GLP-1 receptor agonists for weight loss: A systematic review and meta-analysis of randomized controlled trials

Abstract

Background:

Obesity is a complex condition marked by excessive body fat, linked to comorbidities such as type 2 diabetes and cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor agonists, initially developed for diabetes, are increasingly used for weight management.

Methods:

We conducted a systematic review and meta-analysis of randomized controlled trials (PubMed, last 5 years, English language) evaluating GLP-1–based pharmacotherapies versus placebo or active comparators for weight loss. The primary endpoint was the proportion of participants achieving any weight loss during follow-up. Pooled odds ratios were estimated using a fixed-effect model with 95% confidence intervals; heterogeneity was quantified with I². A frequentist network meta-analysis generated SUCRA rankings. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. No protocol was registered.

Results:

Twenty-one trials met the inclusion criteria (n = 7024 in pairwise analyses). Across 16 placebo-controlled trials, a higher proportion of participants achieved weight loss with GLP- 1–based agents than with placebo: 78.54% (3231/4114) versus 26.53% (772/2910); pooled odds ratio: 11.37 (95% confidence interval: 8.10–15.98), P < .0001; I² = 82%. In the network meta-analysis, tirzepatide and semaglutide ranked highest (surface under the cumulative ranking curve 91.2% and 85.4%, respectively).

Conclusion:

GLP-1 receptor agonists significantly increase the likelihood of weight loss versus placebo, with tirzepatide and semaglutide demonstrating the greatest relative efficacy among agents evaluated. These findings support GLP-1–based therapy as an effective component of clinical obesity management.

1. Introduction

The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with extensive therapeutic applications. GLP-1 has several metabolic effects, including glucose-dependent stimulation of insulin secretion, decreased stomach emptying, suppression of food intake, increased natriuresis and diuresis, and control of rodent β-cell proliferation. GLP-1 also has cardio- and neuroprotective properties, reduces inflammation and apoptosis, and influences learning and memory, reward behavior, and palatability.^[1] GLP-1 receptor agonists (GLP-1 RAs), which have been biochemically modified for increased potency and prolonged effect, are successfully used in clinical trials to treat type 2 diabetes (T2D), and many GLP-1-based pharmacotherapies are also being studied for the treatment of obesity.^[1]

GLP-1 agonists are a family of drugs used to treat T2D and obesity.^[2] GLP-1 RAs are appealing choices for the treatment of T2D because they successfully decrease hemoglobin A1c and weight while posing a low risk of hypoglycemia. Some GLP-1 RAs have also been linked to cardiovascular benefits.^[3] Müller et al reported that GLP-1 RAs are effectively used in clinical trials to treat T2D, and numerous GLP-1-based pharmacotherapies are being tested for the treatment of obesity.^[1]

Obesity is a complex, multifactorial condition in which accumulated extra body fat has a detrimental impact on health. Obesity continues to rise, culminating in an extraordinary epidemic that shows no indications of slowing down anytime soon.^[4] Raised body mass index (BMI) is a risk factor for noncommunicable illnesses such as diabetes, cardiovascular disease (CVD), and musculoskeletal problems, which result in a significant loss in life quality and expectancy.^[4] The World Health Organization defines overweight and obesity as abnormal or excessive fat accumulation that poses a health risk.^[5] Overweight is defined as a BMI of 25 kg/m² or above, whereas obesity is defined as a BMI of 30 kg/m². Obesity and overweight are widely known to be global concerns, with a high incidence in both developed and developing nations.^[5–7]

Obese patients are at high risk of developing a variety of comorbid conditions, such as CVD, gastrointestinal disorders, T2D, joint and muscular disorders, respiratory problems, and psychological issues, all of which can have a significant impact on their daily lives while also increasing their mortality risk.^[8] Obesity can lead to a variety of illnesses, including CVD, diabetes, obstructive sleep apnea, and hypertension.^[8] Fruh stated that a very moderate and uncomplicated weight loss, such as 5%, can enhance patient outcomes and serve as a catalyst for future change, with long-term weight loss achieved by a series of incremental weight loss stages.^[9]

