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Research papers are like investigative journalism. Just as journalists gather facts to craft a story, students collect information, analyze it, and present their findings. But here’s the thing: it can be tough, especially for beginners.
First, defining a research problem is tricky. You’ve got to align with your school’s criteria, considering the significance, relevance, and feasibility of research.
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The research world is vast, with thousands of scientific journals and millions of papers published yearly. Researchers must publish to progress in their careers, which means more pressure.
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It’s a good idea to get a bird’s eye on the process before you buy a research paper online. Here’s how our process works:
Here are some common types of research paper assignments with brief descriptions of each:
In this type of paper, you analyze a topic or issue by presenting different viewpoints and arguments, often requiring critical thinking and a balanced approach.
Argumentative papers require you to take a stance on a specific issue and present evidence to support your position while addressing counterarguments.
This one explains a topic, process, or concept. They require clear and concise writing to inform the reader.
Students often buy research papers for a literature review. It summarizes and evaluates existing research on a particular subject, highlighting key findings, gaps, and trends in the chosen area.
In experimental research, you conduct an experiment or study and present the methodology, results, and conclusions. These papers are common in scientific and social science disciplines.
You design and administer surveys to collect data, analyze responses, and conclude a specific topic or issue.
Case study papers delve deep into a single case or instance, exploring it comprehensively and drawing lessons or insights from it.
The virtual realm is flooded with countless options. However, we strongly recommend selecting a trustworthy and expert service that assembles a team of knowledgeable writers and editors. Look out for features like money-back guarantees and endorsements from globally recognized financial institutions – these are added advantages.
Absolutely. Your privacy is our top priority. Rest assured that nobody besides you and our service provider will ever know about your research paper purchase. Our privacy policy explicitly prohibits sharing personal information with third parties, including educational institutions like schools, colleges, and universities.
Look no further. CustomWriting offers a winning combination of expert writers, robust plagiarism checks, budget-friendly rates, and swift delivery. Your research paper dreams start here!
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Expertly crafted APA or MLA research papers from qualified writers in 35+ academic areas
36 thousands Papers written annually • Time-tested
Specializing in about 85 subject areas
Originality report • Strictly confidential
In our service, we've gathered a vast group of skilled writers ready to assist you in enhancing your performance.
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Finding a good academic writer is a true challenge. On the one hand, the market seems overcrowded, with endless experts vying for a position and claiming they are the best; on the other hand, many students complain about getting poor writing services. When you contact a company with the words, “I’d like to pay someone to write my paper for me,” you expect superior service. Our job is to make certain that you receive it. From the start, we make our recruiting demands clear: we are interested in top specialists with a strong academic background. These are educators, professional researchers, scholars, and talented writers who completed their education and gained relevant experience. They all speak English as their first language, and they passed various tests that proved the extent of their skills to us.
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We are pleased to share examples of writing that we've done for our clients.
While AI is becoming even more popular today, we ignore its existence entirely. Our company focuses on human writing and expertise because only this approach can guarantee the most brilliant results. We choose the best experts for this goal, connecting you with someone who has appropriate qualifications and experience with your subject. Both writers and managers adhere to clients’ instructions: if they have questions, they ask them ASAP to get started as soon as possible. When they begin their writing process, the experts thoroughly research, selecting suitable sources and combining them with their ideas. Their analysis is spectacular, just like their time management skills, so you’ll get a great and original paper right on time.
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Note that we ask for pleasantly affordable prices. The lowest cost is $10.78. If your rate is higher and you don’t like it, consider changing some factors. For instance, set a longer deadline — this always lowers the price, or pick an easier academic level. High school papers are cheaper than college or university essays.
+ APA, MLA, Chicago, Turabian citation styles or any other of your choice
We are constantly expanding the number of our benefits for the sake of our customers. If you came to us with a wish, “Please write my research paper for me today,” you will get that and more! This is what we can do for you:
Have a look at our other advantages.
🏆 Many top writers at your service | We have over 500 top-notch experts ready to handle your task |
✅ Strong plagiarism-free policy | We’re committed to producing 100% original content |
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✅ No hidden charges | Our clients enjoy complete payment transparency |
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Since our writers have excellent qualifications and received higher education, handling any formatting style is fine. They are familiar with all styles, from MLA to Chicago, APA, and others. Order any of them or send us a template. We’ll adapt to it momentarily.
TrustMyPaper works with different subjects and academic levels. Whether it’s English, Business, Engineering, Sociology, Religion, or anything else, we’ll find the right expert for you. Students can buy nursing and medical papers, Chemistry lab reports, and college applications — we’ll help them with everything. You can order projects on a high school, college, Master’s, or Doctoral level. Also, did you know that your writer won’t receive payment from you until you confirm that you like the essay they provided? That’s right, we withhold the money to ensure we meet your demands. This adds safety to your client experience with us.
No one will learn that you chose to buy a research paper from our firm. Yes, you share some information about yourself when placing an order, but we never disclose or share it with random parties. We adhere to rigid safety standards in all our work processes, so there is no reason to worry.
Some students wonder how ethical it is to buy custom research papers. If this is your first order, you might have the same question. You’ll be happy to know that ordering essays is entirely legal — you purchase academic assistance akin to tutoring. You can use them as samples, relying on them to show you what an accurate structure, research, and formatting look like. The works we provide serve as your inspiration that pushes you into creating your works.
Before buying a research paper, reading reviews and seeing what previous clients thought about a service makes sense. We invite you to do this with our firm as well. Check what other TrustMyPaper reviews say, and you’ll feel relief because most of them are positive! We invest a ton of effort into our papers, and our clients reap the benefits of it. Our service is instantly available, original, and timely; it has the highest quality, and we are certain you'll love your research paper as much as your fellow students did.
