based their risks.

Language: Английский

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Long‐term delirium and survival outcomes in patients treated with GLP‐1 receptor agonists versus metformin in type 2 diabetes: A population‐based cohort study

Diabetes Obesity and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Abstract Aim Type 2 diabetes mellitus (T2DM) is associated with an increased risk of delirium and mortality. While glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) provide metabolic neuroprotective benefits, their long‐term impact on remains uncertain. This study compares GLP‐1 RAs metformin in relation to mortality T2DM patients using real‐world data. Methods A retrospective cohort was conducted the TriNetX global federated research network, which primarily comprises U.S.‐based healthcare organisations (approximately 85%), additional sites Europe, Asia‐Pacific Middle East. Adults (≥18 years) who initiated or were included. Propensity score matching (PSM) balances baseline characteristics. The primary outcome incident delirium; secondary all‐cause Kaplan–Meier survival curves time‐dependent Cox models assessed associations. Results After 1:1 PSM ( N = 63 096 per group), showed no overall reduction (AHR: 0.98, 95% CI: 0.94–1.02, p 0.3628). However, they protective first 5 years 0.89, 0.86–0.92, < 0.0001) but between 10 1.15, 1.04–1.26, 0.0046). Subgroup analysis revealed lower middle‐aged (40–79 those HbA1c <7.5%. Higher observed Asian Native Hawaiian/Pacific Islander populations. these findings should be interpreted caution due relatively small subgroup sizes limited representativeness groups within predominantly database, together accounted for less than 5% cohort. Mortality absolute terms (6.28% vs. 9.95%) higher hazard 1.16, 1.12–1.21, 0.001). Conclusions RA use initially a delirium, this association reversed over time. variations suggest individualised treatment considerations. Metformin preferred option given its stable cognitive benefits.

Language: Английский

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Current management of chronic kidney disease in type‐2 diabetes—A tiered approach: An overview of the joint Association of British Clinical Diabetologists and UK Kidney association (ABCD‐UKKA) guidelines

Diabetic Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 17, 2024

Abstract A growing and significant number of people with diabetes develop chronic kidney disease (CKD). Diabetes‐related CKD is a leading cause end‐stage (ESKD) have high morbidity mortality, predominantly related to cardiovascular (CVD). Despite advances in care over the recent decades, most type 2 are likely die CVD before developing ESKD. Hyperglycaemia hypertension modifiable risk factors prevent onset progression CVD. People often dyslipidaemia per se an independent factor for CVD, therefore require intensive lipid lowering reduce burden Recent clinical trials demonstrated reduction composite end point events (significant decline function, need replacement therapy death) sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors, non‐steroidal mineralocorticoid receptor antagonist finerenone glucagon‐like peptide 1 agonists. The Association British Clinical Diabetologists (ABCD) UK Kidney (UKKA) Diabetic Disease Speciality Group previously undertaken narrative review critical appraisal available evidence inform practice guidelines management hyperglycaemia, hyperlipidaemia adults CKD. This 2024 abbreviated updated guidance summarises recommendations implications healthcare professionals who treat primary, community secondary settings.

Language: Английский

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Special Issue: “Anti-inflammatory Effects of Glucagon-like Peptide-1”

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 1997 - 1997

Published: Feb. 7, 2024

From the failure of gut extracts in diabetic patients’ therapy to effective action cardiovascular outcomes [...]

Language: Английский

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Cardiovascular outcomes with exenatide in type 2 diabetes according to ejection fraction: The EXSCEL trial

European Journal of Heart Failure, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 9, 2024

Language: Английский

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