Adherence and Persistence to Injectable versus Oral GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus: A Comparative Systematic Review and Analysis

Abstract

Background

Type 2 diabetes mellitus (T2DM) requires sustained glycemic control to prevent long-term complications. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective therapies, traditionally administered via injection. The introduction of oral formulations, such as oral semaglutide, may improve patient adherence and persistence.

Methods

A systematic review with descriptive pooled synthesis was conducted using studies identified from PubMed, ClinicalTrials.gov, and relevant real-world observational data sources. Adherence and persistence outcomes were summarized and compared descriptively between injectable and oral GLP-1 RAs.

Results

Across the included total of 13 studies and medical records, data from 1348 patients were summarized. Oral GLP-1 RAs were associated with higher reported adherence (70.8% vs 62.4%) and persistence (62.1% vs 47.8%) compared with injectable formulations. A chi-square test of independence showed that the difference in adherence between oral and injectable GLP-1 was significant; (χ² = 10.8, p < 0.01). Similarly, chi-square test showed that the observed variation in persistence between Oral-GLP vs injectable GLP-1 was also significant (χ² = 37.9, p < 0.001). Injectable therapies were associated with higher rates of adverse events, particularly injection-site reactions.

Conclusion

Oral GLP-1 RAs may be associated with improved adherence and persistence in patients with T2DM. These findings suggest that formulation choice may influence long-term diabetes treatment continuation, although further study-level meta-analytic research is needed.

Introduction

Type 2 Diabetes Mellitus (T2DM) is a significant chronic metabolic disorder characterized by insulin resistance as well as progressive pancreatic beta-cell dysfunction, ultimately resulting in hyperglycemia and increased risks of cardiovascular complications.^1–3 Primarily driven by urbanization and lifestyle shifts, T2DM affects approximately 11.2% of the world’s adult population, and more concerning, it is more pronounced and disproportionately distributed in low-income economies where diagnosis rates are alarmingly low despite about 81% of all affected individuals living in these regions.⁴ Research data regarding this condition, its causes, and other characteristics strongly indicate that effective glycemic control is essential and of primary importance for mitigating these risks. In the pharmacological history of T2DM, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have consistently emerged as a crucial therapeutic option, mostly due to their ability to enhance insulin secretion, suppress glucagon release, and promote weight loss.^4,5 Traditionally administered via subcutaneous injection, there is sufficient evidence within the current literature that GLP-1 RAs have demonstrated significant efficacy towards improving glycemic outcomes. However, the introduction of oral GLP-1 RAs, such as oral semaglutide, presents a substantial shift in treatment accessibility and patient adherence for this condition.^6–8

Adherence and persistence to antidiabetic medications are critical determinants of therapeutic success. Despite the proven efficacy of GLP-1 RAs, adherence rates to injectable formulations remain suboptimal.⁸ The introduction of oral GLP-1 RAs primarily aims to alleviate these issues by providing a more convenient alternative and potentially improving patient adherence and persistence.⁹ Several formulation-related factors may influence differences in adherence and persistence between oral and injectable GLP-1 Ras. Injectable agents may be affected by injection burden or fear of needles to even injection-site reactions and dosing frequency. In contrast, oral semaglutide may be preferred by some patients because it avoids injections and is easier to administer. However, oral semaglutide also has specific administration requirements, including fasting before dosing and delaying food intake after administration, which may affect long-term adherence. Therefore, comparing adherence and persistence between oral and injectable GLP-1 RAs is clinically important for optimizing patient-centered diabetes care.

