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doi.org/10.36721/PJPS.2021.34.5.SUP.1891-1895.1
Pak. J. Pharm. Sci., Vol.34, No.5(Suppl), September 2021, pp.1891-1895 1891
Effect of nebivolol beneficial on lipid profile and glycemic control in
comparison with Atenolol in patients with type 2 DM with concomitant
hypertension
Abdul Majid1, Amir Javed1, Mazhar Hussain2, Zeeshan Faisal1, Asim Elahi3
and Lubna Akhtar2
1 Department of Cardiology Sheikh Zayed Medical College/Hospital Rahim Yar Khan, Punjab, Pakistan
2 Department of Pharmacology& Therapeutics Sheikh Zayed Medical College/Hospital Rahim Yar Khan, Punjab, Pakistan
3Department of Internal Medicine CHI Saint Joseph Hospital, London, Kentucky, USA
Abstract: Blood pressure control in hypertensive patients with metabolic abnormalities is challenging because many
antihypertensive drugs adversely affect metabolism. Nebivolol a 3rd generation vasodilatory β-blocker offer neutral or
beneficial effects on insulin sensitivity and lipid metabolism. The purpose of this study was to evaluate the effect of
nebivolol and atenolol on glycemic control and lipid profile in type 2 diabetes patients with concomitant hypertension.
We conducted a 12 weeks double blind randomized clinical trial at Sheik Zayed Hospital Rahim Yar Khan. Patients were
randomly divided in to two groups. Patients in group were given tablet nebivolol 5-10mg while patients in group B were
given tablet Atenolol 25-50mg/daily for a period of 12 weeks. Pre and post data were analyzed by SPSS 20. After 12
weeks, Both drugs lowered blood pressure significantly i.e. nebivolol (SBP from152±12 to130±14 with p=0.004, DBP
from 95±12 to78±8.5 with p=0.002) Atenolol (SBP from148±16.5 to 128±15.5 with p=0.006, DBP from 90±10.5 to
82±12 with p=0.003).Similarly both Nebivolol and Atenolol did not any significant effect on glycemic control and lipid
profile at 12 week with in groups. However when comparison was done between two groups, Nebivolol significantly
reduced blood sugar (p₌0.001), HbA1c (p=0.0032), total Cholesterol (p=0.002), triglycerides (p=0.012), LDL-
Cholesterol (p=0.007) and HDL-Cholesterol (p=0.001) as compared to atenolol. In comparison with atenolol, Nebivolol
has a beneficial effect on glycemic control and serum lipid profile.
Keywords: Nebivolol, hypertension, atenolol, blood sugar, lipid profile.
INTRODUCTION
Diabetes mellitus is one of the most prevalent metabolic
disorders and a health change all across the world.
Approximately one out of eleven people have diabetes
with predominantly (90%) type 2 DM. Genetics, a
sedentary life style, urbanization and environment factor
plays a vital role in its pathogenesis (Zheng et al., 2018).
Current prediction reveals that number of diabetic cases
worldwide is expected to rise from 460 million to 700
million in last two decades. Pakistan stands at 4th position
in world diabetes ranking and had 19.4 million people
with diabetes in 2019. The number of diabetic cases is
projected to reach 26.2 million in 2030 if aggressive steps
are not undertaken (Saeedi et al., 2019).
Hypertension is common comorbid condition in diabetes
and vice versa. There is approximately 40% to 60% co
existence of diabetes and hypertension in patients with
type 2 DM. Moreover hypertensive patients often exhibits
insulin resistance and may precede the onset of diabetes
(Tsimihodimos et al., 2018). Cardiovascular disease is the
leading cause of morbidity and mortality in patients with
type 2 DM which is aggravated by hypertension The
cause of strong association between type 2 DM and
hypertension is due to existence of similar risk factors
such as obesity, dyslipidemia, vascular inflammation,
endothelial dysfunction and atherosclerosis (Petrie et al.,
2018).
