Effect of Glucagon-like peptide-1 agonist (liriglutide) on weight and glycemic control among adults with type 2 diabetes mellitus attending primary care center at security forces hospital in Riyadh, Saudi Arabia.

INTRODUCTION: Liraglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 receptor agonist), also known as incretin mimetics. This is the new approach for management of weight among diabetic patients along with glycemic controls. The study aims to explore the efficacy of Liraglutide on weight (body mass index) and glycemic control (HbA1C) among adult patients with type 2 diabetes mellitus in primary care center.
METHODS: Retrospective chart review of 149 adult patients with type II diabetic taking Liraglutide as a monotharepy for 6 months and more were included in the study. Analysis was done in SPSS version 22.
RESULTS: Total 149 chart reviews were done. The mean age of participants were 55.52 (SD: 8.167). Of total 58.4% were female and 70% were on insulin. Paired sample statistics reported that pre- and post-change in BMI and weight was significantly different with P value < 0.001. However pre- and post-change in the value of HBA1c was not significantly different with P value 0.561.
CONCLUSION: Through this retrospective study we can conclude that Liraglutide has important effect on weight loss and reduction in BMI. However, further longitudinal studies with large sample size and multi-center randomized controlled trials are needed to generalize the effectiveness of Liraglutide among Saudi population. Copyright:

Introduction and Literature Review

Diabetes mellitus is a chronic metabolic disease in which blood glucose level increases either due to deficiency in insulin production or fewer efficacies, or both.[1] Worldwide, 415 million people suffered with diabetes and 5 million death occurred due to diabetes in 2015 and it is anticipated that diabetes population will increase to 642 million by 2040[2] As per the IDF Diabetes Atlas every 7 s someone is dying because of diabetes or because of the complications due to diabetes and half of those deaths are among the age group 60 and below.[3] Diabetes is associated with many other chronic illnesses including kidney failure (>50%), certain cardiovascular diseases (70%), vision loss, and other related diseases.[3]

Raising prevalence and high double burden of disease have led to various means of managing the blood glucose level, the major goal of the treatment. Type II diabetes usually managed through non-insulin medications, insulin, weight reduction, and lifestyle and dietary modifications. Choice of treatment and particular medication depends on individual's health status, effectiveness of particular medication, side effects, compliance and lastly economical constrains. The line of actions varied with respect to particular type of medication for example some medication aims at increasing the sensitivity of the insulin while other increases the glucose excretion, some medication decreases the absorption of carbohydrates while other medications work differently to manage blood glucose level.[4]

With the aim of identifying the true class of drugs that target the root cause of diabetes which all modern medication has failed to do so, Glucagon-like peptide analogues represents the most recent and unique invent which is true anti-hyperglycemic used in the treatment of type 2 diabetes by targeting beta cell failure, brain, alfa cells, gastrointestinal tract, and insulin resistance.[5]

Liraglutide is one of the GLP-1 analogues used in type 2 diabetes treatment. Recent studies have shown that Liraglutide had good glycemic control without risk of hypoglycemia[6] with moreover benefits correlated to weight loss.[7] Despite of these benefits, Liraglutide mainly used as a second and third-line agent via different national and international diabetes associations.[8]

A recent systematic review and meta-analysis of five RCTs involving 1,440 participants showed that patient treated with 1.2 mg and 1.8 mg Liraglutide combined with metformin could remarkably decrease the level of glycosylated hemoglobin (HbA1c) (P < .00001, MD=-0.35, 95% CI -0.51 to -0.20). Moreover, patients on 1.8 mg Liraglutide also had notable weight loss (P < .00001, MD=-1.12, 95% CI -1.54 to -0.70).[9]

A retrospective study done in Italy on 2018 showed that 577 (43.5%) out of 1,325 patients treated with Liraglutide achieved HbA1c ≥1.0% (10.9 mmol/mol) in 12 months.[10] A new research found that T2DM patients taking GLP-1 antagonist like liraglutide showed improved cardiovascular outcomes.[11]

A recent study with large number of obese female participants with average 10% reported decrease in HbA1c 1.7% (18 mmol/mol) (P value < 0.001), while overall weight reduces -1.8 kg (P value 0.001) after the initiation of Liraglutide.[12]

The primary care physicians are the doorkeepers who recognize, diagnose, and treat mostly type 2 diabetic and obese patients. Whereas most of the patient came to primary care were treated by general practitioner or family medicine doctor for many years and they were fully understand their patients' disease status. Therefore, we conduct the study in primary care setting. Thus the study aims to evaluate the efficacy of Liraglutide on weight (body mass index) and glycemic control (HbA1C) among adult patients with type 2 diabetes mellitus in primary care center.

Methodology

We conducted a retrospective cohort study started from 1st January 2018 and ended at 1st of December 2018. We included all the adults of age 18 and above with type II diabetes who were taking Liriglutide for 6 months and more. The study was conducted in the primary care center in the Security Forces hospital, Riyadh, KSA. We excluded all those patients with Type 1 Diabetes Mellitus patients; those who were pregnant or had gestational diabetes and patients with added other antidiabetic medications during the study period. By using the hospital recoded 300 random patients were selected and were approached. Those fulfiling the inclusion exclusion criteria and who consented for participation were included in the study. Total 149 patients were included in this study.

