Diabetes Research and Clinical Practice.

14 (199 1) S65-S68
0 1991 Elsevier Science Publishers B.V. 0168-8227/91/$03.50 S65

DIABET 00562

Efficacy of gliclazide in comparison with other sulphonylureas in

the treatment of NIDDM
A.D.B. Harrower

Monklands District General Hospital, Airdrie. U.K.

Summary

Three studies were performed to assess the efficacy of various sulphonylureas in the management of diet-
failed NIDDM patients. In the first study, 224 patients inadequately controlled by diet alone or with
oral hypoglycaemics received gliclazide in addition to diet or in place of existing drugs for three months.
The dosage was adjusted to obtain adequate control or up to the maximum recommended dosage. Good
glycaemic control was achieved in 65% of patients. Conversion from other oral hypoglycaemics to gliclazide
led to an improvement in control except in cases previously treated with glibenclamide. In the second
study, diabetic control was compared in 112 NIDDM patients treated concurrently for one year with
chlorpropamide, glipizide, gliquidone, glibenclamide or gliclazide. On the basis of HbA, levels, the best
results were obtained with glibenclamide and gliclazide, leading to normal HbAi levels in 74% and 80%
of patients, respectively. In the third study, secondary failure rates were assessed in 248 NIDDM patients
treated for five years with gliclazide, glibenclamide or glipizide. Gliclazide had the lowest secondary failure
rate (7%) and was significantly better than glipizide (25.6% failures in five years), but the difference relative
to glibenclamide (17.9%) just failed to reach the threshold of significance. The results of these studies
show that gliclazide is a potent hypoglycaemic agent which compares favourably with others of its type.
It has a low incidence of side effects, few problems with hypoglycaemia, and retains its efficacy longer
than other sulphonylureas. Gliclazide may therefore be considered a first choice for the therapy of diet-
failed NIDDM patients.

Key words: NIDDM; Treatment; Sulphonylureas

Introduction of therapy for diet-failed NIDDM. Although these

drugs have generally similar modes of action, there
With the introduction of new second generation are differences in metabolism. half-life, etc. [l],
sulphonylureas the clinician is faced with a choice which could be of clinical significance. The results
of some studies which have been carried out com-
Correspondence to: A. Harrower, Monklands District General paring different sulphonylureas will be presented.
Hospital, Airdrie ML6 OJS. U.K.
S66

Patients and Methods TABLE 1

Mean post-prandial blood glucose (PPBG) (mmol/l) on previous

Study 1 treatment and after treatment with gliclazide for three months
The efficacy of the sulphonylurea gliclazide was
Previous therapy Mean base- Mean PPBG after Signifi-
assessed in 224 NIDDM patients attending diabetic
line PPBG gliclazide for cance (P)
clinics in the U.K. [l]. After a four week run-in
(mmol/l) 3 months
period, patients inadequately controlled, either by (mmol/l)
diet alone (group 1: 106 patients), or by oral
hypoglycaemic agents (group 2: 118 patients), were Diet 12.3 8.3 <O.OOl
Chlorpropamide 14.3 9.4 <0.05
treated with gliclazide either in addition to diet or
Tolbutamide 11.7 7.1 <0.05
in place of existing drugs, and followed for three
Biguanides 13.7 9.5 <O.Ol
months. Dosage was adjusted until adequate con- Glibenclamide 13.2 13.0 N.S.
trol or the maximum recommended dosage was
reached.
achieved by transfer to gliclazide therapy except
Srudy 2 for patients previously treated with glibenclamide.
In a single diabetic clinic, diabetic control was There was also a mean weight loss for all patients
compared in 112 NIDDM patients treated concur- of 0.62 kg (P< 0.05).
rently for one year with five different sulphonyl-
ureas: chlorpropamide (21), glipizide (24), gliqui- Study 2
done (22), glibenclamide (23) and gliclazide (22) Table 2 shows the effect on HbAi levels after
[2]. The patients were reviewed regularly and the treatment with the different sulphonylureas. The
dosage adjusted, if necessary, to try and achieve best results were obtained with glibenclamide and
normal glycated haemoglobin (HbAi) levels. gliclazide. Only glibenclamide had any effect
on body weight, with a mean rise of 2.03 kg
Study 3 (P< 0.05).
A further study compared the secondary failure
rates in three second generation sulphonylureas, TABLE 2
gliclazide, glibenclamide and glipizide, in 248 Change in glycated haemoglobin (HbA,) and percentage of
NIDDM patients randomly allocated to one of patients achieving normal HbA, after treatment for one year
these drugs and followed for five years. A clinical with five different sulphonylureas