If complex research is looming ahead and you’d love to get some assistance, contact TrustMyPaper and describe your request in detail. We offer low rates for top writing quality and multiple safety guarantees. Total privacy, revisions, and refunds guard your satisfaction while our operators are constantly on high alert, ready to rescue you immediately. Give yourself a chance to relax. Give your research to us, and watch us do our academic magic with it!
When you buy research papers online, we guarantee your confidentiality from start to finish. Ask for a plagiarism report, and we will send it to you immediately; check your research paper via any other plagiarism checker, and you’ll see its 100% originality rate.
No, it is not. As our policies stipulate, students buy a research paper as a sample for gaining inspiration and seeing what an ideal research paper looks like. There is nothing illegal about it.
Our company asks for fully affordable prices: one page will cost you just $10.78. There is also a great 17% discount for new clients: apply it if you’re buying a custom research paper for the first time.
Yes, you can pay for your order with your credit card. We don't care about Visa, American Express, MasterCard, or Discover — just select the method you trust and buy the essay you want.
Of course, we do. Being the best site to buy research papers online from, we secure your personal information with the help of various protocols. You are not taking risks, as no one will learn about your order.
TrustMyPaper guarantees that all of your personal and financial information will be safe. Our customers' order and payment details are protected by the highest level of security.
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The Writing Planet
50 % off on all orders
In the vast realm of academia, research papers stand as the cornerstone of scholarly pursuit. They represent not just an assignment but a gateway to knowledge, critical thinking, and academic excellence. However, the journey towards crafting a stellar research paper can often be daunting, filled with challenges and hurdles. This is where the concept of custom research papers for sale online comes into play, offering students a lifeline in their academic endeavors. At The Writing Planet, we understand the importance of providing affordable yet top-notch research papers, tailored to meet the unique needs of every student.
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When you buy a research paper, quality reigns supreme. Seek out reputable platforms that offer custom-written research papers by top-notch writers with subject expertise. An excellent research paper should showcase meticulous research, critical analysis, and impeccable formatting. Look for services that boast a team of professional research paper writers dedicated to delivering excellence.
One-size-fits-all doesn’t apply to academic papers. Ensure that your chosen service offers bespoke solutions tailored to your specific requirements. A well-crafted research paper should reflect your academic style and adhere to the guidelines provided by your institution. Opt for platforms that prioritise originality, crafting each paper from scratch to prevent any plagiarism concerns.
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Submit the order form.
Provide you personal and academic details at the first step of the order form to get prices.
Provide order specifics including the project title, desired referencing style and more.
Make the payment at the final step to confirm your order. You can pay in full or installments.
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Our Writers
Explore free research paper samples crafted by ResearchProspect’s seasoned writers so you know the quality we are capable of producing before placing your order.
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Yes, it is ethical if used responsibly. ResearchProspect emphasises its papers are for guidance and research purposes, promoting learning. They adhere to academic integrity and discourage submitting the work as-is, ensuring that students learn from the materials provided.
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ResearchProspect’s strengths lie in its unwavering commitment to quality, customisation, and customer satisfaction. Their expert writers, attentive customer support, stringent quality control, and transparent communication make them the ideal choice. Trust ResearchProspect for well-crafted, academically sound, and personalised research papers.
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The flow diagram shows the cohort selection for the analysis of the risk of nonarteritic anterior ischemic optic neuropathy (NAION) in patients treated with semaglutide vs a non–glucagon-like peptide 1 receptor agonist (GLP-1 RA) either for type 2 diabetes or for overweight or obesity.
a Matching criteria included propensity score matching on age, sex, hypertension, type 2 diabetes, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease as well as lack of chronic kidney disease, personal or family history of multiple endocrine neoplasia type 2, thyroid tumors, or pancreatitis status.
Survival probabilities are shown for NAION in patients with type 2 diabetes prescribed semaglutide vs a matched cohort of patients prescribed non–glucagon-like peptide 1 receptor agonist (GLP-1 RA) antidiabetic medications (A) and in patients who were overweight or obese and prescribed semaglutide vs a matched cohort of patients prescribed non–GLP-1 RA antiobesity medications (B). HR indicates hazard ratio.
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Hathaway JT , Shah MP , Hathaway DB, et al. Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmol. Published online July 03, 2024. doi:10.1001/jamaophthalmol.2024.2296
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Question Are prescriptions for semaglutide associated with an increased risk of nonarteritic anterior ischemic optic neuropathy (NAION) in patients with type 2 diabetes or patients who are overweight or obese?
Findings This matched cohort study of 16 827 patients revealed higher risk of NAION in patients prescribed semaglutide compared with patients prescribed non–glucagon-like peptide receptor agonist medications for diabetes or obesity.
Meaning The findings suggest a potential risk of NAION associated with prescriptions for semaglutide, but future study is required to assess causality.
Importance Anecdotal experience raised the possibility that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) with rapidly increasing use, is associated with nonarteritic anterior ischemic optic neuropathy (NAION).
Objective To investigate whether there is an association between semaglutide and risk of NAION.
Design, Setting, and Participants In a retrospective matched cohort study using data from a centralized data registry of patients evaluated by neuro-ophthalmologists at 1 academic institution from December 1, 2017, through November 30, 2023, a search for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code H47.01 (ischemic optic neuropathy) and text search yielded 16 827 patients with no history of NAION. Propensity matching was used to assess whether prescribed semaglutide was associated with NAION in patients with type 2 diabetes (T2D) or overweight/obesity, in each case accounting for covarying factors (sex, age, systemic hypertension, T2D, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease) and contraindications for use of semaglutide. The cumulative incidence of NAION was determined with the Kaplan-Meier method and a Cox proportional hazards regression model adjusted for potential confounding comorbidities. Data were analyzed from December 1, 2017, through November 30, 2023.