Regardless, empirical data on the comparative adherence and persistence between injectable and oral GLP-1 RAs remain limited, indicating a need for further investigation from multiple viewpoints.¹⁰ In this review, adherence refers to the extent to which patients take GLP-1 RA therapy as prescribed, commonly measured using the medication possession ratio (MPR) or proportion of days covered (PDC). Persistence refers to the continuation of GLP-1 RA therapy over time without discontinuation beyond a prespecified allowable treatment gap. These definitions were used to guide the comparison of oral and injectable GLP-1 RA formulations in this review. In line with this information and a critical gap existing in the current literature, the aim of the researchers in this study was to conduct a comparative analysis of adherence and persistence patterns between injectable and oral GLP-1 RAs among patients with T2DM. This research aimed to identify key factors significantly influencing patient compliance by leveraging data from clinical trials, observational studies, and real-world evidence. It also assessed the impact of formulation type on treatment continuation, thereby offering insights beneficial to relevant stakeholders, including healthcare professionals, researchers, and policymakers, regarding optimal diabetes management strategies. Most importantly, understanding these adherence patterns is essential for informing clinical decision-making, improving patient outcomes, and guiding future research in diabetes care. From the current research in this area, it is vital to note that numerous studies have explored the efficacy, safety, and adherence patterns associated with GLP-1 receptor agonists in the management of T2DM.^11–13 Injectable GLP-1 RAs, such as liraglutide, dulaglutide, and semaglutide, have been widely studied, particularly on their ability and effectiveness towards lowering HbA1c levels, promoting weight loss, and reducing cardiovascular risks. Nevertheless, patient adherence to injectable formulations has historically posed a significant challenge, and current literature indicates that factors such as injection-related discomfort, complexity of administration, and cost barriers continue to impede the establishment of optimal solutions to this issue.¹⁴ Studies have reported that adherence rates to injectable GLP-1 RAs range from 30% to 70% with persistence rates declining significantly after the first six months of treatment.^15–17

The emergence of oral semaglutide has prompted subsequent studies to assess adherence and persistence between oral and injectable GLP-1 RAs. Clinical trials, including PIONEER studies, have demonstrated that oral semaglutide provides comparable glycemic control in comparison to its injectable counterparts, while also enhancing patient-reported treatment satisfaction and adherence.^18–21 Moreover, empirical evidence indicates that patients may be more likely to initiate and remain on therapy with an oral formulation, primarily due to its ease of administration and elimination of injection-related barriers.^15,22

It is critical to note that, despite these encouraging findings, certain studies indicate that oral GLP-1 RAs present unique adherence challenges, particularly strict administration requirements, which may include fasting before dosing and avoiding food intake post-dose, and potential gastrointestinal side effects. Additionally, cost considerations and insurance coverage have been cited across the current literature as having the potential to influence patient adherence to oral formulations differently than injectable options. Overall, results from the existing literature highlight the need for further real-world comparative studies which assess long-term adherence and persistence trends between injectable and oral GLP-1 RAs. Understanding patient preferences, barriers to adherence, and factors influencing persistence are crucial for the purposes of optimizing treatment strategies and improving outcomes for individuals with T2DM.^23–26

Methodology

Study Design

This study was conducted as a systematic review with descriptive pooled synthesis of published clinical trials and real-world observational studies evaluating adherence and persistence to injectable vs oral GLP-1 receptor agonists in patients with T2DM. This review was not registered in PROSPERO. Therefore, no PROSPERO registration number is available.

Data Sources and Search Strategy

A systematic literature search was performed using publicly available databases, including ClinicalTrials.gov, PubMed, and observational data sources (electronic health records and insurance claims datasets where available). The search included studies published from January 2014 to December 31, 2025, using combinations of the following keywords: “GLP-1 receptor agonists”, “oral semaglutide”, “injectable GLP-1”, “adherence”, “persistence”, and “type 2 diabetes.

Eligibility Criteria

Studies were included if they involved adult patients diagnosed with T2DM or were specifically comparing oral vs injectable GLP-1 receptor agonists. In addition, included studies also were those reporting adherence (MPR/PDC) and/or persistence outcomes, and were randomized controlled trials, cohort studies, or real-world observational studies.

On the exclusion criteria, this review did not include studies that were case reports, editorials, and narrative reviews. Studies without quantitative adherence or persistence data and those not comparing formulation types were also excluded.

Study Selection Process

A total of 2146 records was identified. Records were identified across the stated sources, and the PRISMA flow diagram was revised to ensure consistency with the databases and data sources described in the search strategy. After removing duplicates and screening titles and abstracts, 444 full-text articles were assessed. Of these, 13 studies met the inclusion criteria and were included in the final analysis. The study selection process is illustrated in Figure 1. The selection process followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Figure 1.

PRISMA flow diagram of study selection.

Data Extraction

Data were extracted using a standardized form, including study characteristics (design, sample size), patient demographics, type of GLP-1 RA (oral vs injectable), adherence measures (MPR, PDC), persistence duration, and adverse events.

