Effect of mirabegron on lipid profile (serum cholesterol and triglyceride) in Iraqi patients with overactive bladder

Weight and height to calculate body mass index by equation¹⁶

During the baseline assessment of the patients:

The weight in kilograms divided by the square of the height in meters yielded the body mass index, or BMI (kg/m²). In accompanying study, women accompanying a BMI of ≤18.5 were classified as thin, those accompanying a BMI of 18.5-24.9 were deliberate to have normal weight, women accompanying a BMI of 25-29.9 were classification as obese, and women accompanying a BMI of ≥30 were marked as corpulent.¹⁷

The lipid profile included the measurement of fasting serum cholesterol and triglyceride levels

Venous blood samples were collected from 6 hour fasting patients using plastic tubes with gel barriers. These gel barriers, being a pure substance, are highly stable in terms of their physical and chemical properties. After centrifugation, the collected samples were separated into serum or plasma from blood cells. Both serum and plasma were deemed acceptable specimens. The gel barrier effectively separated the serum from fibrin and cells post-centrifugation, thereby preventing the exchange of substances between blood cells and serum. This process maintained the biochemical characteristics and chemical components of the serum for an extended period. The levels of serum cholesterol and triglycerides were analyzed using the Architect c4000 analyzer (Abbott Diagnostics^®, USA). This system is a high-throughput clinical chemistry analyzer capable of performing up to 800 tests per hour. For more information, visit Abbott Diagnostics at [https://www.corelaboratory.abbott/int/en/home.html].

During the first follow-up visit (2 months after the baseline assessment), the patients’ weight and subsequent changes in body mass index, as well as fasting serum cholesterol and triglyceride levels, were measured.

In the second follow-up visit (2 months after the first visit), the same parameters were assessed as in the initial visit. Out of the total 40 patients, only a subset completed the follow-up assessments.

Statistical analysis

The data were analyzed using statistical package for social sciences (SPSS) version 22. The data were presented as mean ± standard deviation. paired t-test was used for compare the mean of continuous variable in the study. Level of P-value less than 0.05 was considered significant.

Baseline characteristic

The total sample included in this study was 40 patients, of whom 60% were female and 40% were male, and the mean age of participants were 50.7±18.12 years. Regarding the height and weight of the sample, the results showed that the mean of height and weight were (163.65±8.393 m and 77.25±12.09 kg respectively) as shown in Table 1.

At baseline time, the result of study showed the mean of BMI were (29.02±5.216 kg/m²), while the mean of s. cholesterol and s. triglyceride were (192.33±33.300 mg/dl and 142.62±29.127 mg/dl respectively) as shown in Table 1.

Parameter after 2 months of treatment

Two months later, we reevaluate the same parameters from our sample and discover that the mean BMI has dropped to 28.82±64.926 kg/m². Moreover, the results showed that the mean serum cholesterol level (196.45±30.932 mg/dl) was higher than the baseline level, whereas the mean triglyceride level (130.2±27.936 mg/dl) was lower. Considering Table 2.

Parameter after 4 months of treatment

four months later, when we reevaluate the same characteristics from our sample, discover that the mean BMI has slightly fallen to (28.62 ±4.859 kg/m²). As show in Figure 1 and Table 3.

Figure 1. BMI, cholesterol and triglyceride mean of study sample after the use of mirabegron.

Additionally, the mean triglyceride level (121.25±27.554 mg/dl) decreased while the mean cholesterol (199.90±24.746 mg/dl) marginally increased. As shown in Figure 1 and Table 3.

The effect of treatment with mirabegron

After 2 months

According to the study’s findings, there is no a statistically significant correlation between the mean BMI and S. cholesterol after two months (p=0.114,0.227 respectively). However, the results, as indicated in Table 4, reveal a statistically significant difference among mean of S. triglycerides after 2 months (p=0.001).

After 4 months

The outcomes of the study demonstrate that after four months, there is a statistically significant link (p=0.001) between the mean triglyceride, but not between BMI and S. cholesterol (p=0.562, 0.261 respectively). According to Table 5.

