Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity

Diabetes Care, Journal Year: 2024, Volume and Issue: unknown

Published: June 6, 2024

The development of glucagon-like peptide 1 receptor agonists (GLP-1RA) for type 2 diabetes and obesity was followed by data establishing the cardiorenal benefits GLP-1RA in select patient populations. In ongoing trials investigators are interrogating efficacy these agents new indications, including metabolic liver disease, peripheral artery Parkinson Alzheimer disease. success GLP-1–based medicines has spurred molecular entities combinations with unique pharmacokinetic pharmacodynamic profiles, exemplified tirzepatide, a GIP-GLP-1 coagonist. Simultaneously, investigational molecules such as maritide block GIP activate GLP-1 receptor, whereas retatrutide survodutide enable simultaneous activation glucagon receptors. Here I highlight evidence medicines, while discussing that inform safety, focusing on muscle strength, bone density fractures, exercise capacity, gastrointestinal motility, retained gastric contents anesthesia, pancreatic biliary tract disorders, risk cancer. Rapid progress highly efficacious anticipated differentiation newer subsets will provide greater opportunities use personalized medicine approaches to improve health people living cardiometabolic disorders.

Language: Английский

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Targeting the incretin system in obesity and type 2 diabetes mellitus

Nature Reviews Endocrinology, Journal Year: 2024, Volume and Issue: 20(8), P. 447 - 459

Published: April 17, 2024

Language: Английский

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Use of GLP1 receptor agonists in early pregnancy and reproductive safety: a multicentre, observational, prospective cohort study based on the databases of six Teratology Information Services

BMJ Open, Journal Year: 2024, Volume and Issue: 14(4), P. e083550 - e083550

Published: April 1, 2024

Objectives Glucagon-like peptide 1 receptor agonists (GLP1-RA) are indicated for the treatment of type 2 diabetes and more recently weight loss. The aim this study was to assess risks associated with GLP1-RA exposure during early pregnancy. Design This multicentre, observational prospective cohort compared pregnancy outcomes in women exposed either or obesity those two reference groups: (1) at least one non-GLP1-RA antidiabetic drug first trimester (2) a group overweight/obese without diabetes, between 2009 2022. Setting Data were collected from databases six Teratology Information Services. Participants included 168 pregnancies trimester, alongside 156 163 women. Results Exposure not risk major birth defects when (2.6% vs 2.3%; adjusted OR, 0.98 (95% CI, 0.16 5.82)) 3.9%; OR 0.54 (0.11 2.75)). For group, cumulative incidence live births, losses terminations 59%, 23% 18%, respectively. In corresponding estimates 69%, 26% 6%, while they 63%, 29% 8%, Cox proportional cause-specific hazard models no increased versus groups, both crude analyses. Conclusions offers reassurance cases inadvertent Due limited sample size, larger studies required validate these findings.

Language: Английский

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Glucagon-like peptide-1 receptor agonist use in pregnancy: a review

American Journal of Obstetrics and Gynecology, Journal Year: 2024, Volume and Issue: 232(1), P. 17 - 25

Published: Aug. 23, 2024

Language: Английский

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Medical therapy to treat obesity and optimize fertility in women of reproductive age: a narrative review

Reproductive Biology and Endocrinology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 6, 2025

Overweight and obesity—chronic illnesses in which an increase body fat promotes adipose tissue dysfunction abnormal mass resulting adverse metabolic, biomechanical, psychosocial health consequences—negatively impact female fertility. Adverse conception outcomes are multifactorial, ranging from poor oocyte quality implantation issues to miscarriages fetal issues. However, with the advent of novel pharmacologic agents, significant weight loss can be achieved, improving chances healthy pregnancies, their use should considered during periconceptual counseling. There currently 6 FDA-approved medications for loss: 2 GLP1-receptor agonists (GLP1-RAs) liraglutide semaglutide, 1 dual GLP-1 gastric inhibitory peptide agonist (GLP1-GIP) tirzepatide, Contrave (naltrexone/bupropion), Qsymia (phentermine/Topamax), Xenical (orlistat). GLP1-RAs reduce food cravings, appetite, "food noise" improve insulin sensitivity satiety, all lead loss, 30% starting total or greater, depending on specific agent used. Their efficacy relative safety make them first-line options women seeking lose year before trying conceive. Contrave, combination naltrexone bupropion, seems work most significantly by inhibiting rewarding reinforcing effects consumption. Clinical trials report ~ 6% as well improvement metabolic factors. It may also a woman's ability conceive mitigating PCOS endometriosis reducing drive alcohol smoking. Qsymia, phentermine topiramate, results more than but cannot used acute preconception period, its topiramate component is known teratogen. Orlistat another medication loss; however, it much less often other anti-obesity drugs because relatively lower side effects. Bariatric surgery, (25–50%), was previously regarded durable method GLP1-RAs. Given inherent risks development vitamin (i.e. B12, folate, D) mineral iron, copper, zinc) deficiencies, that mother fetus, recommended delay 1–2 years prior attempting pregnancy, bariatric surgery not therapy obesity management reproductive age, especially who hoping quickly nearing advanced maternal age. Clinically meaningful achievable pharmacotherapy help enhance fertility age overweight obese. Current research supports enhancing spontaneous response ovulation induction. Further upon live birth rates warranted. For long they stopped at least months conception. well, though loss. Phentermine teratogenic contraception get pregnant.

