Journal of Medical Science Advances

Comparative Study of Glibenclamide and Glimepiride in Type

2 Diabetes in Rural Population, Andhra Pradesh
Kudaravalli J. and Lakshmi G. V.

J Med Sci Adv 2012, 1(1): 17-20

Online version is available on: www.grjournals.com

KUDARAVALLI AND LAKSHMI

Original Article

Comparative Study of Glibenclamide and

Glimepiride in Type 2 Diabetes in Rural Population,
Andhra Pradesh

Kudaravalli J. and Lakshmi G. V.

Department of Pharmacology, Bhaskar Medical College, Yenkapally(V), Moinabad(M), RR district, Andhra Pradesh, India-500075

Abstract
Controlling blood glucose levels for people with type 2 diabetes often requires several strategies. Weight
loss usually improves blood glucose levels for people with type 2 diabetes. Standard oral hypoglycemic
regimens include single drugs (monotherapy) like sulfonylurea, glibenclamide and glimepiride. This
summarizes evidence from both observational studies and controlled trials that compare the effectiveness and
safety of oral hypoglycemic.

Key word: Blood glucose, Type 2 diabetes, Glibenclamide, glimepiridevc

Corresponding author: Department of Pharmacology, Bhaskar Medical College, Yenkapally(V), Moinabad(M), RR district, Andhra Pradesh, India-500075

17

J. Med. Sci. Adv., 2012, 1(1):17-20

COMPARATIVE STUDY OF CLIBENCLAMIDE AND GLIMEPIRIDE IN

Introduction
Diabetes is due to increased glucose levels and
increased glucose resistance. Controlling blood
glucose levels for people with type 2 diabetes often
requires several strategies. The clinical approach
begins with lifestyle modifications, including
increased
physical
activity
and
diet
control(Alexander GC, et al., 2008). Weight loss
usually improves blood glucose levels for people
with type 2 diabetes. However, many also need oral
medications or insulin (United Kingdom
Prospective Diabetes Study 24, 1998). There is a
large body of clinical evidence that can help inform
decisions about hypoglycemic medications. This
summarizes evidence from both observational
studies and controlled trials that compare the
effectiveness and safety of oral hypoglycemic
(Ohkubo Y et al., 1995). Standard oral
hypoglycemic regimens include single drugs
(monotherapy) like sulfonylurea, glibenclamide and
glimepiride(UK Prospective Diabetes Study
(UKPDS 34) Group,1998, UK Prospective Diabetes
Study (UKPDS) Group,1998). Choosing among
available oral hypoglycemic requires consideration
of their benefits as well as their adverse effects and
cost. It does not include evidence about the
effectiveness of diet, exercise, and weight loss.
Materials and Methods
The study was conducted on diabetic patients
who were attending outpatient department in
Bhaskar Medical College, Yenkapally village,
Andhra Pradesh, India. 100 diabetic patients and 24
healthy controls were recruited. Ethical committee
approval was taken. Informed consent was taken. It
is a single-center, randomised, placebo- controlled,
cross-over study was conducted to characterize the
new sulfonylurea glimepiride and to compare its
profile of action with the second generation
sulfonylurea glibenclamide. The total duration of
each experiment was 5 hours. At zero time an i.v.
injection of 2 and 4 mg glimepiride, 1 mg
glibenclamide or placebo was given i.v. to 24
healthy volunteers. Blood samples were collected
for three hours after the injection (0-3 hours,
preprandial experiment). At 3 hours, a standard
18

