Commentary on Qeadan et al.: Leveraging opportunities to expand the substance use disorder treatment arsenal DOI Creative Commons
Ty S. Schepis

Addiction, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

While awaiting randomized controlled trial results, analyses of electronic heath record data can further our understanding the effectiveness glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists for substance use disorders without medication treatment options, such as cannabis stimulant disorders. Many efficacious behavioral treatments exist (SUDs), but these often have important limitations. Behavioral options that include cognitive–behavioral therapy contingency management effectively treat a variety SUDs [1, 2], interventions are limited by their expense, availability trained clinicians motivation time commitment required those seeking [3, 4]. SUD medications similarly impacted access, cost motivational barriers [3], with structural in some countries [5, 6] resulting from unique concerns about potential misuse or diversion highly effective opioid agonist [7]. Along limitations, many individuals may not benefit specific treatment, highlighting need ongoing development. Qeadan et al. [8] provide intriguing evidence linked to reduced incidence alcohol intoxication overdose disorder disorder, respectively. Using health (EHR) US sample, they found 50% reduction medical visits 40% overdose. When combined animal [9] emerging more mixed human experimental observational studies [10-12], al.'s methodological perspective strengthens case double-blind, trials (RCTs) evaluate SUD. Indeed, diverse sets methodologies samples support GIP GLP-1 increase RCTs, addictions research needs perspectives truly understand causes develop Medication alcohol, nicotine/tobacco dependence be reasons noted above, at least exist. This is disorders, where no approved available [13-15]. Thus, clear direction future test efficacy psychostimulant ultimate standard will double-blind researchers should also consider using administrative outcomes Together re-analysis existing study data, rapid evaluation EHR motivate inform design RCTs ultimately determine utility cannabis, other SUDs. In addition evaluations GIP-1 offer rich opportunity reuse past, only very perceptive could identify promising repurposing SUD, exponential increases computing power newer machine-learning artificial intelligence methods, opportunities large-scale exploratory investigations candidates later hypothesis-driven evaluation. Ultimately, caution needed when approaching Leggio [16] highlighted. Regulatory approval necessary step before any [16], meantime investigate exploration large therapies move forward advance scope Ty S. Schepis: Conceptualization; funding acquisition; writing - original draft. article was funded Department Health Human Services, National Institutes Health, Institute on Drug Abuse (R01DA043691). T.S.S. receives Abuse, Substance Mental Services Administration Food Administration.

Language: Английский

Weight loss therapy and addiction: increased risk after bariatric surgery but reduced risk with GLP-1 receptor agonists DOI
André Scheen

Diabetes & Metabolism, Journal Year: 2025, Volume and Issue: unknown, P. 101612 - 101612

Published: Jan. 1, 2025

Language: Английский

Citations

1
Re: The association between glucose‐dependent insulinotropic polypeptide and/or glucagon‐like peptide‐1 receptor agonist prescriptions and substance‐related outcomes in patients with opioid and alcohol use disorders: A real‐world data analysis DOI Open Access
Yanning Wang, Almut G. Winterstein