definition of secondary failure rate was used and

Sulphonylurea Mean change Signifi- Percentage of
patients who could not achieve post-prandial blood in HbA, (%) came (P) patients achieving
glucose (PPBG) levels below 10 mmol/l, or HbA, normal HbA, (%)
less than lo%, under supervised ward conditions
and after exclusion of any other significant medical Chlorpropamide + 0.7 N.S. 17
Glipizide + 0.6 N.S. 40
disorder were considered failures.
Gliquidone - 3.6 <O.Ol 40
Glibenclamide - 2.8 <O.O2 74
Gliclazide - 3.7 <O.Ol 80
Results

Study I Study 3
Table 1 shows the effect of gliclazide on mean PPBG Table 3 shows the secondary failure rate for each
levels in each group over the study period. Good drug after treatment for five years. Gliclazide had
control (PPBG<8 mmol/l) was achieved in 65% the lowest secondary failure rate and was signif-
of patients. In group 2 an improvement in PPBG was icantly better than glipizide. the difference with
 S67

TABLE 3 References
Percentage of secondary treatment failures after five years with
each of three sulphonylureas Ferner, R.F. and Chaplin, S. (1987)The relationship between
the pharmacokinetics and pharmacodynamic effects of oral
Sulphonylurea Failures after Significance hypoglycaemic drugs. Clin. Pharmacokinet. 12, 379-401.
five years Shaw, K.M., Wheeley, M.St.G., Campbell, D.B. and Ward,
(%) J.D. (1985) Home blood glucose monitoring in NIDDM:
the effect of gliclazide on blood glucose and weight control,
Gliclazide 7 a multicentre trial. Diabetic Med. 2,484-490.
N.S.
Glibenclamide 17.9 P<O.O05 Harrower, A.D.B. (1985) Comparison of diabetic control
N.S.
Glipizide 25.6 in type 2 (non-insulin dependent) diabetic patients treated
I
with different sulphonylureas. Curr. Med. Res. Opin. 9,676-
679.
Harrower, A.D.B. and Wang, C. (1990) Comparison of
glibenclamide just failing to reach significance
secondary failure rate between three second generation
(0.1 >P>O.O5). sulphonylureas. Diabetes Res. 13, 19-23.
Asplund, K.. Wilhelm. B.E. and Lithner. F. (1983) Gliben-
clamide associated hypoglycaemia: a report on 57 cases.
Discussion Diabetologia 24, 412-417.
Baba, S.. Nakagawa, S., Takebe, K. et al. (1983) Comparison
of gliclazide and glibenclamide treatment in NIDDM. To-
These reports, comparing gliclazide with other hoku J. Exp. Med. 141(Suppl.), 693-706.
sulphonylurea drugs, have indicated that gliclazide Campbell, I.W. (1983) Metformin and the sulphonylureas:
is a potent hypoglycaemic agent which compares the comparative risk. Horm. Metab. Res. lS(Suppl.), 105-
favourably with the other drugs studied. It has a 109.
Jennings, A.M., Wilson, R.M. and Ward. J.D. (1989)
low incidence of side effects and, perhaps because
Symptomatic hypoglycaemia in NIDDM patients treated
of its action in restoring a more physiological with oral hypoglycaemic agents. Diabetes Care 12,203-208.
insulin response from the P-cell [8], fewer problems Matthews, D., Hosker, J.M. and Turner, R. (1987) Effects
with hypoglycaemia than glibenclamide [6,7]. It of gliclazide on insulin secretion Induced by glucose and
also retains its efficacy longer than other sulphonyl- amino acids. Int. Diabetes Fed. Bull. 32. 12-15.

ureas.
In the choice of therapy for the diet-failed
NIDDM patient, gliclazide must be a serious first
choice contender.