Exposures Prescriptions for semaglutide vs non–GLP-1 RA medications to manage either T2D or weight.
Main Outcomes and Measures Cumulative incidence and hazard ratio of NAION.
Results Among 16 827 patients, 710 had T2D (194 prescribed semaglutide; 516 prescribed non–GLP-1 RA antidiabetic medications; median [IQR] age, 59 [49-68] years; 369 [52%] female) and 979 were overweight or obese (361 prescribed semaglutide; 618 prescribed non–GLP-1 RA weight-loss medications; median [IQR] age, 47 [32-59] years; 708 [72%] female). In the population with T2D, 17 NAION events occurred in patients prescribed semaglutide vs 6 in the non–GLP-1 RA antidiabetes cohort. The cumulative incidence of NAION for the semaglutide and non–GLP-1 RA cohorts over 36 months was 8.9% (95% CI, 4.5%-13.1%) and 1.8% (95% CI, 0%-3.5%), respectively. A Cox proportional hazards regression model showed higher risk of NAION for patients receiving semaglutide (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29); P < .001). In the population of patients who were overweight or obese, 20 NAION events occurred in the prescribed semaglutide cohort vs 3 in the non–GLP-1 RA cohort. The cumulative incidence of NAION for the semaglutide vs non–GLP-1 RA cohorts over 36 months was 6.7% (95% CI, 3.6%-9.7%) and 0.8% (95% CI, 0%-1.8%), respectively. A Cox proportional hazards regression model showed a higher risk of NAION for patients prescribed semaglutide (HR, 7.64; 95% CI, 2.21-26.36; P < .001).
Conclusions and Relevance This study’s findings suggest an association between semaglutide and NAION. As this was an observational study, future study is required to assess causality.
Nonarteritic anterior ischemic optic neuropathy (NAION) is the second most common form of optic neuropathy and a significant cause of blindness among adults. 1 - 4 Our anecdotal clinical experience motivated us to study whether semaglutide is associated with an increased risk of developing NAION.
Semaglutide (Ozempic; Novo Nordisk) was approved by the US Food and Drug Administration (FDA) in December 2017 to treat type 2 diabetes (T2D) and in December 2022 to treat obesity (typically at higher doses, as Wegovy [Novo Nordisk]). Weekly new-to-brand prescriptions in the United States of these and other glucagon-like peptide receptor agonist (GLP-1 RA) drugs increased by approximately 60% from 2021 to 2023. 5
In major medical centers, neuro-ophthalmologists are most likely to evaluate suspected cases of NAION. This study was designed to capitalize on this expertise by characterizing the risk of NAION among individuals using semaglutide within a neuro-ophthalmology practice at a single academic center.
Following approval by the Massachusetts General Brigham (MGB) Institutional Review Board, we conducted a retrospective, matched cohort study of neuro-ophthalmic patients at Massachusetts Eye and Ear, Boston. Our methods adhered to the Declaration of Helsinki for human research, the regulations of the Health Insurance Portability and Accountability Act, and the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline. 6 Informed consent was not required as this was a retrospective study.
The number of unique patients who had been referred for any presumed neuro-ophthalmology indication and evaluated in our neuro-ophthalmology clinic from December 1, 2017, through November 30, 2023, was determined from the MGB centralized clinical data registry and composed our eligible cohort. Events of NAION were identified by electronic health record query for the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision ( ICD-10 ) code H47.01 (ischemic optic neuropathy) and text search (with terms “NAION” and “non-arteritic anterior ischemic optic neuropathy”). Each identified record was manually reviewed to confirm that the diagnosis of NAION had been rendered by one of our faculty members and to ascertain the time of vision loss. Our manual review confirmed that there was painless vision loss and optic nerve head edema during the acute phase, as per our prior criteria for NAION, 7 although now with more a relaxed age criterion given that our eligible cohort had a median age of 47 years. Patients with NAION prior to our start date were excluded. To mitigate risk of bias due to residual confounding effects, cohorts of T2D and overweight or obesity were analyzed separately; for each cohort, we identified comparative groups not receiving semaglutide. The categorizations of race (as American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, White, declined, patient does not know, race not listed, or unavailable) and sex or gender were self-reported in all cases.
To analyze the hazard ratio (HR) of NAION with respect to T2D, the study population consisted of 710 patients with T2D who were prescribed either semaglutide (n = 194) or non–GLP-1 RA antidiabetic medications (n = 516) ( Figure 1 ). Non–GLP-1 RA medications that we assessed included insulin and analogues, metformin, sulfonylureas, α-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and sodium-glucose transport protein 2 inhibitors.
To analyze the HR with respect to weight, we included patients who were overweight or obese (body mass index of 25-29.9 or >30, respectively [calculated as weight in kilograms divided by height in meters squared]). This study population consisted of 979 patients prescribed either semaglutide (n = 361) or non–GLP-1 RA weight-loss medications (n = 618) ( Figure 1 ). Non–GLP-1 RA antiobesity medications that we assessed included bupropion, naltrexone, orlistat, topiramate, phentermine, and setmelanotide.