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

Published: Jan. 24, 2025

We appreciate the study by Qeadan et al. [1] suggesting an association between glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon-like peptide-1 receptor agonists (GLP-1) and lower rates of opioid overdose alcohol intoxication among patients with use disorder (OUD) (AUD). Although promising, several methodological limitations warrant critical discussion. A central issue lies in definition entry for comparator group, using a random date following diagnosis OUD or AUD. This approach introduces potential bias failing to align clinical trajectories groups. Unlike defined index time GIP/GLP-1 which coincides specific intervention (initiation therapy), group lacks similar context. Based on plotted incidence (Figure 1), it appears that timing post OUD/AUD is skewed toward acute substance use-related care, peaks only 1 month after entry. In contrast, treatment was likely initiated during stable periods, far from management phase, illustrated flat outcome rates, those control first year follow-up. To better this time-related [2, 3], matching intervals both groups would have been desirable. Further, even if were aligned, choosing non-active design subject residual confounding differences healthcare engagement, treatment-seeking behaviors comorbidities [4]. notion reflected substantial patient characteristics, shift adjusted interval rate ratios null weakened protected effect when restricting analysis history Type-2 diabetes obesity. authors various covariates, unmeasured confounders related disease severity, access provider practices could still influence results. subgroup active [5, 6], such as initiating other treatments [e.g. sodium-glucose cotransporter-2 (SGLT-2) inhibitors sulfonylureas], help minimize indication, because they ensure represent populations similarly engaged facing comparable decisions. Finally, electronic health record data adds additional complexity gaps continuity [7-10]. Notably, less insurance, raises concerns about differential exposure, confounder measurement two The conducted sensitivity analyses requiring 2 years follow-up, exclude who died introduce selection bias. As shown supplemental table 15, non-significant cohorts 2-year Accounting defining censoring events, including medication discontinuation no capture, primary time-to-event analyses, will improve validity. Adherence transparency reporting standards pharmacoepidemiological studies real-world [11-13] addressing future research warranted strengthen validity findings. Yanning Wang: Conceptualization; methodology; writing—original draft; writing—review editing. Almut G. Winterstein: A.G.W. reported receiving grant funding MSD, National Institutes Health, United States Food Drug Administration, Centers Disease Control Prevention, Agency Healthcare Research Quality, Bill Melinda Gates Foundation State Florida consulting speaker fees Ipsen, Bayer AG, Arbor Pharmaceuticals LLC, Novo Nordisk, Lykos Syneos Health outside submitted work. N/A

Language: Английский

Citations

1
Avoiding a new US “war on drugs” DOI
Vincent Guilamo‐Ramos, Adam Benzekri, Landon Wilson

et al.

BMJ, Journal Year: 2025, Volume and Issue: unknown, P. r225 - r225

Published: Feb. 4, 2025

Language: Английский

Citations

1
D’une longue pénurie thérapeutique au triomphe des nouvelles classes d’antidiabétiques dans des maladies non métaboliques DOI

Serge Halimi

Médecine des Maladies Métaboliques, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Citations

0
Association of Glucagon-Like Peptide-1 Receptor Agonist with Progression to Liver Cirrhosis and Alcohol-Related Admissions in Patients with Alcohol Use Disorder and Diabetes: A Retrospective Cohort Study DOI
Feras Al-Moussally, Saud Khan,

Vinay Katukuri

et al.

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

Published: April 13, 2025

Language: Английский

Citations

0
Therapeutic Effects of GLP-1 Receptor Agonists and DPP-4 Inhibitors in Neuropathic Pain: Mechanisms and Clinical Implications DOI Creative Commons
Yaswanth Kuthati,

Venkata Naga Goutham Davuluri,

Chih‐Shung Wong

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 622 - 622

Published: April 26, 2025

Glucagon-like peptide-1 (GLP-1) is a peptide hormone secreted by the small intestine upon food intake. GLP-1 enhances insulin secretion, suppresses glucagon release, and promotes satiety, resulting in reduced consumption subsequent weight loss. Endogenous has very short half-life rapidly degraded enzyme dipeptidyl-peptidase-IV (DPP-4). To address this limitation, receptor agonists (GLP-1RAs) DPP-4 inhibitors (DPP-4is) were developed have demonstrated potency clinical practice. In recent years, GLP-1RA DPP4-i therapies are known to pleiotropic effects, such as reduction oxidative stress, autophagy regulation, metabolic reprogramming, enhancement of anti-inflammatory signaling, regulation gene expression, being neuroprotective. These effects imply therapeutic perspective for DPP-4i neuropathic pain treatment. Preclinical studies increasingly support hypothesis that these may alleviate targeting multiple mechanisms induce pain, inflammation, mitochondrial dysfunction. This review explores which GLP-1RAs DPP-4is pain. It also highlights current advancements incretin research, focusing on DPP-4-is

Language: Английский

Citations

0
Anti-consumption agents: Tirzepatide and semaglutide for treating obesity-related diseases and addictions, and improving life expectancy DOI Creative Commons
James H. O’Keefe,

William Grant Franco,

Evan L. O’Keefe

et al.

