Glucagon-like peptide-1 receptor agonists and risk of suicidality among patients with type 2 diabetes: active comparator, new user cohort study

BMJ, Journal Year: 2025, Volume and Issue: unknown, P. e080679 - e080679

Published: Feb. 26, 2025

Abstract Objective To determine whether the use of glucagon-like peptide-1 (GLP-1) receptor agonists is associated with an increased risk suicidal ideation, self-harm, and suicide among patients type 2 diabetes compared dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Design Active comparator, new user cohort study. Setting Primary care practices contributing data to UK Clinical Practice Research Datalink linked Hospital Episodes Statistics Admitted Patient Care Office for National Death Registration databases. Participants Patients diabetes. Exposures Two cohorts were assembled, first composed who started continued on GLP-1 DPP-4 between 1 January 2007 31 December 2020 second SGLT-2 2013 2020. Both followed until 29 March 2021. Main outcome measures The primary was suicidality, defined as a composite suicide. Secondary outcomes each these events considered separately. Propensity score fine stratification weighted Cox proportional hazards models fitted estimate hazard ratios 95% confidence intervals (CIs) average treatment effect treated patients. Results included 36 082 agonist users (median follow-up 1.3 years) 234 028 inhibitor 1.7 years). In crude analyses, incidence suicidality (crude rates 3.9 v 1.8 per 1000 person years, respectively; ratio 2.08, CI 1.83 2.36). This decreased null value after confounding factors accounted (hazard 1.02, 0.85 1.23). 32 336 1.2 96 212 Similarly, in analyses 4.3 2.7 years; 1.60, 1.37 1.87) but not (0.91, 0.73 1.12). Similar findings observed when analysed separately both cohorts. Conclusions this large study,

Language: Английский

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The Effect of Glucagon-Like Peptide-1 Receptor Agonists on Measures of Suicidality A Systematic Review

Journal of Psychiatric Research, Journal Year: 2025, Volume and Issue: 183, P. 112 - 126

Published: Feb. 6, 2025

Reports submitted to the FDA and EMA suggest that Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) may be associated with an elevated risk of suicidality. To ascertain this association across available pharmacovigilance cohort studies, Pubmed, Medline, Cochrane Library, PsychInfo, Embase, Scopus, Web Science were searched from database inception November 20, 2024 in accordance PRISMA guidelines. A manual search using Google Scholar was also conducted identify additional studies. Cohort studies assessed for quality Newcastle-Ottawa Scale. We endeavored define operationalize suicidality as suicide ideation (SI), attempts (SA), completion (SC), cases where study authors failed separate these three dimensions, term "suicidality" applied. 22 meeting inclusion criteria comprised (n = 10) 12) identified. Pharmacovigilance indicate semaglutide liraglutide are disproportionate reporting SI. Results GLP-1 RAs not consistently increase any aspect suicidality; instead, some agents decreased SI SA. There is inadequate information whether causality exists linking Ongoing vigilance further required inform if possibility exists. Practitioners prescribing should vigilant emergence aware higher mental illness persons who would candidates (e.g. Type 2 Diabetes, obesity).

Language: Английский

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Glucagon-Like Peptide-1 Receptor Agonists and Risk for Depression in Older Adults With Type 2 Diabetes

Annals of Internal Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown potential antidepressant effects, population studies yield inconsistent results. To compare the risk for depression in older adults with type 2 diabetes (T2D) initiating treatment GLP-1RAs versus sodium-glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 (DPP4is). Target trial emulation study. U.S. National Medicare administrative data from January 2014 to December 2020. Adults aged 66 years T2D a GLP-1RA were matched 1:1 on propensity score those either an SGLT2i DPP4i. The primary end point was incident depression. Cox proportional hazards regression models used estimate hazard ratio (HR) 95% CI within groups. A total of 14 665 pairs included cohort SGLT2is; rate difference between users and 3.48 (95% CI, -0.81 7.78) per 1000 person-years, HR 1.07 (CI, 0.98 1.18). In DPP4is (13 711 pairs), -5.78 -10.49 -1.07) 0.90 0.82 0.98). Unmeasured confounders (such as hemoglobin A1c levels body mass index), outcome misclassification, limited generalizability all (for example, younger populations without receiving drug obesity treatment). Among T2D, incidence relatively low. Use associated modestly lower compared use DPP4is, but not SGLT2is. Institute Diabetes Digestive Kidney Diseases Institutes Health.