To achieve balance between cohorts (prescribed semaglutide or not) for each study population (T2D, and overweight or obese), 1:2 nearest-neighbor propensity score matching (caliper = 0.05) was used to account for demographic factors (sex, age); comorbidities related to NAION (systemic hypertension, T2D, obstructive sleep apnea); indications for use of semaglutide (T2D and obesity) and contraindications of semaglutide (personal or family history of multiple endocrine neoplasia type 2, thyroid cancer, chronic kidney disease, pancreatitis) 8 ; covarying factors related to T2D or to overweight or obesity (hyperlipidemia, coronary artery disease); and use of drugs associated with NAION (phosphodiesterase type 5 inhibitors, 9 amiodarone 10 ). No patient with NAION had received α-interferon. 11 After matching, all standardized mean differences (SMDs) for covariates were less than 0.1, and all SMDs and 2-way interactions among confounding factors were less than 0.15, which in the context of this study using propensity score matching indicates adequate balance between cohorts. Table 1 and Table 2 provide the characteristics of the T2D cohort and the obese or overweight cohort, respectively, with frequency distributions and measures of variability. The primary outcome was the first event of NAION. For all patients who experienced NAION and had been prescribed semaglutide, we confirmed by manual review that the prescribed medication had been dispensed. Although we aimed to match each treated unit with 2 control units in a 1:2 ratio, the actual matching yielded slightly lower ratios due to the relatively small sample sizes.
Patients in the eligible cohorts (T2D and overweight or obese, separately) had differing distributions of baseline characteristics ( Table 1 and Table 2 ). To further isolate and more evenly distribute these characteristics between the eligible (ie, semaglutide vs non–GLP-1) cohorts, we performed secondary analyses with 1:1 nearest-neighbor propensity score matching plus an exact match for variables that differed by 20% or more between the cohorts for each population.
Cumulative incidences of NAION in each cohort were determined with the Kaplan-Meier method to track first events of NAION during follow-up. Person-time was calculated from the first prescription of semaglutide vs non–GLP-1 antidiabetic or weight-control medications in the T2D and overweight or obese populations, respectively, until NAION, death (n = 42 across both populations), or end of the maximal 36-month follow-up period. The Cox proportional hazards regression model with adjustment for matching factors analyzed associations among covariates (described earlier) and the risk of NAION. The ability of our Cox model to discriminate between individuals who did and did not experience NAION was supported by the concordance correlation coefficient. Likelihood ratio testing outperformed a null model that did not incorporate predictors. The Wald test for semaglutide exposure assessed the statistical significance of individual predictors. The log-rank test assessed survival times between cohorts. Schoenfeld residuals and log-log plots for survival curves assessed the proportional hazards assumption and investigated its adequacy. All analyses were conducted with RStudio version 2024.04 statistical software (Posit). All P values were 2-sided and there was no adjustment for multiple analyses.
Our search identified 17 298 unique patients across 6 years. Individuals younger than 12 years (the lower limit of semaglutide exposure) were excluded, which yielded 16 827 patients for analysis ( Figure 1 ). Among the included patients, 710 had T2D (median [IQR] age, 59 [49-68] years; 369 [52%] female) and 979 were overweight or obese (median [IQR] age, 47 [32-59] years; 708 [72%] female).
The study population with T2D included 710 patients ( Figure 1 ). A 1:2 propensity score matching yielded adequate balance between the 2 groups (SMD < 0.1). NAION occurred in 17 patients in the semaglutide cohort vs 6 in the comparative cohort. The median (IQR) age was 57 (49-63) years for the semaglutide cohort and 58 (47-66) years for the nonsemaglutide cohort.
The Kaplan-Meier survival analysis at 36 months showed a cumulative incidence of NAION of 8.9% (95% CI, 4.5%-13.1%) for the semaglutide cohort vs 1.8% (95% CI, 0%-3.5%) for the nonsemaglutide cohort. The mean (SD) follow-up time was 33.3 (1.1) months for the semaglutide group and 34.5 (1.2) months for the nonsemaglutide group. The survival probability for the semaglutide cohort declined steepest over the initial 12 months, with a cumulative incidence of 6.5% (95% CI, 2.7%-10.2%) at year 1 ( Figure 2 A). The Cox proportional hazards regression model showed a higher NAION risk in the semaglutide cohort vs the nonsemaglutide cohort (HR, 4.28; 95% CI, 1.62-11.29; P < .001; concordance coefficient = 0.84). The likelihood ratio test comparing the full model with a reduced model yielded a χ 2 18 statistic of 39.10 ( P = .003). The Wald test for the overall significance of the model produced a χ 2 18 statistic of 25.62 ( P = .008). The score (log-rank) test resulted in a χ 2 18 statistic of 30.08 ( P = .009).
Secondary analyses for baseline variables that differed by 20% or more between the 2 cohorts included an exact match for overweight or obesity and obstructive sleep apnea. The 1:1 propensity and exact matches yielded 264 patients without history of NAION. The Cox proportional hazards regression model showed a higher NAION risk in the semaglutide cohort vs the nonsemaglutide cohort (HR, 4.35; 95% CI, 1.37-13.81; P = .01; concordance coefficient = 0.79). The likelihood ratio test comparing the full model with a reduced model yielded a χ 2 18 statistic of 33.88 ( P = .004). The Wald test for the overall significance of the model produced a χ 2 18 statistic of 23.96 ( P = .008). The score (log-rank) test resulted in a χ 2 18 statistic of 29.10 ( P = .01). These results are not substantially different from those obtained with the Cox analysis based on the 1:2 propensity matching analysis. Male sex also was significant in the Cox model (HR, 2.88; 95% CI, 1.03-8.03; P = .04). Obesity did not significantly change the HR.
The study population of patients who were overweight or obese included 979 patients ( Figure 1 ). A 1:2 propensity score matching yielded adequate balance between the 2 groups (SMD < 0.1). NAION occurred in 20 patients in the semaglutide cohort vs 3 in the comparative cohort. The median (IQR) age was 46 (35-58) years for the semaglutide cohort and 44 (29-59) years for the nonsemaglutide cohort.