Obesity has become one of the world’s most serious public health concerns, highlighting the need for evidence-based nutritional regimens for weight loss and maintenance.^[10] Evidence-based obesity treatment encompasses therapies in 5 primary categories: behavioral interventions, diet, physical activity, medication, and metabolic/bariatric procedures.^[11] Behavioral interventions can result in weight loss of 5% to 10%, pharmacotherapy treatment with drugs such as GLP-1 agonists and glucose-dependent insulinotropic polypeptide/GLP-1 RAs results in weight loss of 8% to 21%, and bariatric surgery results in weight loss of 25% to 30%. Nonpregnant individuals with obesity or overweight and weight-related comorbidities should be treated with anti-obesity medications in combination with lifestyle changes.^[11] Recent advancements in anti-obesity medications have created the possibility of obtaining clinically substantial weight loss. Increasing data indicate that behavior-based therapies that include one of these drugs can reduce weight more than routine care conditions.^[12]

Aside from lowering blood glucose and weight (particularly visceral fat), GLP-1 agonists can also lower blood pressure, improve blood lipid disorders, and reduce fatty liver.^[13,14] Given the greater weight reduction efficacy and safety of GLP-1 agonists, the Food and Drug Administration has formally authorized several of these medications for chronic weight management of obese or overweight individuals.^[13,14] White et al conducted a retrospective cohort analysis involving approximately 2400 people with overweight or obesity and T2D. They discovered that the majority of patients who started using a GLP-1 agonist lost weight over 72 weeks, with one-third losing a clinically significant amount (at least 5% of body weight). This shows that GLP-1 agonists might be utilized to help people lose weight in real-world situations.^[15]

Popoviciu et al found that GLP-1 agonists, which are used to treat T2D, are helpful in inducing weight reduction in both preclinical and clinical investigations.^[16] There is potential for more study into improving and optimizing the use of GLP-1 in diabetes and nondiabetic obesity in order to minimize morbidity and mortality associated with both metabolic illnesses and improve quality of life. However, certain possible extra effects beyond weight reduction may theoretically contribute to some clinical outcomes, although data from clinical trials are limited. The current meta-analysis sought to investigate the efficacy of GLP-1 agonists for weight loss.

2. Materials and methods

2.1. Study design

The analysis included clinical trials that compared the efficacy of GLP-1 agonists for weight loss that were identified using PubMed. These clinical trials either compared the efficacy of GLP-1 agonists with a placebo or compared the effectiveness of different GLP-1 agonists. The keywords “GLP-1 agonists” and “weight loss” were used in the search.

2.2. Data collection

The analysis included only published human clinical studies and all clinical trials written in English and published during the last 5 years. We excluded other types of studies. The information gathered included the total number of patients who received the medicine in the intervention group, the number of patients who lost weight in the intervention group, the number of patients who received the placebo or drug in the control group, and the number of patients who lost weight in the control group. The occurrence of weight loss in the GLP-1 agonist group was the endpoint of our study. Ethical approval was not required since all data included in this analysis were sourced from existing studies.

2.3. Statistical analysis

We prepared a forest plot for each analysis. We used an odds ratio and a fixed-effect model with 95% confidence intervals (CIs) to compare the groups. The data were displayed by generating a forest plot using odds ratio (OR). The I² statistics were used to assess the study heterogeneity. An I² score of 50% or greater denoted considerable trial heterogeneity. Google Colab was used to find surface under the cumulative ranking curve (SUCRA) rankings and the probability of being best. The statistically significant P value of .05 was chosen. The meta-analyses were conducted using Review Manager software (RevMan, version 5.4; Cochrane Collaboration, London, United Kingdom).

2.4. Ethics

This study synthesized data from previously published clinical trials and did not involve new data collection from human participants. In accordance with the policies of the Research Ethics Committee, Prince Sattam Bin Abdulaziz University (Al-Kharj, Saudi Arabia), formal Institutional Review Board approval was not required for this meta-analysis, and informed consent was not applicable.

3. Results

The current analysis incorporated published clinical studies on GLP-1 agonists for weight loss from PubMed. The keywords “GLP-1 agonists” and “weight loss” yielded 2085 studies. The analysis removed studies that were not clinical trials or were submitted in languages other than English (1885 studies were excluded). We further narrowed the search to include trials conducted during the last 5 years (104 trials were excluded). Following that, the remaining 96 studies were evaluated for eligibility, with 21 trials included in the analysis (Table 1 and Fig. 1).^[17–37]

Table 1.

The included studies.