Nebivolol is a 3rd generation cardioselective beta-
adrenoreceptor antagonist (BAA). In comparison with 1st
and 2nd generation BAA, Nebivolol offer a better
hemodynamic profile due to its vasodilating properties
(do Vale et al., 2019). Nebivolol exercises its vasodilatory
effect through the production of nitric oxide derived from
the endothelium by stimulating the Nitric Oxide Synthase
(NOS) mediated by β3 receptor agonism Nebivolol also
exerts neutral or beneficial effects on insulin sensitivity
and lipid metabolism. It could be a very good option for
hypertensive patients with impaired glucose and lipid
metabolism (Arazi and Gonzalez, 2017). Erectile
dysfunction is quite common in diabetic and hypertensive
patients. Nebivolol has strong potential to improve
erectile dysfunction due to nitrous oxide potentiation.
Nebivolol improves endothelial dysfunction and central
hemodynamics as compared to others BAA. It has also
anti platelets, anti inflammatory, anti proliferative and
antioxidant properties (Olawi et al., 2019).
The main purpose of this study was to compare the effect
of nebivolol and atenolol on serum lipid profile and
glycemic control in T2DM patients with mild to moderate
hypertension.
*Corresponding author: e-mail: mazharhussain214@gmail.com
Nebivolol has beneficial effect on lipid profile and glycemic control in comparison with Atenolol in patients
Pak. J. Pharm. Sci., Vol.34, No.5(Suppl), September 2021, pp.1891-1895
1892
MATERIALS AND METHODS
This double blind randomized clinical trial was conducted
at Sheik Zayed Medical College/Hospital Rahim Yar
Khan from January to March 2020. Consent was obtained
or waived by all participants in this study. Institutional
Review Board, Sheikh Zayed Medical College and
Hospital issued approval 24/IRB/SZMC/SZH. The study
perspectives were clearly explained to all patients and
confidentiality maintained throughout the study period.
Initially 560 type 2 patients were screened at a diabetic
clinic and cardiology outdoor over a period of 03 months
on the basis of presenting complaints such as generalized
body aches & pains, headache, dizziness, dyspnea,
restlessness, anxiety and loss of sleep. Out of which 190
patients were enrolled in the study on the basis of
inclusion and exclusion criteria. The inclusion criteria
were type 2 diabetic patients aged 35-56 years, HbA1c
<8, grade 1 hypertension according to international
society of hypertension criteria (Unge et al., 2020).
Borderline serum lipid profiles according to ATP III
guideline criteria. The exclusion criteria were bradycardia
(<60 beats/min), severe hypertension according to WHO
criteria, poorly controlled diabetes (HbA1c >8) and high
serum lipid profile according to ATP 111 guidelines
criteria. Patients with history of smoking, ischemic heart
diseases, stroke, heart failure and depression were
excluded from the study. In addition detailed history was
taken about secondary causes of dyslipidemia such as
hypothyroidism, pregnancy, alcoholism, chronic kidney
diseases, chronic hepatic diseases, NAFLD, cholestatis,
rheumatoid arthritis, SLE, anabolic steroids, oral
contraceptives, second generation anti psychotics,
corticosteroids, immunosuppressive.
Patients were randomly divided in to two groups. Patients
in group A were allocated even number while patients in
group B were allocated odd numbers respectively through
computed generated software. Patients in both study
groups were blinded to treatment plan. Patients in group
A were given tablet nebivolol 5-10mg while patients in
group B were given tablet Atenolol 25-50mg/daily for a
period of 12 weeks. The dose of each tablet was titrated
with respect to blood pressure. The targeted blood
pressure was below 140/90. If targeted blood pressure
was not achieved within two weeks of anti hypertensive
drug therapy then patients were dropped out from the
study.
Blood pressure was measured twice in right arm at an
interval of 10 minutes through brachial artery by standard
sphygmomanometer apparatus. Body mass index (BMI)
was estimated by known formula weight in kg/height in
m2. A 5ml overnight fasting blood sample was collected
from median cubital vein through aseptic technique using
5cc disposable syringe. This sample was used to analyze
serum sugar and lipid profile though semi automated
chemistry analyzer.