Ethical approval

Ethical approval was obtained from the Hospital research ethical committee in security forces hospital, Riyadh.

Variables measured

Following data were obtained from database; age of patient, gender, HbA1c before and 6 months after Liraglutide prescribed, body mass index before and 6 months after Liraglutide prescribed and also information on the intake of insulin.

Plan of analysis

Data were entered into SPSS statistic software version 22 and descriptive analyses are reported. Mean and standard deviation for continuous variables and frequency and percentage for categorical variables are reported. Paired t-test and independent t-test are used to report any changes in pre and post-states. P value 0.05 and less is considered significant.

Results

Total 149 chart reviews were done. The mean age of participants was 55.52 (SD: 8.167). Minimum age of the cohort was 32 and maximum 79. Of total 58.4% were female and 70.5% were on insulin [Figures 1 and 2] Mean weight before the start or regimen was 101.68 (SD: 20.48) which was reduced to 99.35 (SD: 19.68) after starting the medication with the mean difference of 2.32 (SD: 7.69). Mean BMI before the start or regimen was 38.74 (SD: 7.13) which was reduced to 37.84 (SD: 6.73) after starting the medication with the mean difference of 0.9006 (SD: 2.98). Likewise, mean HBA1c was 9.27 (SD: 1.83) before the start of regimen which was dropped to 8.99 (SD: 5.92) after Liraglutide medication with the mean difference of 0.27 (SD: 0.50) [Table 1].

Figure 1

Distribution of study participants with respect to gender (N = 149)

Figure 2

Intake of insulin among study participants (N = 149)

Table 1

Mean and standard deviation of variables before and after the intake of Liraglutide (n=149)

Variables	Mean and SD
Age	55.52 (8.16)
Weight before	101.68 (20.48)
Weight After	99.35 (19.68)
BMI before	38.74 (7.13)
BMI After	37.84 (6.73)
HbA1c before	9.27 (1.83)
HbA1c after	8.99 (5.92)

Paired sample statistics reported that pre and post-change in BMI and weight was significantly different with P value < 0.001. However, pre and post-change in the value of HBA1c was not significantly different with P value 0.561.

Mean difference of pre and post-BMI and weight change did not differ with respect to gender with P value 0.397 and 0.608, respectively. Likewise, pre and post-HBA1c did not differ with respect to gender with P value 0.144. Likewise, mean difference in pre and post-weight, BMI, and HBA1c did not differ with respect to insulin intake with P value 0.642, 0.448, and 0.841, respectively.

Discussion

This retrospective study on 149 patients taking Liraglutide for 6 months and more reported that there was significant reduction in post-regimen weight and BMI reduction however the reduction in HBA1c was not significantly differed. Our findings also showed that this reduction was irrespective of gender and insulin intake.

Our findings are consistent with the findings of the other studies in the past reporting significant reduction in weight loss due to Liraglutide. HbA1c was reduced post-treatment but the reduction was not statistically significant as reported in other studies. Globally different studies have reported the effect on both weight and glycemic control.[12131415] Our results are in line with the findings of these studies. However, recently a study conducted in Saudi Arabia reported no effect of Liraglutide on the weight reduction.[16] The same study reported significant reduction in HbA1c for the patients taking 1.2 mg dose, however the effect was not significant for the patients taking 0.6 and 1.8 mg dose. In the current study we were not able to access the information regarding the dosage of Liraglutide, however we did not find any significant reduction in the levels of HbA1c. Differences in the findings of our study could be related to study population, sample size, inclusion and exclusion criteria and also we only took patients who were using Liraglutide as monotherapy while the study conducted by Yasser et al. studied effect of Liraglutide when taken with other treatment regimens.[16]

The findings of our study should be interpreted with keeping in consideration all the limitations which are as follows: firstly this is a single centered study thus we cannot generalize the findings of our study. Secondly the sample size was comparatively larger than the former studies conducted in Saudi Arabia yet not feasible for generalizability of the findings. Thirdly the nature of study design also imposes many limitations like the effects of confounding and non-randomization. Fourth we were unable to access other important information like dosage, total duration of regimen and compliance which could affect the findings.

Despite of all these limitations our study imposes a great piece of knowledge in the pool of literature by highlighting the effectiveness of Liraglutide on weight loss, which could benefit the problem of obesity and could modify the effect of treatment by controlling the excessive weight gain. Further longitudinal and randomized controlled trials are needed to be conducted in Saudi Arabia specifically in order to evaluate the true effect of the drug among patients.

Conclusion

Through this retrospective study we can conclude that Liraglutide has important effect on weight loss and reduction in BMI. However, further longitudinal studies with large sample size and multi-center randomized controlled trials are needed to generalize the effectiveness of Liraglutide among Saudi population.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her consent. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.