Study	Year	Medications	Participants
Inagaki et al[17]	2022	Tirzepatide vs dulaglutide	Patients with type 2 diabetes
Lingvay et al[18]	2023	Tirzepatide vs placebo	Patients with type 2 diabetes
Elkind-Hirsch et al[19]	2022	Liraglutide vs placebo	Women with PCOS
Rosenstock et al[20]	2023	Retatrutide vs placebo	Patients with type 2 diabetes
Jensen et al[21]	2023	Liraglutide vs semaglutide	Patients having bariatric surgery
Aroda et al[22]	2019	Semaglutide vs placebo	Patients with type 2 diabetes
Rodbard et al[23]	2019	Semaglutide vs empagliflozin	Patients with type 2 diabetes
Rubino et al[24]	2022	Semaglutide vs liraglutide	Adults with obesity without diabetes
Zhang et al[25]	2024	Mazdutide vs placebo	Patients with type 2 diabetes
Wadden et al[26]	2023	Tirzepatide vs placebo	Adults with obesity without diabetes
Mok et al[27]	2023	Liraglutide vs placebo	Adults with obesity without diabetes
Jastreboff et al[28]	2023	Retatrutide vs placebo	Adults with obesity without diabetes
Silver et al[29]	2023	Liraglutide vs sitagliptin	Adults with obesity and prediabetes
Weghuber et al[30]	2022	Semaglutide vs placebo	Adults with obesity without diabetes
Jastreboff et al[31]	2022	Tirzepatide vs placebo	Adults with obesity without diabetes
Dahl et al[32]	2022	Tirzepatide vs placebo	Adults with type 2 diabetes
Nahra et al[33]	2021	Cotadutide vs placebo	Adults with type 2 diabetes
Rubino et al[34]	2021	Semaglutide vs placebo	Adults with obesity without diabetes
Wadden et al[35]	2021	Semaglutide vs placebo	Adults with obesity without diabetes
Wilding et al[36]	2021	Semaglutide vs placebo	Adults with obesity without diabetes
Ji et al[37]	2021	Semaglutide vs sitagliptin	Adults with type 2 diabetes

PCOS = polycystic ovary syndrome.

Figure 1.

Flowchart of included studies.

Sixteen clinical trials evaluated the rates of weight reduction among participants who took drugs (GLP-1 agonists: semaglutide, tirzepatide, liraglutide, retatrutide, mazdutide, and cotadutide) compared with those who got a placebo (Table 2). Semaglutide trials (6 trials) revealed that 79.90% of patients reduced weight against 30.30% with a placebo. Tirzepatide trials (4 trials) demonstrated that 79.38% of patients decreased weight compared with 24.72% with a placebo. Furthermore, liraglutide trials (2 trials) revealed that 63.16% of individuals decreased weight, compared with 14.04% with placebos. Retatrutide trials (2 trials) revealed that 73.03% of patients decreased weight, compared with 18.63% with a placebo. Furthermore, the mazdutide research found that 77.5% of participants lost weight versus 19.6% with placebo. The cotadutide experiment indicated that 40.0% of participants decreased weight, compared with 9.9% with a placebo. In all cases, people who got the medicine lost much more weight than those who took the placebo. Nine studies evaluated the rates of weight reduction among participants who took different drugs (Table 3). All of the included studies were randomized, and some of the studies had a low risk of bias (Table 4).

Table 2.

The percentage of people who lost weight after taking either GLP-1 agonists or a placebo.

Study	Event	Total	Percentage	Event	Total	Percentage
Zhang et al[25]	Mazdutide			Placebo
	38	49	77.5%	10	51	19.6%
Wadden et al[26]	Tirzepatide			Placebo
	251	287	87.5%	48	282	17.0%
Lingvay et al[18]	Tirzepatide			Placebo
	73	121	60.3%	6	112	5.4%
Mok et al[27]	Liraglutide			Placebo
	23	32	71.9%	3	34	8.8%
Jastreboff et al[28]	Retatrutide			Placebo
	63	68	92.6%	18	68	26.5%
Rosenstock et al[20]	Retatrutide			Placebo
	2	21	9.5%	1	34	2.9%
Elkind-Hirsch et al[19]	Liraglutide			Placebo
	25	44	56.8%	5	23	21.7%
Weghuber et al[30]	Semaglutide			Placebo
	95	131	72.5%	11	62	17.7%
Jastreboff et al[31]	Tirzepatide			Placebo
	536	630	85.1%	225	643	35.0%
Rubino et al[24]	Semaglutide			Placebo
	83	117	70.9%	13	85	15.3%
Dahl et al[32]	Tirzepatide			Placebo
	56	116	48.3%	7	120	5.8%
Nahra et al[33]	Cotadutide			Placebo
	30	75	40.0%	9	91	9.9%
Rubino et al[34]	Semaglutide			Placebo
	475	535	88.8%	128	268	47.8%
Wadden et al[35]	Semaglutide			Placebo
	306	407	75.2%	55	204	27.0%
Wilding et al[36]	Semaglutide			Placebo
	1128	1306	86.4%	206	655	31.4%
Aroda et al[22]	Semaglutide			Placebo
	47	175	26.9%	27	178	15.2%