STATISTICAL ANALYSIS
A statistical package for social sciences (SPSS 20) was
used to analyze numeric data which was presented as
mean±standard deviation and percentages. A
Kolomogorov-Smirnov test was used to analyze
continuous variables for normal distribution. To see the
baseline difference between two groups, t-test was
applied. To compare the difference after 12 weeks of
treatment paired t-test was used within groups while
Mann-Whitney U-test and t-test were used between
groups. A p-value <0.05 were seemed to be statistically
significant.
RESULTS
A total of 560 patients were screened, out of which 140
patients were enrolled in the study. The tolerability and
safety profile of both drugs were quite good. There were
no major adverse effects noted in nebivolol group.
However three patients in the atenolol group developed
severe bradycardia and five patients complaint fatigue
were dropped out from the study. Blood pressure of four
patients was not responded to nebivolol in spite of
maximum dose titration. Six patients in nebivolol group
and four patients in the atenolol group could not complete
the study because of loss in follow up. A total 118
patients completed the study 60 in group A and 58 in
group B. These have shown in fig. 1.
There was no significant statistical difference in baseline
demographic and clinical characteristics between two
study groups at the start of study (table 1).
However at 12 weeks, Both drugs lowered blood pressure
significantly i.e. nebivolol (SBP from152±12 to130±14
with p=0.004, DBP from 95±12 to78±8.5 with p=0.002)
Atenolol (SBP from148±16.5 to 128±15.5 with p=0.006,
DBP from 90±10.5 to 82±12 with p
₌0.003).Similarly
both Nebivolol and Atenolol did not any significant effect
on glycemic control and lipid profile at 12 week with in
groups. However in comparison with Atenolol, Nebivolol
significantly reduced blood sugar (p₌0.001), HbA1c
(p=0.0032), total Cholesterol (p=0.002), triglycerides
(p=0.012), LDL-Cholesterol (p=0.007) and HDL-
Cholesterol (p=0.001) table 2.
DISCUSSION
There is quite variation in determining the effect of
nebivolol on glycemic control and serum lipid profile in
type 2 diabetic patients in various clinical studies. Some
studies revealed that nebivolol exerts beneficial effects,
while others studies found neutral or no significant effects
on dyslipidemia and insulin sensitivity (Walczak-
Gałęzewska et al., 2018; Kwon et al., 2018; Marketou et
al., 2017).
Mazhar Hussain et al
Pak. J. Pharm. Sci., Vol.34, No.5(Suppl), September 2021, pp.1891-1895 1893
Fig. 1: Study Flow chart
Table 1: Baseline characteristics and clinical parameters of patients (N=118)
Baseline parameters Nebivolol (n=60) Atenolol (n=58) P-value
Age(years) 32±11 36±15 0.36
Gender (M/F) 34/20 36/19 0.86
Body weight(kg) 92±12.5 84 ±15 0.07
BMI (Body Mass index kg/m2) 32±2.5 29 ±5.5 0.04
Blood pressure Systolic (mmhg) 152±12 148±16.5 0.42
Blood pressure Diastolic (mmhg) 95±12 90±10.5 0.07
Blood sugar fasting(mg/dl) 100±16 95±22.5 0.031
HbA1c 7.8±4.2 8.6±2.8 0.92
T-test between two groups
Table 2: Comparison of the changes at baseline and end point within and between two groups
Study Parameters Nebivolol(60) P value* Atenolol(58) P value* P value+
Baseline End Point Baseline End Point
SBP 152±12 130±14 0.004* 148±16.5 128±15.5 0.006* 0.72
DBP 95±12 78±8.5 0.002* 90±10.5 82±12 0.003* 0.87
Blood Sugar 100±16 90±14.8 0.71 95±22.5 115± 18 0.65 0.001+
HbA1C 7.8±4.2 7.4±3.8 0.83 8.6±2.8 9.2±3.4 0.97 0.0032+
Total Cholesterol 200±22 192±18 0.32 186±32 220±28 0.88 0.002+
Triglycerides 180±35 174±28 0.84 170±26 182±22 0.21 0.012+
LDL-Cholesterol 156±19 150±16 0.67 148±28 158±32 0.46 0.007+
HDL-Cholesterol 38±4.5 42±5.2 0.22 40±3.6 37±4.5 0.32 0.001+
* Significantly (p<0.05) comparison within groups
+ Significantly (p<0.05) comparison of changes of each variable between the two groups.