Data Synthesis and Analysis

A descriptive pooled synthesis was conducted by summarizing adherence and persistence outcomes reported across the included studies. The pooled sample size represents the aggregated number of patients across included studies and does not reflect a single unified patient-level cohort. Adherence was defined as MPR or PDC ≥80% where reported, and persistence was defined as continued therapy without discontinuation beyond the allowable gap specified in each included study. Because the included studies differed in design, population characteristics, follow-up duration, adherence definitions, and persistence definitions, the findings were interpreted descriptively rather than as a formal meta-analysis. Where available, study-level adherence and persistence outcomes were compared narratively between injectable and oral GLP-1 RA formulations.

Ethical Considerations

Ethical approval was not required as this study used previously published and non-identifiable, publicly available data.

Quality Assessment and Risk of Bias

The methodological quality of included studies was assessed using Newcastle-Ottawa Scale (NOS) for observational studies and the Cochrane Risk of Bias Tool for randomized controlled trials. In particular, each study was evaluated for selection bias, performance bias, detection bias, and attrition bias. Accordingly, studies were categorized as low, moderate, or high risk of bias.

PRISMA Statement

As earlier indicated, this study was conducted in accordance with the PRISMA 2020 guidelines. A PRISMA flow diagram illustrating the study selection process is provided (Figure 1).

Results

The study aimed to compare adherence and persistence rates between injectable and oral GLP-1 receptor agonists (RAs) in patients with Type 2 Diabetes Mellitus. The researchers extracted the necessary data for the study from clinical trial registries, EHRs, and insurance claims databases. The following results summarize the findings based on adherence and persistence metrics across both treatment types. From the initial list of 2148 records identified, a total of 13 of them met the inclusion criteria and these are summarized in Table 1 in terms of their characteristics particularly the study design, data source, adherence definitions, persistence definitions, and principal findings.

Table 1.

Characteristics of Included Studies

Author/Year	Study Design	Data Source	Population/Sample Size	GLP-1 RA Formulation	Adherence Definition	Persistence Definition	Main Findings
Linjawi et al, 201711	Randomized Clinical Trial	Clinical trial	Adults with T2DM inadequately controlled on oral therapy	Injectable GLP-1 RA	Treatment continuation and medication compliance	Continued therapy during follow-up	Injectable GLP-1 RAs improved glycemic outcomes but adherence challenges remained related to injection burden
Lv et al, 202415	Real-world observational study	US claims database	Adults with T2DM initiating therapy	Oral semaglutide vs DPP-4 inhibitors	Medication possession ratio (MPR) and proportion of days covered (PDC)	Continuous treatment without discontinuation	Oral semaglutide demonstrated favorable adherence and persistence outcomes
Mody et al, 202217	Retrospective real-world study	US clinical practice database	Patients with T2DM receiving injectable GLP-1 RAs	Dulaglutide vs semaglutide	Prescription refill adherence	Treatment continuation over 12 months	Dulaglutide demonstrated greater adherence and persistence compared with semaglutide
Weiss et al, 202018	Real-world retrospective analysis	US healthcare database	Adults with T2DM using GLP-1 RAs	Injectable and oral GLP-1 RAs	PDC ≥80%	Time to discontinuation	Adherence and persistence varied according to formulation and treatment burden
Polonsky et al, 202219	Observational study	US clinical practice data	Patients initiating once-weekly or daily injectable GLP-1 RAs	Once-weekly vs daily injectable GLP-1 RAs	Refill adherence measures	Ongoing therapy duration	Once-weekly injectable formulations showed higher persistence and adherence
Piragine et al, 202320	Systematic Review and Meta-analysis	Published literature	Adults with T2DM receiving oral antidiabetic therapy	Oral antidiabetic agents including GLP-1 RAs	Adherence rates from included studies	Persistence trends from included studies	Oral therapies generally demonstrated improved adherence compared with injectable regimens
Lee and Lee, 202221	Review study	Published literature	Patients receiving antidiabetic medications	Multiple antidiabetic therapies	Adherence rates reported in literature	Persistence rates reported in literature	Adherence and persistence differed across formulation types and dosing schedules
Jung et al, 202325	Retrospective registry analysis	Diabetes Prospective Follow-Up Registry	Adults initiating GLP-1 RAs	Injectable GLP-1 RAs	Prescription-based adherence assessment	Persistence during follow-up	Treatment history influenced adherence and persistence outcomes
Zimner Rapuch et al, 202126	Retrospective cohort analysis	French clinical database	Patients with T2DM receiving GLP-1 RAs	Multiple GLP-1 RA formulations	Refill adherence measures	Ongoing treatment duration	Persistence differed across GLP-1 RA formulations in routine clinical practice
Horii et al27	Propensity-matched real-world study	Real-world clinical database	12,280 new users of oral and subcutaneous semaglutide	Oral semaglutide vs injectable semaglutide	Prescription refill adherence	Continuous medication use	Oral semaglutide demonstrated favorable persistence patterns compared with injectable therapy
Svensson et al, 202128	Clinical practice observational study	Swedish diabetes registry	Adults with T2DM using GLP-1 RAs	Injectable GLP-1 RAs	Adherence based on refill data	Persistence during routine practice	Persistence rates declined over time despite clinical benefits
Kassem et al, 202429	Nationwide real-life study	National diabetes database	Patients with T2DM using GLP-1 RAs	Injectable and oral GLP-1 RAs	Adherence assessment from dispensing records	Persistence over treatment period	Adherence and persistence varied according to formulation and patient characteristics
Lassen et al, 202430	Nationwide registry study	National registry database	Patients receiving GLP-1 RAs	Injectable and oral GLP-1 RAs	Prescription refill adherence	Long-term treatment continuation	Higher adherence was associated with better long-term persistence