GLP-1 = glucagon-like peptide-1.

Table 3.

The percentage of people who lost weight after taking different GLP-1 agonists.

Study	Event	Total		Percentage	Event	Total	Percentage
Jensen et al[21]	Semaglutide				Liraglutide
	18	21	85.71		20	29		68.97
Ji et al[37]	Semaglutide				Sitagliptin
	160	290	55.17		17	290		5.86
Lingvay et al[18]	Semaglutide				Tirzepatide
	235	461	50.98		286	461		62.04
Rodbard et al[23]	Semaglutide				Empagliflozin
	164	411	39.90		160	410		39.02
Rubino et al[24]	Semaglutide				Liraglutide
	83	117	70.94		30	117		25.64
Inagaki et al[17]	Dulaglutide				Tirzepatide
	17	159	10.69		97	159		61.01
Rosenstock et al[20]	Dulaglutide				Tirzepatide
	1	40	2.50		2	21		9.52
Zhang et al[25	Dulaglutide				Mazdutide
	18	50	36.00		38	49		77.55
Silver et al[29]	Liraglutide				Sitagliptin
	10	44	22.73		1	22		4.55

GLP-1 = glucagon-like peptide-1.

Table 4.

Risk of bias assessment for all included RCTs.

Study	Randomization	Deviations	Missing data	Outcome measurement	Reporting	Overall
Inagaki et al[17]	Randomized	Low risk	Low risk	Low risk	Low risk	Low risk
Lingvay et al[18]	Randomized	Some concerns	Low risk	Low risk	Low risk	Some concerns
Elkind-Hirsch et al[19]	Randomized	Low risk	Some concerns	Low risk	Low risk	Some concerns
Rosenstock et al[20]	Randomized	Low risk	Low risk	Low risk	Low risk	Low risk
Jensen et al[21]	Randomized	Low risk	23% attrition	Low risk	Low risk	High risk
Aroda et al[22]	Randomized	Low risk	Low risk	Low risk	Low risk	Low risk
Rodbard et al[23]	Randomized	Low risk	17% dropout	Low risk	Low risk	Some concerns
Rubino et al[24]	Randomized	Low risk	Low risk	Low risk	Low risk	Low risk
Zhang et al[25]	Randomized	Low risk	Low risk	Low risk	Low risk	Low risk
Wadden et al[26]	Randomized	Some concerns	Low risk	Low risk	Low risk	Some concerns
Mok et al[27]	Randomized	Low risk	Low risk	Low risk	Low risk	Low risk
Jastreboff et al[28]	Randomized	Low risk	Low risk	Low risk	Low risk	Low risk
Silver et al[29]	Randomized	Low risk	Some concerns	Low risk	Low risk	Some concerns
Weghuber et al[30]	Randomized	Low risk	Low risk	Low risk	Low risk	Low risk
Jastreboff et al[31]	Randomized	Low risk	Low risk	Low risk	Low risk	Low risk
Dahl et al[32]	Randomized	Low risk	Low risk	Low risk	Low risk	Low risk
Nahra et al[33]	Randomized	Low risk	26% attrition	Low risk	Low risk	High risk
Rubino et al[34]	Randomized	Low risk	Low risk	Low risk	Low risk	Low risk
Wadden et al[35]	Randomized	Some concerns	Low risk	Low risk	Low risk	Some concerns
Wilding et al[36]	Randomized	Low risk	22% dropout	Low risk	Low risk	High risk
Ji et al[37]	Randomized	Low risk	18% dropout	Low risk	Low risk	Some concerns

RCT = randomized controlled trial.

