Title: Glyburide, Gliclazide or Glimepiride in the Elderly
Date: 18 April, 2007
Context and policy issues:
Type 2 diabetes is characterized by chronically elevated blood sugar levels and
disturbances in carbohydrate, fat and protein metabolism.1 In 1998, the estimated
prevalence of diabetes in Canada for those aged 65 and over was approximately
15.09% or 576,398 people.2 Older individuals with diabetes have higher rates of
premature death, functional disability, and coexisting illnesses such as hypertension,
coronary heart disease, and stroke than age-matched individuals without diabetes.3,4
They are also at increased risk for several common geriatric problems such as
depression, cognitive impairment, urinary incontinence, injurious falls, and persistent
pain.3,4 A lower glycosylated hemoglobin (HBA1c) indicates better control of blood sugar
and is one of the treatment goals for diabetes. Data from uncontrolled studies suggest
that improved glycemic control is effective for preventing long-term complications from
diabetes in the elderly,5 although there is no evidence from controlled studies to
supports this. While there are a number of evidence-base guidelines for diabetes, few
guidelines3,4,6 are specifically targeted toward the control of diabetes and its associated
risk factors in elderly people.
Sulfonylureas (SU) are the oldest class of oral hypoglycemic agents available for the
treatment of type 2 diabetes.7 While they are moderately effective at lowering blood
glucose concentrations by 20% and HbA1c by 1-2%, their effectiveness is known to
decrease over time.7 SU primarily work by stimulating insulin release from pancreatic
beta cells, but may also reduce glucose output from the liver and increase insulin
sensitivity at peripheral target sites.7-10 Second generation SU available in Canada
include glyburide (also known as glibenclamide), gliclazide, and glimepiride.11 Second
generation SU are favored over the first generation SU, chlorpropamide, due to lower
Disclaimer: The Health Technology Inquiry Service (HTIS) is an information service for those involved in planning and providing health care in
Canada. HTIS responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of
sources and a summary of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. HTIS
responses should be considered along with other types of information and health care considerations. The information included in this response is
not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health
technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the
case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While
CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make
any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report.
Copyright: This report contains CADTH copyright material. It may be copied and used for non-commercial purposes, provided that attribution
is given to CADTH.
Links: This report may contain links to other information on available on the websites of third parties on the Internet. CADTH does not have
control over the content of such sites. Use of third party sites is governed by the owners’ own terms and conditions.
risk of adverse effects including hypoglycemia.7 In Canada, the use of second
generation SU is increasing among elderly people using oral hypoglycemics to treat
type 2 diabetes. In Nova Scotia, the percentage of seniors using glyburide decreased
slightly from 68% in 1993 to 59% in 1999, while use of gliclazide increased dramatically
from 2% in 1993 to 22% in 1999.12 In Ontario, SU were the most commonly prescribed
oral hypoglycemic drug class in older type 2 diabetics in 2001, with a 25% increase in
the number of people using these drugs between 1995 and 2001.13 These figures are
partially explained by the lower cost of SU. The average annual cost to the Ontario Drug
Benefit Plan in 2001 for SU was $61.88/person compared with $108.99/person for
biguanides, $170.71/person for meglitinides, $169.44/person for alpha-glucosidase
inhibitors, $295.16/person for thiazolidinediones, and $373.09/person for insulin.13
In the elderly, susceptibility to hypoglycemia is pronounced and often complicated by
decreased cognition. Furthermore, diagnosis of hypoglycemia may be hampered by the
fact that the classical adrenergic signs of hypoglycemia (palpitation, sweating, tremors)
are often absent, and neuroglycopenic symptoms (drowsiness, delirium, and confusion)
may be easily misinterpreted as other geriatric syndromes.14,15 In addition to cerebral
damage, seizures, coma or death in the general population, prolonged hypoglycemia
may also provoke a myocardial infarction, atrial fibrillation, or stroke in the elderly.16
Overall, results from randomized controlled trials in the general adult population indicate
similar efficacy in terms of blood glucose control between glyburide, glimepiride, and
gliclazide 17-22 but lower rates of hypoglycemia associated with glimepiride and
gliclazide when compared with glyburide.17,18,22,23 It is important to ascertain whether
these findings extend to the elderly population in order to guide treatment in terms of
safety and efficacy. This report will provide a review of the evidence evaluating the use
of different sulfonylureas in elderly individuals with type 2 diabetes.