Progress in Cardiovascular Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

3
Response to Wang and Winterstein: Robustness of GIP/GLP‐1 RA findings in substance use disorders DOI Open Access
Fares Qeadan,

Ashlie McCunn,

Benjamin Tingey

et al.

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

Published: Feb. 3, 2025

We appreciate the thoughtful commentary by Wang and Winterstein [1] on our study [2], which provides an opportunity to address their concerns further elucidate robustness of findings. Regarding concern about comparator group lacking a defined clinical context, this issue was carefully considered. To minimize biases from misaligned trajectories, we assigned index dates for randomly within observational window, per Hernan Robins [3]. In response [1], conducted additional analysis aligning time intervals between initial opioid use disordert (OUD)/alcohol disorder (AUD) diagnosis entry both groups. The adjusted incidence rate ratio (aIRR) 95% CI overdose among those prescribed GIP/GLP-1 receptor agonists (RAs) compared not 0.52 (0.29–0.92) OUD cohort. Similarly, alcohol intoxication, aIRR (95% CI) 0.53 (0.33–0.87) AUD These findings align closely with original results 0.60 (0.43–0.83) 0.50 (0.40–0.63), underscoring conclusions. residual confounding because healthcare engagement, treatment-seeking behaviors comorbidities, used comprehensive strategies these challenges. Our regression models baseline demographic, utilization variables [4]. Additionally, inverse probability treatment weighting (IPTW) balance measured confounders bias [5]. Sensitivity analyses excluding patients prior or intoxication histories demonstrated that protective associations remained stable, rather than being driven differential substance non-prescribed patients. Adjustment severity markers confirmed beyond indication [6]. Stratified revealed no substantial differences in effect estimates subgroups Type 2 diabetes obesity, confirming consistency across populations. respectfully refute statement 'shifted toward null' 'weakened effect' when restricted obesity. observed aIRRs were nearly identical, overlapping CIs confirm consistent [7], reminding commentators distinction absolute statistical differences. Furthermore, focused general OUD/AUD population limited comparing different diabetic medications. Assertions active versus non-active comparators are, therefore, scope analysis. also addressed unmeasured confounders, including proxies disease severity, access provider practices, through rigorous methodological approaches such as IPTW, random-effects modeling sensitivity [8, 9]. included comorbidity burden, overdose/intoxication history concurrent mental health disorders. analyses, adjusting ICU emergency department visits 1 month diagnosis, yielded [e.g. = (0.44–0.84); 0.51 (0.40–0.63)]. Moreover, previously hospital system random account institutional multilevel, hierarchical provider-level variability [10], similar outcomes 0.57 (0.40–0.80); 0.55 (0.43–0.70)]. data continuity loss follow-up incorporating 'time-on-study' into all calculations applying alternative approaches, Andersen-Gill recurrent events [11]. Extended reaffirmed effects RAs. some required have 1/2 years follow-up, whereas others, inclusion stopped ensure at least follow-up. For 2-year statistically significant, approached significance (aIRR 0.70 [0.46–1.06]; p 0.09), likely reflecting reduced power smaller n, trend consistent. Claims regarding insurance, exposure outcome measurement overlooked performed. example, specifically accounted insurance main matched it along other analysis, yielding results. contribute growing evidence potential role RAs addiction medicine, providing strong foundation future prospective research. value engagement contribution advancing Constructive dialogue is essential refining methodologies ensuring reliability real world (RWD) studies [12]. None.

Language: Английский

Citations

0
GLP-1 Receptor Agonists: Encouraging Signals for Treating Alcohol Use Disorder DOI Creative Commons
Marlene C. Lira, Eileen Barrett, Maitreya Coffey

et al.

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

Published: April 24, 2025

Language: Английский

Citations

0
The role of the gut-brain axis in bariatric surgery DOI
Tyler Cook, Maigen Bethea, Darleen A. Sandoval

et al.

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 92, P. 103041 - 103041

Published: May 10, 2025

Language: Английский

Citations

0