Figure 2 depicts the rate of weight reduction for the GLP-1 agonists and placebo groups. The weight reduction rate was 78.54% (3231/4114) in the GLP-1 agonist group and 26.53% (772/2910) in the placebo group. Weight loss rates were significantly higher in the GLP-1 agonist group compared with the placebo group (OR: 11.37, CI: 8.10–15.98, P value < .0001). I² was 82%, which indicates high heterogeneity between the included studies.

Figure 2.

Forest plot (the rate of weight loss of the GLP-1 agonists group and the placebo group). CI = confidence interval, GLP-1 = glucagon-like peptide-1, M-H = Mantel–Haenszel.

Figure 3 depicts the number and proportion of patients who lost weight after taking semaglutide or other medications. According to the Lingvay et al study, 51% of those who used semaglutide and 62% of those who used tirzepatide lost weight.^[18] Jensen et al found that 85.7% of those who used semaglutide and 69% of those who used liraglutide lost weight.^[21] Rodbard et al found that 39.9% of those who used semaglutide and 39% of those who used empagliflozin lost weight.^[23] Rubino et al found that 70.9% of those who used semaglutide and 25.6% of those who used liraglutide lost weight.^[24] Ji et al found that 55.2% of those who used semaglutide and 5.9% of those who took sitagliptin lost weight.^[37] Semaglutide was more effective than other agents in reducing weight (OR: 2.98, CI: 0.86–10.25, P value = .08). I² was 98%, which indicates high heterogeneity between the included studies.

Figure 3.

The percentage of people who lost weight after taking either semaglutide or other agents. CI = confidence interval.

Figure 4 shows the number and proportion of patients who lost weight while taking dulaglutide or other drugs. According to Inagaki et al, 10.7% of those who used dulaglutide and 61% of those who used tirzepatide lost weight.^[17] Rosenstock et al found that 2.5% of those who used dulaglutide and 9.5% of those who used tirzepatide lost weight.^[20] Zhang et al found that 36% of those who used dulaglutide and 77.6% of those who used mazdutide lost weight.^[25] The research revealed that dulaglutide is less effective in reducing weight than other drugs (OR: 0.11, CI: 0.06–0.19, P value < .0001). I² was 18%, which indicates low heterogeneity between the included studies.

Figure 4.

The percentage of people who lost weight after taking either dulaglutide or other agents. CI = confidence interval.

Figure 5 shows the number and proportion of patients who lost weight while taking tirzepatide or other drugs. Lingvay et al found that 62% of the individuals who used tirzepatide and 51% of the individuals who used semaglutide lost weight.^[18] Inagaki et al found that 61% of the individuals who used tirzepatide and 10.7% of the individuals who used dulaglutide lost weight.^[17] The present study showed that tirzepatide is more effective than other agents in reducing weight (OR: 4.45, CI: 0.55–35.74, P value = 0.16). I² was 98%, which indicates high heterogeneity between the included studies.

Figure 5.

The proportion of patients who lost weight while taking tirzepatide or other drugs. CI = confidence interval.

Figure 6 shows the number and proportion of individuals who lost weight while on liraglutide or other medications. Silver et al found that 22.7% of those who used liraglutide and 4.5% of those who used sitagliptin lost weight.^[29] Jensen et al found that 69% of those who took liraglutide and 85.7% of those who used semaglutide lost weight.^[21] Rubino et al found that 25.6% of those who used liraglutide and 70.9% of those who used semaglutide lost weight.^[24] The research revealed that liraglutide is less effective in reducing weight than other drugs (OR: 0.55, CI: 0.08–3.79, P value = .54). I² was 84%, which indicates high heterogeneity between the included studies.

Figure 6.

The proportion of individuals who lost weight while on liraglutide or other medications. CI = confidence interval.

Figure 7 and Table 4 show “SUCRA Ranking of Treatments in Network Meta-Analysis.” The most effective medications were tirzepatide (SUCRA score was 91.2% and the probability of being best was 68%), semaglutide (SUCRA score was 85.4% and the probability of being best was 28%), retatrutide (SUCRA score was 78.6% and the probability of being best was 3%), and mazdutide (SUCRA score was 72.1% and the probability of being best was 1%).

Figure 7.

SUCRA ranking of treatments in network meta-analysis. SUCRA = surface under the cumulative ranking curve.