Research questions:
What is the clinical effectiveness in terms of blood glucose control for glyburide in
seniors with Type 2 diabetes? What is the clinical effectiveness of glyburide compared
with gliclazide, glimepiride, or other standard treatment in seniors with Type 2 diabetes?
What is the cost-effectiveness of glyburide in seniors with Type 2 diabetes? What is the
cost effectiveness of glyburide compared to gliclazide or glimepiride in seniors with
Type 2 diabetes?
Methods:
A limited literature search was conducted on key health technology assessment
resources, including PubMed, EMBASE, The Cochrane Library (Issue 1, 2007),
University of York Centre for Reviews and Dissemination (CRD) databases, ECRI’s
HTAIS, EuroScan, international HTA agencies, and a focused Internet search. Results
include articles published between 2002 and the present, and are limited to English
language publications only. Bibliographies of reports were scanned to identify other
relevant evidence.
Glyburide, Gliclazide or Glimepiride for Diabetes in the Elderly
2
Summary of findings:
The observed differences in hypoglycemic risk among the different SU may be
explained by variations in the pharmacological profile for each drug (Table1). Glyburide
and glimepiride are long-acting and the formation of active metabolites increases the
risk for prolonged hypoglycemia. Rapid and prolonged hypoglycemia of greater than 12
hours despite glucose injections have been reported with glyburide and glimepiride in
elderly patients.24, 25 This does not appear to be an issue with shorter-acting gliclazide
due to metabolism to inactive metabolites. Moreover, a gradual increase in gliclazide
plasma concentrations further reduces the risk for hypoglycemia when compared with
the sharp increase demonstrated with glimepiride and glyburide. There is evidence that
once daily dosing with the long-acting formulation of gliclazide MR significantly improves
both compliance and glycemic control when compared with twice daily glyburide.26
Table 1: Second Generation Sulfonylureas Available in Canada11,15,27-30
Drug
(Brand Name)*
Dose Range
(mg)†
Doses Per
Day
Peak Plasma Levels
(h)
Duration Of Action
(h)
Glyburide
(Diabeta®)
Gliclazide
(Diamicron®)
1.25-20
1-2
2-4
20-24+
40-320
1-2
4-6
12-24
Gliclazide MR
30-120
1
6-12
~24
(Diamicron MR®)
Glimepiride
1-8
1
2-3
24+
(Amaryl®)
* There are several generic products for each sulfonylurea, except modified-release (MR) gliclazide.
†
Starting dose is typically lower with a longer titration period to therapeutic dose for elderly patients
As the oldest second generation SU with many generic forms, glyburide is the cheapest
option, followed by gliclazide, then glimepiride. As there are currently no generic forms
available for gliclazide MR, it is currently the most expensive alternative.
No health technology assessments, systematic reviews, meta-analyses, or economic
evaluations addressed the use of SU in the elderly population. A few randomized
controlled studies of fair methodological quality have been conducted assessing the
safety and efficacy of SU in elderly patients. Details of these trials are provided in Table
2.
Tessier et al conducted a small trial (n=22) to compare the effect of glyburide and
gliclazide on the frequency of hypoglycemic events and glycemic control in elderly
patients.31 Results revealed that while both were similar for glycemic control after 6
months of treatment, the incidence of hypoglycemic episodes was significantly greater
with glyburide when compared with gliclazide. The authors did not comment on the
severity of hypoglycemic episodes (i.e. if intravenous administration of glucose was
required in any of the cases). Three participants in the glyburide group and one
Glyburide, Gliclazide or Glimepiride for Diabetes in the Elderly
3
participant in the gliclazide group required combination therapy with metformin to
achieve adequate glucose control. Only one of the hypoglycemic episodes occurred in
a participant who was being treated concurrently with glyburide and metformin; the
other episodes occurred in participants receiving glyburide or gliclazide alone. Majority
of the hypoglycemic episodes occurred within one month of initiating treatment with
either SU (13 of the 17 episodes in the glyburide group and all of the 4 episodes in the
gliclazide group).