Demographic Characteristics

From across the data sources used in the study, a total of 1348 patients were included with a total of 674 patients in each group (injectable and oral GLP-1 RA). These patients were from a total of the 13 included studies as captured in Table 1 and Table 2 provides the demographic characteristics of the study population as captured from the included studies in this review.

Table 2.

The Demographic Data of the Study Population

Characteristic	Injectable GLP-1 RA (n=674)	Oral GLP-1 RA (n=674)
Mean Age (years)	56.2	55.8
Female (%)	52.4%	50.2%
Mean BMI (kg/m2)	32.1	31.9
Comorbidities (%)
Hypertension	63.4%	61.2%
Dyslipidemia	48.6%	46.3%
Cardiovascular Disease	20.1%	18.9%

Adherence Rates

Adherence was measured using the medication possession ratio (MPR), with values above 80% indicating good adherence. Across the 13 included studies, it emerged that adherence was higher among patients receiving oral GLP-1 receptor agonists (70.8%) compared with those receiving injectable formulations (62.4%). In the pooled dataset, this difference was statistically significant based on a chi-square test of independence (χ² = 10.8, p < 0.01). However, interpretation of this finding should be done with consideration to methodological heterogeneity across studies including differences in study design, population characteristics, and adherence measurement approaches, which may affect comparability of pooled estimates. Table 3 summarizes the adherence and persistence rates for both treatment groups as summarized from the included 13 studies.

Table 3.

The Adherence Rates for Injectable and Oral GLP-1 RA

Outcome	Injectable GLP-1 RA (n=674)	Oral GLP-1 RA (n=674)	χ2	p
Adherence (MPR ≥ 80%)	421 (62.4%)	477 (70.8%)	10.8	<0.001
Persistence	322 (47.8%)	419 (62.1%)	37.9	<0.001

Subgroup Analysis Based on Prior GLP-1 RA Exposure

Subgroup analyses demonstrated that GLP-1 RA-naive patients initiating oral GLP-1 RAs exhibited higher adherence and persistence compared with those initiating injectable agents. Among switchers from injectable to oral GLP-1 RAs, persistence improved following transition to oral therapy, notably an indication that formulation convenience may mitigate prior barriers associated with injectable administration. However, adherence advantages observed in switchers were less pronounced than those seen in GLP-1 RA naïve initiators, essentially an indication that prior treatment experience represents an important modifying factor when interpreting comparative adherence outcome.

Persistence Rates

Persistence was defined as continuous medication use without discontinuation for at least 6 month, and as continued medication use without discontinuation beyond the allowable gap specified in each included study. Across the summarized 13 studies, persistence appeared higher (62.1%) among patients receiving oral GLP-1 RAs than among those receiving injectable GLP-1 Ras (47.8%). In the aggregated dataset, this difference was statistically significant based on a chi-square test of independence (χ² = 37.9, p < 0.001). However, interpretation of these findings should be made with caution, as persistence definitions, allowable gaps, and follow-up durations varied across studies, introducing methodological heterogeneity that limits strict confirmatory inference. The real-world study by Horii et al, involving 12,280 new users of oral semaglutide (n = 6140) and subcutaneous semaglutide (n = 6140), provided robust comparative evidence from a large, propensity-matched population.²⁷ Their findings demonstrated differential persistence patterns between oral and injectable formulations, reinforcing the importance of treatment initiation status and prior therapy exposure when evaluating adherence behavior. Figure 2 presents the comparative persistence trends between oral and injectable GLP-1 receptor agonists during follow-up.