The Kaplan-Meier survival analysis at 36 months showed a cumulative incidence of NAION of 6.7% (95% CI, 3.6%-9.7%) for the semaglutide cohort vs 0.8% (95% CI, 0%-1.8%) for the nonsemaglutide cohort. The mean (SD) follow-up time was 34.1 (1.4) months for the semaglutide group and 35.4 (1.0) months for the nonsemaglutide group. The survival probability for the semaglutide cohort declined steepest over the initial 12 months, with a cumulative incidence of 5.5% (95% CI, 2.7%-8.3%) at year 1 ( Figure 2 B). The Cox proportional hazards regression model showed a higher NAION risk in the semaglutide cohort vs the nonsemaglutide cohort (HR, 7.64; 95% CI, 2.21-26.36; P < .001; concordance correlation coefficient = 0.86). The likelihood ratio test comparing the full model with a reduced model yielded a χ 2 18 statistic of 56.20 ( P < .001). The Wald test for the overall significance of the model produced a χ 2 18 statistic of 35.05 ( P = .009). The score (log-rank) test resulted in a χ 2 18 statistic of 56.40 ( P < .001).
Secondary analyses for baseline variables that differed by 20% or more between the 2 cohorts included an exact match for systemic hypertension, T2D, hyperlipidemia, and obstructive sleep apnea. The 1:1 propensity and exact matches yielded 442 patients without history of NAION. The Cox proportional hazards regression model showed a higher NAION risk in the semaglutide cohort vs the nonsemaglutide cohort (HR, 7.28; 95% CI, 1.59-33.34; P = .01; concordance statistic = 0.84). The likelihood ratio test comparing the full model with a reduced model yielded a χ 2 18 statistic of 55.3 ( P < .001). The Wald test for the overall significance of the model produced a χ 2 18 statistic of 34.13 ( P = .04). The score (log-rank) test resulted in a χ 2 18 statistic of 55.11 ( P < .001). These results are not substantially different from those obtained when the Cox analysis was performed using the 1:2 propensity matching analysis. For both primary and secondary analyses, hyperlipidemia in the Cox model increased the risk of NAION, but it was not significant when used independently as an interaction variable.
Our main finding is that prescribed semaglutide is associated with an increased risk of NAION. Despite extensive study, the pathogenesis of NAION has not been fully eludicated. 12 , 13 The incidence of NAION is 2 to 10 cases per 100 000 persons, 2 , 14 making it the second most common cause of blindness due to optic nerve damage (with glaucoma being the most common). The relatively high HRs (4.28 and 7.64 for our T2D and overweight or obese cohorts, respectively) identified by our Cox regression analyses reveal a substantially increased risk of NAION among individuals prescribed semaglutide relative to those prescribed other medications to treat T2D and obesity or overweight. This risk appears not to be due to differences in baseline characteristics between the cohorts.
The study has several strengths. The sample size of 629 NAION cases over 6 years, which is a substantial fraction of expected cases from the Boston area, was relatively large. All diagnoses of NAION were rendered by experienced neuro-ophthalmologists. All records coded as ischemic optic neuropathy were manually reviewed to ensure the clinician had accurately diagnosed NAION. Manual review confirmed that prescribed doses of semaglutide had been dispensed for patients who experienced NAION. Propensity score matching was used to balance cohorts to address potential confounders and reduce selection bias. Also, Cox regression was used to more precisely estimate the association of semaglutide with the risk of NAION.
Nonetheless, did confounding factors influence our estimated risk of developing NAION? Given that semaglutide was first approved to treat T2D, perhaps diabetes or related comorbidities, like obesity, were culprits. Our analyses, however, suggest that plausible confounding factors were not significant contributors to the risk of NAION, although per our Cox regression model, being male might increase the risk of NAION for patients with T2D receiving semaglutide, and having hyperlipidemia might increase the risk of NAION for patients who are overweight or obese and receiving semaglutide. We also used secondary analyses (with exact matching) to further isolate potential confounding influences of baseline variables that differed substantially (≥20%) among the eligible cohorts; however, this approach yielded similar results, supporting the notion that semaglutide, not baseline characteristics, was primarily associated with the heightened risk of NAION. Our survival analyses of both cohorts ( Figure 2 A and B) expose the greatest risk of NAION to be within the first year following prescription of semaglutide, a temporal association that supports a potential drug-induced risk of NAION.
The first 2 injectable GLP-1 RA drugs (Ozempic and Wegovy) accounted for the highest and second highest number of weekly new-to-brand prescriptions in the United States as of April 2023, and 1.7% of all patients in the United States through much of 2023 received prescriptions for semaglutide. 15 New injectable and oral GLP-1 RA formulations are FDA approved, and even more expansive use of these drugs seems likely given their medical benefits 16 - 21 and widespread popularity. If true, our data anticipate increasing numbers of NAION cases related to this class of drugs.
As with any drug, however, therapeutic benefits are inseparable from adverse effects. Related to vision, patients with diabetic retinopathy who received semaglutide incurred a higher risk of exacerbation of the retinopathy, especially with rapid reduction in hemoglobin A 1c levels, 22 and a higher rate of progression of proliferative retinopathy and risk of new-onset macular edema. 23 There has been no prior mention, to our knowledge, of an increased risk of NAION in association with semaglutide, and our study does not inform a mechanism to link semaglutide to NAION. Despite evidence of neuroprotective properties, 24 , 25 expression of the GLP-1 receptor in the human optic nerve 26 and GLP-1 RA–induced enhanced sympathetic nervous system activity might influence optic nerve head perfusion and potentially increase the risk of NAION.