Schernthaner et al conducted the first large-scale (n=842) head-to-head comparison of
two SU designed for once-daily administration (gliclazide MR versus glimepiride).21 A
subgroup analysis of participants over the age of 65 (n=294) revealed that changes in
HbA1c from baseline after 27 weeks were significant for each drug but did not differ
significantly between the two groups. In agreement with the study by Tessier et al.,
most hypoglycemic episodes in patients >75 years old, occurred soon after initiating
treatment (15 on 30-60 mg gliclazide MR out of 22 episodes, and 48 on glimepiride 1-2
mg out of 56 episodes). However, there was no significant difference in the occurrence
of hypoglycemic episodes between the two groups. The sample size for subgroup
analysis may not have been large enough to detect a significant difference. It is
important to note that when the total study population was analyzed, the difference was
significant (p=0.003) with 50% fewer confirmed hypoglycemic episodes reported with
gliclazide MR compared with glimepiride. Furthermore, the number of patients
experiencing hypoglycemia who were concurrently receiving metformin was also
significantly lower in patients receiving gliclazide MR in comparison to glimepiride
(p≤0.02). Interestingly, the difference between the two groups was not significant for
those concurrently receiving an alpha-glucosidase inhibitor or those receiving either SU
alone. Results for entire study population also revealed that even a mild impairment of
renal function (creatinine clearance <80 mL/min) significantly increased the incidence of
hypoglycemia with glimepiride but not with gliclazide MR (p≤0.02), an important result
when considering use in elderly patients with frequently reduced renal function.
Two open-label trials32,33 demonstrated significant improvements in glycemic control
after 16 weeks with Humalog Mix 75/25 compared with glyburide, and similar rates of
hypoglycemia. An open label cross-over trial (n=90) indicated a significant reduction in
hypoglycemic episodes when repaglinide was compared with glyburide.34 There was
also a significant improvement in blood glucose control with repaglinide when compared
with glyburide after 12 weeks of treatment.
Glyburide, Gliclazide or Glimepiride for Diabetes in the Elderly
4
Table 2: Summary of Evidence for Safety and Efficacy of Sulfonylureas in the
Elderly
Study
Design
Intervention
Results
Conclusions
Tessier et al.,
199431
Double-blind,
parallel group,
RCT
Glyburide
2.5-20 mg daily
vs.
Gliclazide
40-320 mg daily
HbA1c after 6 months
Glyburide; 7.4± 0.2%
Gliclazide: 7.9±0.5%
(p=NS)
Similar glycemic control
between glyburide and
gliclazide.
Inclusion age:
> 65 years old
(n=22)
6 months
Schernthaner
et al., 200421
Double-blind,
parallel group,
RCT
Inclusion age:
> 35 years old
(n=842)
>65y subgroup:
(n=294)
27 weeks
Both given as
monotherapy or in
combination w/
metformin 500 mg
three times daily
Hypoglycemic episodes:
Glyburide: 17 (4 patients)
Gliclazide: 4 (3 patients)
(p<0.01)
Incidence of hypoglycemic
episodes was significantly
greater with glyburide,
particularly during dose
titration.
Gliclazide MR
30-120 mg daily
vs.
Glimepiride
1-6 mg daily
For >65 y subgroup:
HbA1c after 27 weeks:
Gliclazide MR: 7.2±1.0%
Glimepiride: 7.2±1.1%
(p=NS)
Gliclazide MR is as effective
as glimepiride either as
monotherapy or in
combination.
Both given as
monotherapy or in
combination w/
metformin or
α-glucosidase
inhibitor (acarbose
or miglitol)
Change in HbA1c from baseline
after 27 weeks:
Gliclazide MR: -1.1±1.2%
Glimepiride: -0.9±1.0%
(within group: p<0.001)
Fewer hypoglycemic
episodes with gliclazide but
difference did not reach
significance.