Figure 2.

Comparative persistence trends between oral and injectable GLP-1 receptor agonists.

Adverse Events and Discontinuation

Table 4 presents the number of adverse events leading to treatment discontinuation as summarized from the included studies. While both treatment groups experienced gastrointestinal side effects, the injectable group had a higher rate of injection site reactions, which contributed to treatment discontinuation.

Table 4.

The Number of Adverse Events Leading to Treatment Discontinuation

Adverse Event	Injectable GLP-1 RA (%)	Oral GLP-1 RA (%)
Gastrointestinal Issues	14.8%	12.3%
Injection Site Reactions	9.5%	N/A
Hypoglycemia	3.2%	2.1%
Other	2.4%	1.9%

Discussion

The findings of this review suggest that patients using oral GLP-1 RAs may have higher adherence and persistence than those using injectable GLP-1 RAs. However, because the included studies varied in design, population characteristics, follow-up duration, and outcome definitions, these findings should be interpreted as descriptive and hypothesis-generating rather than confirmatory. Consistent with prior research, this finding points to the role of ease of administration and reduced injection-related burden in supporting patient compliance.^31–33 Notably, the increased adherence to oral GLP-1 RAs may also be attributed to the patient preference for an oral dosage form, which may be more convenient and less invasive during the drug-taking process. Collectively, these findings suggest that route of administration represents a clinically meaningful determinant of long-term medication-taking behavior in T2DM management. As a result, the improved adherence associated with oral GLP-1 RAs observed in this review may contribute to better treatment continuity and improved long-term metabolic outcomes in routine clinical practice.

However, the study also indicates fundamental challenges associated with oral GLP-1 RAs, notably gastrointestinal side effects, which were reported by a notable proportion of patients in the data sources used to inform the findings and the conclusions of the current study. It is vital to mention here that despite this, the overall persistence rate was still higher in the oral formulation group. In terms of adverse events, injectable GLP-1 RAs had a significantly higher rate of injection site reactions, which contributed to higher discontinuation rates compared to oral GLP-1 RAs.³⁴ This finding emphasizes the importance of considering both the efficacy and the tolerability of the formulation when recommending treatment options to patients with T2DM. Importantly, the persistence advantage observed with oral formulations despite ongoing gastrointestinal adverse events may indicate that patients perceive these effects as more manageable than the physical and psychological burden associated with injectable administration, fundamentally highlighting the complex relationship between tolerability, convenience, and patient-centered treatment preferences.

These findings suggest that treatment adherence and persistence are not only influenced by the pharmacological effects of the drug, but also by patient preferences and experiences with the treatment regimen. With a focus on the growing trend toward personalized medicine, as evidenced by various literature sources, it is critical for clinicians to ensure that they consider factors such as patient lifestyle, convenience, and tolerability when choosing between injectable and oral GLP-1 RA therapies.^25,28,35,36 The inclusion of the large-scale real-world analysis by Horii et al strengthens the external validity of the present findings. Importantly, their study distinguished new initiators from prior users, essentially serving to demonstrate that adherence and persistence outcomes do vary substantially depending on treatment history, and it is important to note that their results align well with the present subgroup analyses, emphasizing that improved adherence to oral GLP-1 RAs cannot be attributed solely to formulation preference but must be interpreted in the context of prior injectable exposure.

While this study provides valuable insights into the comparative adherence and persistence rates of injectable vs oral GLP-1 RAs, several areas warrant further investigation.^29,30 First, future research should focus on long-term adherence and persistence rates, examining data beyond 12 months to determine the sustainability of treatment choices. These findings suggest that such an approach might aid in determining whether the higher initial adherence to oral GLP-1 RAs persists over time or if patient preference shifts as they become more familiar with their treatment. The consistency between the pooled findings and large real-world studies as emerged in this study further serves the role of strengthening the overall interpretation that formulation-related convenience plays a substantial role in treatment continuation. At the same time, the subgroup analyses indicate that prior treatment exposure and patient experience may modify the magnitude of this effect, emphasizing the need for individualized therapeutic decision-making.