There are several limitations to our study. Our tertiary care institution specializes in ophthalmology and includes a specialized neuro-ophthalmology service that evaluates a large proportion of the region’s NAION cases; therefore, our findings may not be fully generalizable to other settings. Second, our retrospective study does not allow inquiry into potential biases related to decisions about which patients were prescribed semaglutide or which of those patients were referred and evaluated in our neuro-ophthalmology clinic, although notably our hospital system and our service do not exclude any patient based on insurance coverage. Third, our study could not assess whether all patients actually took the drugs as prescribed; nonadherence is a common phenomenon, even for GLP-1 RA drugs, 27 and this may have led to an inaccurate estimation of a semaglutide-associated risk. We did, however, confirm that prescribed doses of semaglutide were dispensed for all patients with NAION. Fourth, our study also is limited in that the severity of confounding factors could not be adequately assessed, as our attempt to substratify the relatively small number of NAION cases in the semaglutide-exposed cohorts (n = 17 and 20) produced wide 95% CIs and less statistical precision. Our analyses were also hindered by laboratory data that were not retrievable from outside institutions. Although we uncovered an association between prescribed semaglutide and NAION, our study did not enable definitive inquiry into relatedness. Although we showed temporal proximity between prescribed semaglutide and NAION, the highest level of confidence to assess relatedness suggested by the FDA also requires establishing risk reduction on stopping a medication and a dose-dependent association. 28 Given that our cohorts were composed of relatively small percentages of patients of races other than White (in particular, of the 16 827 patients in our eligible cohort, 5.7% were listed in the medical record as being Black or African American vs 22.5% of individuals who in 2022 self-identified similarly in the greater Boston area), our results should be considered with caution for the general population, especially given that Black individuals generally have a lower risk of NAION. 29 , 30
This study is the first, to our knowledge, to report an association between semaglutide and NAION, although the design of our study did not enable query into a causal relationship between the two. The best approaches to confirm, refute, or refine our findings would be to conduct a much larger, retrospective, multicenter population-based cohort study; a prospective, randomized clinical study; or a postmarket analysis of all GLP-1 RA drugs. A risk inherent in larger studies, however, is the standard use of ICD-10 diagnostic codes given that there is no ICD-10 code for NAION. The most specific code relevant to NAION is the broader category of ischemic optic neuropathy. Our manual review of records for this study revealed that 40% of cases coded as ischemic optic neuropathy were not actually NAION but rather arteritic ischemic optic neuropathy from giant cell arteritis (which is commonly managed by neuro-ophthalmologists) or other forms of ischemic or nonischemic optic neuropathies. Manual review is not practical for extremely large databases, and the lack of a specific ICD-10 code for NAION (as identified by Hamedani et al 31 ) would be a severe hindrance for any large study. Emerging algorithms 32 , 33 would improve the accuracy of diagnostic coding in larger studies but would not attain the precision of a manual review and might not provide sufficient accuracy to establish a statistical association between use of a drug and occurrence of a relatively uncommon disorder like NAION.
Accepted for Publication: May 8, 2024.
Published Online: July 3, 2024. doi:10.1001/jamaophthalmol.2024.2296
Corresponding Author: Joseph F. Rizzo III, MD, Neuro-Ophthalmology Service, Massachusetts Eye and Ear, Harvard Medical School, 243 Charles St, Boston, MA 02114 ( [email protected] ).
Author Contributions: Drs J. T. Hathaway and Rizzo had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: J. T. Hathaway, Shah, D. B. Hathaway, Zekavat, Cestari, Chwalisz, Estrela, Rizzo.
Acquisition, analysis, or interpretation of data: J. T. Hathaway, Shah, D. B. Hathaway, Zekavat, Krasniqi, Gittinger, Cestari, Mallery, Abbasi, Bouffard, Chwalisz, Rizzo.
Drafting of the manuscript: J. T. Hathaway, Shah, D. B. Hathaway, Zekavat, Krasniqi, Gittinger, Rizzo.
Critical review of the manuscript for important intellectual content: Shah, D. B. Hathaway, Zekavat, Krasniqi, Cestari, Mallery, Abbasi, Bouffard, Chwalisz, Estrela, Rizzo.
Statistical analysis: J. T. Hathaway, D. B. Hathaway, Zekavat.
Administrative, technical, or material support: Shah, D. B. Hathaway, Krasniqi, Gittinger, Mallery, Rizzo.
Supervision: D. B. Hathaway, Cestari, Bouffard, Chwalisz, Rizzo.
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was funded in part by a grant from Research to Prevent Blindness.
Role of the Funder/Sponsor: Research to Prevent Blindness had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Meeting Presentation: This work was presented at the annual meeting of the Association for Research in Vision and Ophthalmology; May 9, 2024; Seattle, Washington.
Data Sharing Statement: See the Supplement .
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Watch CBS News
By Melissa Quinn , Jacob Rosen
Updated on: July 11, 2024 / 9:40 AM EDT / CBS News
Washington — Voters in recent weeks have begun to hear the name "Project 2025" invoked more and more by President Biden and Democrats, as they seek to sound the alarm about what could be in store if former President Donald Trump wins a second term in the White House.
Overseen by the conservative Heritage Foundation, the multi-pronged initiative includes a detailed blueprint for the next Republican president to usher in a sweeping overhaul of the executive branch.
Trump and his campaign have worked to distance themselves from Project 2025, with the former president going so far as to call some of the proposals "abysmal." But Democrats have continued to tie the transition project to Trump, especially as they find themselves mired in their own controversy over whether Mr. Biden should withdraw from the 2024 presidential contest following his startling debate performance last month.
Here is what to know about Project 2025:
Project 2025 is a proposed presidential transition project that is composed of four pillars: a policy guide for the next presidential administration; a LinkedIn-style database of personnel who could serve in the next administration; training for that pool of candidates dubbed the "Presidential Administration Academy;" and a playbook of actions to be taken within the first 180 days in office.
It is led by two former Trump administration officials: Paul Dans, who was chief of staff at the Office of Personnel Management and serves as director of the project, and Spencer Chretien, former special assistant to Trump and now the project's associate director.
Project 2025 is spearheaded by the Heritage Foundation, but includes an advisory board consisting of more than 100 conservative groups.