mixed meal was given (20%, of a 30 Kcal/Kg Body

Weight diet) and blood samples were collected for 2
more hours (postprandial experiment).
Results and Discussion
Pre-prandially (0-3 hrs) blood glucose
(expressed as the area under the curve divided by
the time) was significantly lower (p < 0.0001) after
the administration of 2 and 4 mg glimepiride (3.7
+/- 0.24 and 3.5 +/- 0.3 mM respectively) compared
to placebo (4.63 +/- 0.31 mM), but not compared to
glibenclamide. Insulin was not different after
glimepiride or glibenclamide. Both glimepiride and
glibenclamide had similar effects on insulin
secretion. Post-prandially (3-5 hrs) blood glucose
was significantly higher after glibenclamide (6.54
+/- 0.8 mM) (p < 0.0001) than after 2 mg
glimepiride (5.75 +/- 0.5 mM). Despite this Cpeptide was significantly higher (p < 0.002)
glibenclamide (5.7 +/- 1.5 ng/ml) compared to
glimepiride (5.1 +/- 1.3 ng/ml); the trend was the
same for insulin but the results were not
significantly different (p = 0.06).
The goals of pharmacologic therapy are to
reduce symptoms of hyperglycemia and the longterm complications of diabetes. Glycemic control is
known to reduce the risk for microvascular
complications,
including
retinopathy
and
neuropathy. The risk for death from cardiovascular
disease is increased in adults with type 2 diabetes
(Gerstein HC et al.,2008); however, it is unclear
whether intensive glycemic control reduces that risk
(Shichiri M et al., 2000; Holman RR et al., 2008).
To make well-informed choices among the options
for achieving glucose control, clinicians and
patients need comprehensive information about the
effectiveness and the safety of therapies, with
attention to patient-relevant outcomes (Bolen S et
al., 2007; Bolen S et al., 2007).
The Agency for Healthcare Research and
Quality published its first systematic review on the
comparative effectiveness and safety of oral
hypoglycemic medications for type 2 diabetes in
2007 (Rockville, MD et al., 2007; Kahn SE et al.,
2006). The agency requested an update of this
review to include medication classes newly
approved by the U.S. Food and Drug
J. Med. Sci. Adv., 2012, 1(1):17-20

KUDARAVALLI AND LAKSHMI

Administration
(FDA)
and
evidence
on
combinations of medications, including oral
medications combined with insulin (Nathan DM et

al., 2009; Rodbard HW et al., 2009; Temple R et al.,

2000).

Table1: Comparision of parameters of Sulfonylurea drugs at fasting and post-prandially.

Parameter
Glibenclamide Glimepiride(2mg) Glimepiride(4mg) HealthyControls
Number
50
25
25
24
Age
55+8yr
53+9yr
56+6yr
55+6yr
Sex
Female
26
12
13
12
Male
24
13
12
12

p-value
-

Blood
Glucose
Fasting

3.7 +/- 0.24mM

3.5 +/- 0.3 mM

4.63 +/- 0.31 mM

<0.0001

Post Prandial
(3-5hr)

6.54 +/- 0.8 mM

5.75 +/- 0.5 mM

C-peptide

5.7 +/- 1.5 ng/ml

5.1 +/- 1.3 ng/ml

The inclusion of additional trials and drug

comparisons since the 2007 review did not provide
sufficient evidence to definitively support one drug
or combination of drugs over another for long-term
clinical outcomes of mortality and macrovascular
and microvascular complications of diabetes
(United Kingdom Prospective Diabetes Study
24,1998; U.K. prospective diabetes study. II, 1985;
United Kingdom Prospective Diabetes Study
(UKPDS). 13,1995; Patel A et al,2008).
Sulfonylureas were consistently associated with
weight reduction or neutrality compared with most
other diabetes medications, which generally
increased weight. Overall, medication effects on
lipid levels were small to moderate and of uncertain
clinical importance. Conclusions on comparative
risk for adverse events were clearest for
sulfonylureas, which increased the risk for
hypoglycemia (Nissen SE et al., 2008; Kumar.A et
al., 2012; Kamoun.M et al., 2012).
Conclusion
In the fasting state, glimepiride and glibenclamide
had similar effects on the changes in blood glucose
levels after i.v. administration. After the meal, less
pronounced hyperglycemia and lower insulin and
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J. Med. Sci. Adv., 2012, 1(1):17-20

<0.0001

<0.002

C-peptide levels following glimepiride (2 mg)

suggests either that glimepiride induces insulin
secretion through a pathway which is different from
that of glibenclamide or that glimepiride facilitates
insulin action through extrapancreatic effects.
Acknowledgements
We are conveying thanks to medicine
department and a special thanks to principal of
Bhaskar Medical College.
Reference
Alexander GC, Sehgal NL, Moloney RM, Stafford RS
(2008). National trends in treatment of type 2 diabetes
mellitus, 1994-2007. Arch Intern Med. 168:2088-94.
Bolen S, Feldman L, Vassy J, Wilson L, Yeh HC,
Marinopoulos S (2007). Systematic review: comparative
effectiveness and safety of oral medications for type 2
diabetes mellitus. Ann. Intern. Med. 147:386-99.
Bolen S, Wilson L, Vassy J, Feldman L, Yeh J, 2007.
Marinopoulos S, et al. Comparative Effectiveness and
Safety of Oral Diabetes Medications for Adults with
Type 2 Diabetes. Rockville, MD: Agency for Healthcare
Research and Quality.
Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT
(2008). Action to Control Cardiovascular Risk in