Language: Английский

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Risk of depression and dementia among individuals treated with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists

Current Opinion in Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Purpose of the review To whether sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists decrease risk depression, suicidal ideation cognitive impairment in later life. Recent findings The results studies using information derived from large registries administrative health datasets suggest that GLP-1 (RAs) increase suicidality, although have been inconsistent. One nested-case control study reported SGLT2i decreases depression among adults with diabetes, a small trial empagliflozin provided supportive evidence. Several observational RAs dementia risk, target finding greater benefit associated use compared other medicines commonly used to manage diabetes. Summary RA may effects these on mood not as well explored, but there are concerns about potential increased suicidality users. Prescription bias could explain some associations, so robust evidence is now needed confirm or dismiss findings.

Language: Английский

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GLP-1 receptor agonists and suicidality

BMJ, Journal Year: 2025, Volume and Issue: unknown, P. r351 - r351

Published: Feb. 26, 2025

Language: Английский

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Assessing the Antidepressant Effects of GLP-1 Receptor Agonists Using Mendelian Randomization

Asian Journal of Psychiatry, Journal Year: 2025, Volume and Issue: 106, P. 104416 - 104416

Published: Feb. 28, 2025

Language: Английский

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Weight Reduction with GLP-1 Agonists and Paths for Discontinuation While Maintaining Weight Loss

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 408 - 408

Published: March 13, 2025

Worldwide, nearly 40% of adults are overweight and 13% obese. Health consequences excess weight include cardiovascular diseases, type 2 diabetes, dyslipidemia, increased mortality. Treating obesity is challenging calorie restriction often leads to rebound gain. Treatments such as bariatric surgery create hesitancy among patients due their invasiveness. GLP-1 medications have revolutionized loss can reduce body in obese by between 15% 25% on average after about 1 year. Their mode action mimic the endogenous GLP-1, an intestinal hormone that regulates glucose metabolism satiety. However, drugs carry known risks and, since use for recent, may unforeseen well. They a boxed warning people with personal or family history medullary thyroid carcinoma multiple endocrine neoplasia syndrome 2. Gastrointestinal adverse events (nausea, vomiting, diarrhea) fairly common while pancreatitis obstruction rarer. There be lean mass well premature facial aging. A significant disadvantage using these high rate regain when they discontinued. Achieving success pharmacologic treatment then weaning avoid future negative effects would ideal.

Language: Английский

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Suicide and Self-Harm Events With GLP-1 Receptor Agonists in Adults With Diabetes or Obesity

JAMA Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Importance Bariatric surgery, once the criterion standard in obesity treatment, has a small but concerning association with increased suicidality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed to treat diabetes, now provide substantial efficacy treatment of obesity. However, concerns risk suicidality these medicines have been raised. Objective To evaluate and self-harm randomized, placebo-controlled trials GLP-1 RAs adults diabetes or Data Sources MEDLINE, Embase, ClinicalTrials.gov, Cochrane databases were systematically searched from inception August 29, 2023. Study Selection Reports randomized clinical (RCTs) lasting 6 more months comparing placebo for published peer-reviewed journals identified. Two independent reviewers screened all search-identified studies inclusion. Records outcomes queried primary papers, ClinicalTrials.gov entries, corresponding authors. Extraction Synthesis researchers abstracted data assessed quality validity using PRISMA guidelines. pooled random-effects models. Main Outcomes Measures Pooled incidence completed attempted suicide, occurrences suicidal ideation, self-harm. Results A total 27 144 RCTs meeting inclusion criteria recorded suicide and/or self-harm-related events included 32 357 individuals receiving 046 treated placebo, over 74 740 68 095 person-years follow-up, respectively. Event was very low RA (0.044 per 100 person-years) (0.040 groups, no statistically significant difference (rate ratio [RR], 0.76; 95% CI, 0.48-1.21; P = .24). Subgroup analyses did not suggest differences based on status used. Five considered at bias due loss than 5% participants follow-up. Otherwise, found be heterogeneous nor high bias. Conclusions Relevance There is unlikely an increase suicide-related adverse among within context RCTs. While findings may further ease about effects, continued monitoring warranted identify particular patients who as extended use expands.

Language: Английский

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INTEGRATE: international guidelines for the algorithmic treatment of schizophrenia

The Lancet Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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GLP-1 receptor agonists efficacy in managing comorbidities associated with diabetes mellitus: a narrative review

Journal of Diabetes & Metabolic Disorders, Journal Year: 2025, Volume and Issue: 24(1)

Published: April 1, 2025

Language: Английский

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