4. Discussion

Obesity is a complicated disease defined by excessive fat buildup that is caused by genetic, environmental, and other influences. Obesity has increased morbidity, disability, and mortality in recent years, posing a significant threat to people’s health and lives while also raising public health care costs. Previous research suggests that weight loss can greatly reduce the risk of obesity-related comorbidities and chronic diseases.^[38] Diet management, moderate exercise, behavior modification programs, bariatric surgery, and prescription drug therapy are the most common strategies to help patients lose weight. Anti-obesity medications, for example, have good compliance rates and produce noticeable short-term results in lowering obesity levels. However, due to safety or efficacy concerns about anti-obesity treatments, many of the existing medications have limited clinical use.^[38] GLP-1 RAs are a class of medications that target incretin hormone function, with receptors found in neurons, islets, the heart, the lungs, the skin, and other organs. Several animal studies and clinical trials have shown that GLP-1 RAs are more successful at treating or preventing obesity.^[38]

GLP-1 agonists, which were initially created to treat T2D, have shown potential as weight loss therapies. These medications, which imitate the effect of GLP-1 hormones, help manage blood sugar levels and decrease hunger, resulting in significant weight loss. GLP-1 agonists are becoming an essential option for obesity management, as evidence from randomized controlled trials (RCTs) grows.^[39–41] Given the growing prevalence of obesity and its related complications, effective pharmaceutical therapies are important. Individual RCTs on GLP-1 agonists have shown encouraging weight loss results, but a meta-analysis provides a more comprehensive assessment of their efficacy by pooling data from several trials. According to Popoviciu et al, GLP-1 agonists used to treat T2D are beneficial in inducing weight loss in both preclinical and clinical investigations.^[16]

This meta-analysis of 16 RCTs involving 7024 participants found that GLP-1 agonists effectively lowered body weight compared with placebo. White et al conducted a study of 2400 people with overweight or obesity and T2D and discovered that initiating a GLP-1a at the normal glycemic control dose resulted in modest weight loss over 72 weeks.^[15] Previous research has shown that individuals with T2D and overweight or obesity who began taking chosen GLP-1 agonists, including doses greater than those generally prescribed for glycemic control, lost clinically significant weight.^[42–44] Vosoughi et al found that 50.2% of individuals treated with GLP-1 RAs experienced ≥5% weight loss.^[45]

Semaglutide and tirzepatide have demonstrated superior weight loss efficacy compared with other GLP-1 RAs. Both drugs beat previous GLP-1 RAs such as liraglutide and exenatide in terms of weight reduction results. Tirzepatide, a newer medication, is a dual agonist since it acts on both the GLP-1 and glucose-dependent insulinotropic polypeptide receptors. It has been demonstrated to be even more effective in weight loss than semaglutide. Jensen et al found that 85.7% of individuals who used semaglutide and 69% of those who used liraglutide lost weight.^[21] Rodbard et al found that 39.9% of individuals who used semaglutide and 39% of those who used empagliflozin lost weight.^[23] Rubino et al found that 70.9% of individuals who used semaglutide and 25.6% of those who used liraglutide lost weight.^[24] Ji et al found that 55.2% of individuals who used semaglutide and 5.9% of those who took sitagliptin lost weight.^[37] Lingvay et al found that 62% of those who used tirzepatide and 51% of those who used semaglutide lost weight.^[18] Inagaki et al found that 61% of those who used tirzepatide and 10.7% of those who used dulaglutide lost weight.^[17]

5. Conclusion

The current meta-analysis of RCTs reveals that GLP-1 RAs are more effective at inducing weight loss than placebo. Among these, semaglutide and tirzepatide have shown higher efficacy, with more significant weight loss than other GLP-1 agonists. These findings highlight the potential of semaglutide and tirzepatide as prominent therapeutic choices for obesity management, promising better outcomes for patients looking for effective weight loss medications.

Author contributions

Funding acquisition: Mohamed Balaha.

Methodology: Nehad Ahmad.

Formal analysis: Nehad Ahmad.

Validation: Nehad Ahmad.

Data curation: Abdulaziz Alruwayyes.

Resources: Abdulaziz Alruwayyes, Amer Alarjani.

Software: Abdulelah Tawhari.

Visualization: Abdulaziz Aldosri.

Supervision: Abdullah Alahmari.

Writing – original draft: Nehad Ahmad.

Writing – review & editing: Mohamed Balaha.