Language: Английский

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Considering the use of GLP-1 receptor agonists in women with obesity prior to pregnancy: a narrative review

Archives of Gynecology and Obstetrics, Journal Year: 2025, Volume and Issue: 311(5), P. 1241 - 1247

Published: Jan. 7, 2025

Abstract Purpose Metabolic disease, including obesity and type 2 diabetes, are amongst the most significant health issues facing women of reproductive age. To date, no antenatal weight management tools have reduced risk adverse outcomes for with their offspring, resulting in a shift focus to pre-conception period. Although not yet recognised international guidelines, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) being increasingly used prior conception. Methods A literature search PubMed, Medline, Embase databases identified relevant articles describing use GLP-1 RAs during pregnancy. Papers were selected based on relevance originality, clinical trials, large observational studies meta-analyses preferentially included. Results This narrative review summarises mechanism action effects observed non-pregnant adults. It synthesises available data from human animal regarding safety efficacy pregnancy, consequences inadvertent drug exposure early In considering need balance risks metabolic disease posed by exposure, it highlights areas where further research is needed guide decision-making. Conclusion may role facilitating loss improving However, there currently insufficient evidence demonstrate that this class drugs pregnancy improves outcomes.

Language: Английский

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The Potential Role of Glucagon-Like Peptide-1 (GLP-1) Agonists for Polycystic Ovary Syndrome

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 26, 2025

Polycystic ovary syndrome (PCOS) poses a multifaceted challenge, affecting women through genetic susceptibility, obesity, and insulin resistance. This narrative review explores the potential therapeutic role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in PCOS treatment, with focus on weight loss associated metabolic changes. The off-label use GLP-1 RAs this population helps to treat comorbid obesity. By thoroughly examining diagnostic criteria, current treatments, clinical trial outcomes involving RAs, research reveals encouraging results. However, concerns about long-term safety including serious adverse events, warrant further investigation. While hold promise for treating obesity PCOS, issues may limit their utility.

Language: Английский

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Implications of Pregnancy on Cardiometabolic Disease Risk: Preeclampsia and Gestational Diabetes

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 327(3), P. C646 - C660

Published: July 16, 2024

Cardiometabolic disorders, such as obesity, insulin resistance, and hypertension, prior to within pregnancy are increasing in prevalence worldwide. Pregnancy-associated cardiometabolic disease poses a great risk the short- long-term well-being of mother offspring. Hypertensive pregnancy, notably preeclampsia, well gestational diabetes major diseases growing result prevalence. The mechanisms whereby diabetes, other comorbidities lead preeclampsia incompletely understood continually evolving literature. In addition, novel therapeutic avenues currently being explored these patients offset cardiometabolic-induced adverse outcomes preeclamptic pregnancies. this review, we discuss emerging pathophysiological context most recent preclinical clinical updates pathogenesis treatment conditions.

Language: Английский

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Current views on etiology, diagnosis, epidemiology and gene therapy of maturity onset diabetes in the young

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 20, 2025

MODY, or maturity-onset diabetes of the young, is a group monogenic diseases characterized by autosomal dominant inheritance non-insulin-dependent form that classically manifests in adolescence young adults under 25 years age. MODY rare cause diabetes, accounting for 1% all cases, and often misdiagnosed as type 1 2 diabetes. It great importance to accurately diagnose this allows most appropriate treatment patients facilitates early diagnosis them their families. This disease has high degree phenotypic genetic polymorphism. The prevalent forms are attributed mutations three genes: GCK (MODY 2) (HNF)1A/4A 3 1). remaining subtypes, which less prevalent, have been identified next generation sequencing (NGS) last decade. Mutations gene result asymptomatic, stable fasting hyperglycemia, does not require specific treatment. HNF1A HNF4A genes pancreatic β-cell dysfunction, turn causes hyperglycemia. leads diabetic angiopathy. commonly prescribed drugs hyperglycemia sulfonylurea derivatives. Nevertheless, with advancing age, some may insulin therapy due development resistance drugs. strategy still an experimental approach, it unlikely be widely used clinic peculiarities structure polymorphism clinical variability even within same disease. Furthermore, there lack clear gene-phenotypic correlations, quite satisfactory curability majority patients. review presents main characteristics mutation spectrum common rarer detailed analysis field application AVV vectors correction resistance.

Language: Английский

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Role of Glucagon-Like Peptide-1 Receptor Agonists in People With Infertility and Pregnancy

Obstetrics and Gynecology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Obesity is a chronic condition that causes significant morbidity and mortality in people the United States around world. Traditional means of weight loss include diet, exercise, behavioral modifications, surgery. New medications, glucagon-like peptide-1 receptor agonists, are revolutionizing management but have implications for fertility pregnancy. associated with infertility may affect response to ovulation induction medications. In pregnancy, obesity increases risks spontaneous abortion, birth defects, gestational diabetes, hypertensive disorders cesarean delivery, stillbirth. Lifestyle changes alone not improved outcomes. Glucagon-like agonists new medications targeting gut hormones can help achieve their goals contraindicated Obstetrician-gynecologists should work patients manage these before they become pregnant, between pregnancies, after delivery.

Language: Английский

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