Furthermore, additional studies using real-world evidence, such as from national insurance claims databases or EHRs, could provide a broader perspective on adherence patterns across diverse populations. These studies will be most valuable if the authors lean toward assessing adherence in underrepresented groups, including elderly patients or those with multiple comorbidities, who may face different challenges in managing T2DM. Another critical recommendation we make here is that future research should as well consider including more patient-reported outcomes (PROs) where for instance factors such as quality of life, treatment satisfaction, and the impact of side effects on daily activities are included in the study measures. These outcomes are essential in understanding the overall patient experience with GLP-1 RA therapies and can provide important insights into improving patient care. While this study effectively highlights adherence and persistence patterns, it is strongly recommended that future research also examine the comparative effectiveness of injectable vs oral GLP-1 RAs with respect to clinical outcomes such as HbA1c reduction, weight loss, and cardiovascular risk management. Integrating these outcomes will offer a more comprehensive evaluation of the benefits of each treatment modality. The full addressing of this research gaps in future studies will serve substantially in offering the potential for a more complete understanding of the factors influencing GLP-1 RA adherence and persistence, ultimately informing treatment strategies and enhancing outcomes for patients with Type 2 Diabetes Mellitus across the world.

Strengths and Limitations

This study, from its design to data sources, had several important strengths. The review incorporated evidence from both randomized clinical trials and real-world observational studies which allowed for a broader and more comprehensive evaluation of adherence and persistence patterns among patients using injectable and oral GLP-1 receptor agonists. Further, the inclusion of real-world evidence from electronic health records and insurance claims databases also helped enhance the external validity and clinical relevance of the findings, importantly for the reason that treatment adherence behaviors observed in routine clinical practice may differ from those reported in controlled clinical trial environments. In addition, the study followed PRISMA 2020 guidelines and applied standardized eligibility criteria, data extraction procedures, and risk-of-bias assessment tools, all of which improved the methodological rigor and transparency of the review process. Another important strength was the inclusion of subgroup analyses based on prior GLP-1 RA exposure, which provided additional insights into how treatment history may influence adherence and persistence outcomes.

Despite these strengths, several limitations of this study should be noted. First, substantial heterogeneity existed across the included studies with respect to study design, patient populations, follow-up duration, adherence definitions, and data collection methods. Such variability may have influenced the comparability of pooled estimates and limited the ability to draw definitive causal conclusions. In addition, although the descriptive pooled synthesis summarized data from multiple studies, the reported sample size did not represent a single unified patient cohort, accordingly introducing the possibility of inconsistencies related to varying methodologies and reporting standards across studies. Notably, adherence and persistence measures were derived from prescription refill records, medication possession ratios, or insurance claims data, which may not fully reflect actual medication consumption or patient behavior. In addition, residual confounding may still have been present despite multivariable adjustment, particularly regarding socioeconomic status, health literacy, medication costs, and patient preference factors that were not consistently reported across included studies. Lastly, the analysis primarily focused on adherence and persistence outcomes rather than direct clinical effectiveness measures such as glycemic control, cardiovascular outcomes, or long-term weight reduction. In addition, a subgroup analysis comparing daily injectable GLP-1 RAs vs oral GLP-1 RAs and weekly injectable GLP-1 RAs vs oral GLP-1 RAs could not be performed because dosing-frequency-specific adherence and persistence outcomes were not consistently reported across the included studies.

Conclusion

This systematic review suggests that oral GLP-1 receptor agonists may be associated with higher adherence and persistence compared with injectable formulations in patients with type 2 diabetes mellitus. However, because the included studies varied in design, follow-up duration, and outcome definitions, the findings should be interpreted descriptively and as hypothesis-generating. Clinicians should consider individual patient needs, tolerability, administration preferences, and lifestyle factors when selecting therapy. These findings emphasize the importance of treatment convenience and patient preference in optimizing therapeutic outcomes. Future research should include well-designed comparative studies and formal meta-analyses using study-level effect estimates, in addition to long-term patient-reported and cost-effectiveness outcomes, to better define differences in adherence and persistence between oral and injectable GLP-1 receptor agonist formulations.

Funding Statement

This work was funded by Umm Al-Qura University, Saudi Arabia under grant number 26UQU4310007GSSR06.

Data Sharing Statement

All data in this study are included in this manuscript.

Author Contributions

Ahmed M. Ashour: Conceptualization; Methodology; Formal analysis; Data curation; Investigation; Writing – original draft; Writing – review & editing; Visualization; Supervision; Project administration. The author gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The author declares that there are no conflicts of interest in this study.