Much of the focus on — and criticism of — Project 2025 involves its first pillar, the nearly 900-page policy book that lays out an overhaul of the federal government. Called "Mandate for Leadership 2025: The Conservative Promise," the book builds on a "Mandate for Leadership" first published in January 1981, which sought to serve as a roadmap for Ronald Reagan's incoming administration.
The recommendations outlined in the sprawling plan reach every corner of the executive branch, from the Executive Office of the President to the Department of Homeland Security to the little-known Export-Import Bank.
The Heritage Foundation also created a "Mandate for Leadership" in 2015 ahead of Trump's first term. Two years into his presidency, it touted that Trump had instituted 64% of its policy recommendations, ranging from leaving the Paris Climate Accords, increasing military spending, and increasing off-shore drilling and developing federal lands. In July 2020, the Heritage Foundation gave its updated version of the book to then-White House Chief of Staff Mark Meadows.
The authors of many chapters are familiar names from the Trump administration, such as Russ Vought, who led the Office of Management and Budget; former acting Defense Secretary Chris Miller; and Roger Severino, who was director of the Office of Civil Rights at the Department of Health and Human Services.
Vought is the policy director for the 2024 Republican National Committee's platform committee, which released its proposed platform on Monday.
John McEntee, former director of the White House Presidential Personnel Office under Trump, is a senior advisor to the Heritage Foundation, and said that the group will "integrate a lot of our work" with the Trump campaign when the official transition efforts are announced in the next few months.
Candidates interested in applying for the Heritage Foundation's "Presidential Personnel Database" are vetted on a number of political stances, such as whether they agree or disagree with statements like "life has a right to legal protection from conception to natural death," and "the President should be able to advance his/her agenda through the bureaucracy without hindrance from unelected federal officials."
The contributions from ex-Trump administration officials have led its critics to tie Project 2025 to his reelection campaign, though the former president has attempted to distance himself from the initiative.
Some of the policies in the Project 2025 agenda have been discussed by Republicans for years or pushed by Trump himself: less federal intervention in education and more support for school choice; work requirements for able-bodied, childless adults on food stamps; and a secure border with increased enforcement of immigration laws, mass deportations and construction of a border wall.
But others have come under scrutiny in part because of the current political landscape.
Abortion and social issues
In recommendations for the Department of Health and Human Services, the agenda calls for the Food and Drug Administration to reverse its 24-year-old approval of the widely used abortion pill mifepristone. Other proposed actions targeting medication abortion include reinstating more stringent rules for mifepristone's use, which would permit it to be taken up to seven weeks into a pregnancy, instead of the current 10 weeks, and requiring it to be dispensed in-person instead of through the mail.
The Alliance Defending Freedom, a conservative legal group that is on the Project 2025 advisory board, was involved in a legal challenge to mifepristone's 2000 approval and more recent actions from the FDA that made it easier to obtain. But the Supreme Court rejected the case brought by a group of anti-abortion rights doctors and medical associations on procedural grounds.
The policy book also recommends the Justice Department enforce the Comstock Act against providers and distributors of abortion pills. That 1873 law prohibits drugs, medicines or instruments used in abortions from being sent through the mail.
Now that the Supreme Court has overturned Roe v. Wade , the volume states that the Justice Department "in the next conservative administration should therefore announce its intent to enforce federal law against providers and distributors of such pills."
The guide recommends the next secretary of Health and Human Services get rid of the Reproductive Healthcare Access Task Force established by the Biden administration before Roe's reversal and create a "pro-life task force to ensure that all of the department's divisions seek to use their authority to promote the life and health of women and their unborn children."
In a section titled "The Family Agenda," the proposal recommends the Health and Human Services chief "proudly state that men and women are biological realities," and that "married men and women are the ideal, natural family structure because all children have a right to be raised by the men and women who conceived them."
Further, a program within the Health and Human Services Department should "maintain a biblically based, social science-reinforced definition of marriage and family."
During his first four years in office, Trump banned transgender people from serving in the military. Mr. Biden reversed that policy , but the Project 2025 policy book calls for the ban to be reinstated.
Targeting federal agencies, employees and policies
The agenda takes aim at longstanding federal agencies, like the National Oceanic and Atmospheric Administration, or NOAA. The agency is a component of the Commerce Department and the policy guide calls for it to be downsized.
NOAA's six offices, including the National Weather Service and National Marine Fisheries Service, "form a colossal operation that has become one of the main drivers of the climate change alarm industry and, as such, is harmful to future U.S. prosperity," the guide states.
The Department of Homeland Security, established in 2002, should be dismantled and its agencies either combined with others, or moved under the purview of other departments altogether, the policy book states. For example, immigration-related entities from the Departments of Homeland Security, Justice and Health and Human Services should form a standalone, Cabinet-level border and immigration agency staffed by more than 100,000 employees, according to the agenda.
If the policy recommendations are implemented, another federal agency that could come under the knife by the next administration, with action from Congress, is the Consumer Financial Protection Bureau.
The agenda seeks to bring a push by conservatives to target diversity, equity and inclusion, or DEI, initiatives in higher education to the executive branch by wiping away a slew of DEI-related positions, policies and programs and calling for the elimination of funding for partners that promote DEI practices.
It states that U.S. Agency for International Development staff and grantees that "engage in ideological agitation on behalf of the DEI agenda" should be terminated. At the Treasury Department, the guide says the next administration should "treat the participation in any critical race theory or DEI initiative without objecting on constitutional or moral grounds, as per se grounds for termination of employment."
The Project 2025 policy book also takes aim at more innocuous functions of government. It calls for the next presidential administration to eliminate or reform the dietary guidelines that have been published by the Department of Agriculture for more than 40 years, which the authors claim have been "infiltrated" by issues like climate change and sustainability.