Nebivolol has beneficial effect on lipid profile and glycemic control in comparison with Atenolol in patients
Pak. J. Pharm. Sci., Vol.34, No.5(Suppl), September 2021, pp.1891-1895
1894
The purpose of present study was to determine the effect
of nebivolol on glycemic control and serum lipid profile
in type 2 diabetic patients with mild to moderate
hypertension in comparison with atenolol. The results of
our study showed that both drugs significantly reduced
blood pressure. However in comparison with atenolol,
nebivolol significantly improved glycemic control and
serum lipid profile.
The results of our study were in consistent with Badar et
al., 2011 who revealed that although both nebivolol and
atenolol had significantly reduced blood pressure but
nebivolol has significantly improved deranged serum lipid
profile and blood sugar as compared to atenolol over a
period of 6 months. Similarly Ozyıldız et al., 2017
showed that vasodilating beta blockers carvedilol and
nebivolol significantly improved serum glucose, serum
insulin, HOMA-IR, total cholesterol, HDL-Cholesterol,
LDL-cholesterol and apolipoprotein B in patients with
essential hypertension.
In comparison with our study Van Bortel LM, 2010
pointed out that nebivolol significantly reduced total
cholesterol, LDL-Cholesterol and LDL/HDL cholesterol
ratio. However no significant effects were recorded on
serum triglycerides and HDL- cholesterol in hypertensive
patients with concomitant diabetes. On the other hand
nebivolol significantly improved all lipid profile
parameters in our study. A study conducted on more than
2500 hypertensive patients with concomitant type 2
diabetes concluded that nebivolol at a dose of 5mg/day
significantly reduced blood pressure. This blood
pressure reduction was accompanied by improvement in
lipid level, HbA1c and microalbuminuria over a period
of 3 months. Our study showed similar results but we
did not analyzed microalbuminuria (Schmidt et al.,
2007).
Eight randomized clinical trials and three observational
studies of 4 weeks to 6 months duration summarized that
nebivolol displayed neutral or beneficial effects on insulin
sensitivity and lipid metabolism in hypertensive patients.
These studies concluded that nebivolol could be a good
therapeutic option in obese, metabolic syndrome and
diabetic patients with concomitant hypertension
(Marketou et al., 2017). Similarly in another randomized
controlled trial tolerability and safety profile of nebivolol
is better than atenolol in patients of essential hypertension
(Bhosale et al., 2014).
A meta analysis of eight randomized controlled trial
demonstrated that in comparison with 2nd generation β-
blockers, nebivolol was significantly better tolerability
profile with lower risk of adverse effects (Liu et al.,
2020). A nationwide multicentre cohort study pointed that
vasodilating β-blockers resulted in better clinical outcome
then conventional β-blockers in patients with acute
myocardial infarction after percutaneous coronary
intervention (Chung et al., 2017). Microalbuminuria is an
early predictor of renal and cardiovascular events in
hypertensive and diabetic patients. In a small sample
study nebivolol significantly reduced microalbuminuria in
hypertensive patients with or without diabetes (Merugu
and Bingi, 2020). Endothelial dysfunction is quite
common in diabetics and hypertensive patients. Nebivolol
has a strong potential to improve endothelial dysfunction
due its antioxidant and anti inflammatory properties.
Seeing these pleiotropic effects of nebivolol it can be
safely used in diabetic patients with cardiovascular
disease and other comorbidities.
CONCLUSION
In comparison with atenolol, Nebivolol has a beneficial
effect on glycemic control and serum lipid profile. It can
be safely used in hypertensive patients with concomitant
diabetes.
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