Therapy effect on TG and BMI

After a period of two to four months under the mirabegron presidency, the study sample displayed a decrease in both mean BMI and plasma triglyceride levels. This finding is in line with a review conducted by Dąbrowska AM and colleagues, which highlights the importance of two distinct types of adipose tissue, each with its own unique physiological function. The activation of the thermogenic tissue-specific uncoupling protein 1 (UCP1) plays a crucial role in the metabolism of glucose, fatty acids, and other substances to generate heat in brown adipose tissue (BAT), including the associated “beige”/“brite” adipocytes derived from white adipose tissue (WAT). In situations where energy intake exceeds expenditure, WAT is responsible for storing excess triglycerides.¹⁹ There is emerging evidence suggesting that BAT may have potential therapeutic applications in adult humans. β3-adrenergic receptors (ARs) are expressed not only in brown and white adipocytes but also in the urinary bladder. Adipocytes in both white and brown adipose tissue may be stimulated to undergo thermogenesis by a β3-adrenergic agonist such as mirabegron that is currently being studied. These adipose tissue types hold thermogenic fat containers, and their incitement holds promise as a creative policy for combating corpulence by growing strength energy expenditure.^20,21 Numerous clinical troubles and exploratory research have illustrated the impact of mirabegron on two together body mass and BAT activity. The authors noticed that mirabegron increased BAT exercise and resting energy expenditure.²² Preliminary data desires that mirabegron may have comparable effects to light exercise on the metabolism of triglycerides, bile acids, HDL, and glucose.²³ Ying Z and others found that later four and twelve weeks of situation, the levels of plasma lipids were judged following a four-time fasting period. Mirabegron usually diminished plasma triglyceride levels. Despite the plasma HDL-cholesterol waited unaltered at either time points, there was a leaning towards diminished plasma triglycerides following in position or time 12 weeks of mirabegron treatment.²⁴ Body mass index (BMI) was included in this particular study to assess the effect of the treatment on body weight. However, proficient was no statistically significant change in BMI (p=4.546), regardless of few decrease in the figures. In contrast, Cypess and others executed a study place 12 healthy men were performed 200 mg of oral mirabegron often for 12 weeks. The group receiving mirabegron demonstrated a 203±40 kcal per day rise in basal metabolic rate and an increase in BAT activity, which was known to those who took a placebo. According to the researchers’ calculations, weight reduction through energy expenditure might be as much as 5 kg in the first year and 10 kg in the next three years. Despite the fact that mirabegron was prescribed off-label to treat overactive bladder syndrome in the majority of trial participants, it was generally well tolerated. The most frequent side effects that have been authorized seen was tachycardia.²⁵ Another study by Loh and so forth established indicates there was a notable rise in energy expenditure following the management of 100 mg and 200 mg doses of mirabegron, but skilled was no significant unlikeness from direction following the 50 mg of mirabegron.²⁶ Zhao and others throwed a complex remedy approach promoting metformin and mirabegron for the preventation and treatment of obesity. Through this approach, the summed and spent energy are dealt with at the same time, which does not have any negative impact on cardiac and vascular system. In the prevention model, the association of metformin and mirabegron grown in additional reductions of 12 percent and 14 percent in raised body weight inferred by an extreme-fat diet, separately, distinguished to handling metformin or mirabegron singular. In the treatment model, the alliance of metformin and mirabegron managed to a 17% decrease in body weight in fat rodent convinced by a diet, that was 13 portion and 6 portion more having movement than exploiting metformin or mirabegron distinctively, independently.²⁷ Animal studies have demonstrated that the administration of mirabegron reduces obesity; however, there is no trustworthy proof that patients with obesity who have received mirabegron medication have significantly lost weight. The brief trial time period and confined participant volume may be the reasons for this. Especially, extreme doses of mirabegron were the most effective treatment for adipose tissue stimulation in humans, and a long-term safety assessment is still necessary.²⁸

Therapy effect on fasting plasma cholesterol

The study found no evidence of statistically significant variations in serum cholesterol levels amongst participants treated with mirabegron with respect to the medication’s impact on fasting plasma cholesterol (p=0.227). Nevertheless, further trial is authorized to sufficiently acknowledge the impact of mirabegron on cholesterol and lipid levels. This finding of this study are inconsistent with those of Finlin BS et al., who observed statistically significant decrease in cholesterol following the administration of mirabegron for 12 weeks.²⁹ Certain studies have recorded that the incitement of the β3-adrenoreceptor, furthered by mirabegron, leads to a significant increase in ApoA-1, a critical protein component of HDL in plasma. HDL plays a awake act in mobile cholesterol from tissues to the liver for evacuation.³⁰ In a study executed by Sui and so forth., it was seen that adult rodent incomplete in Apo lipoprotein E (Apo-E) and LDL-receptor shown raised plasma levels of total cholesterol and LDL-C after being treated with mirabegron (8mg/kg/term) for 6 weeks.³¹ Also, another study demonstrated that rats enhance an extreme-fat diet experienced an outdoing in their lipid description following in position or time 12 weeks of situation accompanying two differing doses of mirabegron (5 mg/kg/age and 10 mg/kg/day). This bettering was from a decrease in total cholesterol, triglycerides, and LDL-C levels, in addition to an increase in HDL-C serum levels, recognized to non-treated rats. To completely understand the impact of mirabegron on cholesterol in humans, supplementary research is necessary. Various factors, such as diet and mutations in ApoA-1, Apo-E, or LDL-receptor action, can influence serum cholesterol levels.³²

Ethics and consent

Ethics and research participation consent form

This study was carried out according to the tenets of the Declaration of Helsinki. It was also approved by the Research Ethics Committee of University of Baghdad’s College of Medicine, Registration number: 03-28 date: 21/12/2023. In the first part, forty Iraqis suffering from OAB in Medical City Complex from January 2024 to June 2024 were collected. All patients gave their written informed consent to participate in the study. These patients were treated with 50 mg/day mirabegron for four months, and the results of such treatment were observed.

The following consent form is designed to explain the purpose, procedures, and rights involved in participating in the study, Effect of Mirabegron on Lipid Profile (Serum Cholesterol and Triglyceride) in Iraqi Patients with Overactive Bladder.

“I hereby give my consent to participate in the study and to allow the use of my medical records in the research. The researcher has committed not to share my personal information, and I reserve the right to withdraw my participation at any time. I have been informed that the study may require several blood draws (phlebotomies) and body weight measurements”.