Immigration
Trump made immigration a cornerstone of his last two presidential runs and has continued to hammer the issue during his 2024 campaign. Project 2025's agenda not only recommends finishing the wall along the U.S.-Mexico border, but urges the next administration to "take a creative and aggressive approach" to responding to drug cartels at the border. This approach includes using active-duty military personnel and the National Guard to help with arrest operations along the southern border.
A memo from Immigration and Customs Enforcement that prohibits enforcement actions from taking place at "sensitive" places like schools, playgrounds and churches should be rolled back, the policy guide states.
When the Homeland Security secretary determines there is an "actual or anticipated mass migration of aliens" that presents "urgent circumstances" warranting a federal response, the agenda says the secretary can make rules and regulations, including through their expulsion, for as long as necessary. These rules, the guide states, aren't subject to the Administration Procedure Act, which governs the agency rule-making process.
In a post to his social media platform on July 5, Trump wrote , "I know nothing about Project 2025. I have no idea who is behind it. I disagree with some of the things they're saying and some of the things they're saying are absolutely ridiculous and abysmal. Anything they do, I wish them luck, but I have nothing to do with them."
Trump's pushback to the initiative came after Heritage Foundation President Kevin Roberts said in a podcast interview that the nation is "in the process of the second American Revolution, which will remain bloodless if the left allows it to be."
The former president continued to disavow the initiative this week, writing in another social media post that he knows nothing about Project 2025.
"I have not seen it, have no idea who is in charge of it, and, unlike our very well received Republican Platform, had nothing to do with it," Trump wrote. "The Radical Left Democrats are having a field day, however, trying to hook me into whatever policies are stated or said. It is pure disinformation on their part. By now, after all of these years, everyone knows where I stand on EVERYTHING!"
While the former president said he doesn't know who is in charge of the initiative, the project's director, Dans, and associate director, Chretien, were high-ranking officials in his administration. Additionally, Ben Carson, former secretary of Housing and Urban Development under Trump; John Ratcliffe, former director of National Intelligence in the Trump administration; and Peter Navarro, who served as a top trade adviser to Trump in the White House, are listed as either authors or contributors to the policy agenda.
Still, even before Roberts' comments during "The War Room" podcast — typically hosted by conservative commentator Steve Bannon, who reported to federal prison to begin serving a four-month sentence last week — Trump's top campaign advisers have stressed that Project 2025 has no official ties to his reelection bid.
Susie Wiles and Chris LaCivita, senior advisers to the Trump campaign, said in a November statement that 2024 policy announcements will be made by Trump or his campaign team.
"Any personnel lists, policy agendas, or government plans published anywhere are merely suggestions," they said.
While the efforts by outside organizations are "appreciated," Wiles and LaCivita said, "none of these groups or individuals speak for President Trump or his campaign."
In response to Trump's post last week, Project 2025 reiterated that it was separate from the Trump campaign.
"As we've been saying for more than two years now, Project 2025 does not speak for any candidate or campaign. We are a coalition of more than 110 conservative groups advocating policy & personnel recommendations for the next conservative president. But it is ultimately up to that president, who we believe will be President Trump, to decide which recommendations to implement," a statement on the project's X account said.
The initiative has also pushed back on Democrats' claims about its policy proposals and accused them of lying about what the agenda contains.
Despite their attempts to keep some distance from Project 2025, Democrats continue to connect Trump with the transition effort. The Biden-Harris campaign frequently posts about the project on X, tying it to a second Trump term.
Mr. Biden himself accused his Republican opponent of lying about his connections to the Project 2025 agenda, saying in a statement that the agenda was written for Trump and "should scare every single American." He claimed on his campaign social media account Wednesday that Project 2025 "will destroy America."
Congressional Democrats have also begun pivoting to Project 2025 when asked in interviews about Mr. Biden's fitness for a second term following his lackluster showing at the June 27 debate, the first in which he went head-to-head with Trump.
"Trump is all about Project 2025," Pennsylvania Sen. John Fetterman told CNN on Monday. "I mean, that's what we really should be voting on right now. It's like, do we want the kind of president that is all about Project '25?"
Rep. Jim Clyburn of South Carolina, one of Mr. Biden's closest allies on Capitol Hill, told reporters Monday that the agenda for the next Republican president was the sole topic he would talk about.
"Project 2025, that's my only concern," he said. "I don't want you or my granddaughter to live under that government."
In a statement reiterating her support for Mr. Biden, Rep. Frederica Wilson of Florida called Project 2025 "MAGA Republicans' draconian 920-page plan to end U.S. democracy, give handouts to the wealthy and strip Americans of their freedoms."
Two GOP senators under consideration to serve as Trump's running mate sought to put space between the White House hopeful and Project 2025, casting it as merely the product of a think tank that puts forth ideas.
"It's the work of a think tank, of a center-right think tank, and that's what think tanks do," Florida Sen. Marco Rubio told CNN's "State of the Union" on Sunday.
He said Trump's message to voters focuses on "restoring common sense, working-class values, and making our decisions on the basis of that."
Ohio Sen. J.D. Vance raised a similar sentiment in an interview with NBC's "Meet the Press," saying organizations will have good ideas and bad ideas.
"It's a 900-page document," he said Sunday. "I guarantee there are things that Trump likes and dislikes about that 900-page document. But he is the person who will determine the agenda of the next administration."
Jaala Brown contributed to this report.
Melissa Quinn is a politics reporter for CBSNews.com. She has written for outlets including the Washington Examiner, Daily Signal and Alexandria Times. Melissa covers U.S. politics, with a focus on the Supreme Court and federal courts.
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Here is what to know about Project 2025: What is Project 2025? Project 2025 is a proposed presidential transition project that is composed of four pillars: a policy guide for the next presidential ...