COMPARATIVE STUDY OF CLIBENCLAMIDE AND GLIMEPIRIDE IN

Diabetes Study Group, Affects of intensive glucose
lowering in type 2 diabetes. N Engl J Med. 358:2545-59.
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil
HA. 10-year follow-up of intensive glucose control in
type 2 diabetes. N Engl J Med. 359:1577-89.
Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR,
Jones NP (2006). ADOPT Study Group. Glycemic
durability of rosiglitazone, metformin, or glyburide
monotherapy. N Engl J Med. 2006;355:2427-43.
Kamoun.M, Jemmali.B, Selmi.H (2012). Monitoring Milk
Urea Level and Feed Ration as a Potential Tool for Milk
Quality. J. Phys. Pharm. Adv. 2(1): 69-76.
Kumar.A, Rinwa.P, Sharma.N (2012). Irritable Bowel
Syndrome: a Review. J. Phys. Pharm. Adv., 2(2):97-108.
Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman
RR, Sherwin R (2009). American Diabetes
Association. Medical management of hyperglycemia in
type 2 diabetes: a consensus algorithm for the initiation
and adjustment of therapy: a consensus statement of the
American Diabetes Association and the European
Association for the Study of Diabetes. Diabetes Care. 32
:193-203.
Nissen SE, Nicholls SJ, Wolski K, Nesto R, Kupfer S, Perez A
(2008). PERISCOPE Investigators. Comparison of
pioglitazone vs glimepiride on progression of coronary
atherosclerosis in patients with type 2 diabetes: the
PERISCOPE randomized controlled trial. JAMA. 299:
1561-73.
Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S,
Motoyoshi S (1995). Intensive insulin therapy prevents
the progression of diabetic microvascular complications
in Japanese patients with non-insulin-dependent diabetes
mellitus: a randomized prospective 6-year study.
Diabetes Res. Clin. Pract., 28:103-17.
Patel A, MacMahon S, Chalmers J, Neal B, Billot L
(2008). Intensive blood glucose control and vascular
outcomes in patients with type 2 diabetes. N Engl J
Med.358: 2560-72.
Rockville, MD (2007). Guide for Conducting Comparative
Effectiveness Reviews.; Agency for Healthcare Research
and Quality.
Rodbard HW, Jellinger PS, Davidson JA, Einhorn D, Garber
AJ, Grunberger G (2009). Statement by an American
Association of Clinical Endocrinologists/American
College of Endocrinology consensus panel on type 2
diabetes mellitus: an algorithm for glycemic control.
Endocr Pract. 15: 540-59.

20

Shichiri M, Kishikawa H, Ohkubo Y, Wake N 2000. Longterm results of the Kumamoto Study on optimal diabetes
control in type 2 diabetic patients. Diabetes Care. 23
Suppl 2:B21-9.
Temple R, Ellenberg SS (2000). Placebo-controlled trials and
active-control trials in the evaluation of new treatments.
Part 1: ethical and scientific issues. Ann Intern Med. 133:
455-63.
UK prospective diabetes study (1985). II. Reduction in HbA1c
with basal insulin supplement, sulfonylurea, or biguanide
therapy in maturity-onset diabetes. A multicenter study.
Diabetes.34:793-8.
UK Prospective Diabetes Study (UKPDS) Group. Lancet.
(1998). Effect of intensive blood-glucose control with
metformin on complications in overweight patients with
type 2 diabetes (UKPDS 34). 352:854-65.
UK Prospective Diabetes Study (UKPDS) Group. Lancet.
(1998).
Intensive
blood-glucose
control
with
sulphonylureas or insulin compared with conventional
treatment and risk of complications in patients with type
2 diabetes (UKPDS 33). 352:837-53.
United Kingdom Prospective Diabetes Study 24 (1998). A 6year,
randomized,
controlled
trial
comparing
sulfonylurea, insulin, and metformin therapy in patients
with newly diagnosed type 2 diabetes that could not be
controlled with diet therapy. United Kingdom
Prospective Diabetes Study Group. Ann Intern Med.
128:165-75.
United Kingdom Prospective Diabetes Study (1998) 24: a 6year,
randomized,
controlled
trial
comparing
sulfonylurea, insulin, and metformin therapy in patients
with newly diagnosed type 2 diabetes that could not be
controlled with diet therapy. United Kingdom
Prospective Diabetes Study Group. Ann Intern Med.
128:165-75.
United Kingdom Prospective Diabetes Study (UKPDS) (1995)
13: Relative efficacy of randomly allocated diet,
sulphonylurea, insulin, or metformin in patients with
newly diagnosed non-insulin dependent diabetes
followed for three years. BMJ. 1995;310:83-8.

J. Med. Sci. Adv., 2012, 1(1):17-20