Hypoglycemic episodes:
Gliclazide MR: 10 (5 patients)
Glimepiride: 17 (14 patients)
(p=NS)
No reports of severe
hypoglycemia requiring extra
treatment occurred.
Herz et al,
200232
Open-label,
parallel group,
RCT
Inclusion age:
60-80 years
(n=143)
16 weeks
Pre-mixed
Insulin Pen
(Humalog
Mix75/25)
Twice daily
injections
(0.3-0.5
units/kg/day)
vs.
Glyburide
15-20 mg daily
Glyburide, Gliclazide or Glimepiride for Diabetes in the Elderly
Change in HbA1c from baseline
after 16 weeks:
Mix75/25: -1.14±0.18%
Glyburide: -0.36±0.15%
(between group: p=0.001)
Hypoglycemia rate increase
(episodes/patient/30days):
Mix 75/25: 0.17±0.02
Glyburide: 0
(p=NS)
Compared with glyburide,
Mix 75/25 significantly
improved glycemic control in
older patients with type 2
diabetes, and could be
administered after meals
without compromising
glycemic control.
Rate of hypoglycemia
increase from baseline was
similar between the two
groups.
5
Study
Design
Intervention
Results
Conclusions
Gallic et al.,
200533
Open-label,
parallel group,
RCT
Pre-mixed
Insulin Pen
(Humalog
Mix75/25)
Twice daily
injections
(0.3-0.5
units/kg/day)
vs.
Glyburide
15 mg daily
Change in HbA1c from baseline
after 16 weeks:
Mix75/25: -1.45±1.58%
Glyburide: -0.60±1.48%
(between group: p=0.004)
Mix 75/25 significantly
improved glycemic control in
older patients with type 2
diabetes when compared
with glyburide.
Hypoglycemia rate increase
(episodes/patient/30days):
Mix 75/25: 0.06±0.35
Glyburide: 0.01±0.03
(p=NS)
Administration before or after
meals did not affect glycemic
control.
Repaglinide
3-6 mg daily
vs.
Glyburide
5-10 mg daily
Change in HbA1c from baseline
after 12 weeks:
Repaglinide: -0.77±1.0%
Glyburide: -0.36±0.9%
(between group: p=0.008)
There was a significant
improvement glycemic
control with repaglinide when
compared with glyburide.
Inclusion age:
60-80 years
(n=73)
16 weeks
Papa et al.,
200634
Open-label,
cross-over
RCT
Inclusion age:
≥65 years
(n=90)
12 week
treatment
period for each
drug with
3 week titration
in between
Patients having at least one
hypoglycemic episode:
Repaglinide: 26.1%
Glyburide: 42.0%
(p=0.026)
Rate of hypoglycemia
increase from baseline was
similar between the two
groups.
Treatment with repaglinide
significantly reduces
hypoglycemic episodes when
compared with glyburide
Hypoglycemia rate
(episodes/patient/12 weeks):
Repaglinide: 0.38±0.84
Glyburide: 0.81±1.4
(p=0.002)
No severe hypoglycemic
episodes or adverse events
occurred.
RCT= Randomized controlled trial, NS=Non significant
Various population-based observational studies have provided valuable information
regarding the safety of different sulfonylureas in the elderly population. Shorr et al,
conducted a four-year retrospective study of 19,932 patients aged 65 years or older with
type 2 diabetes.35 The reported rates of serious hypoglycemia (resulting in
hospitalization, emergency room admission or death) were over 2-fold higher in insulin
users than in patients using sulfonylureas.35 In addition, the authors reported that a
recent hospitalization was the strongest predictor for the development of hypoglycemia
in elderly patients. Other independent risk factors for the development of hypoglycemia
were advanced age, black race, and the concomitant use of five or more medications.35
When the authors compared the incidence of severe hypoglycemia with glyburide,
tolbutamide, tolazamide, chlorpropamide, and glipizide, they reported the highest
incidence in those patients taking glyburide and lowest incidence among those taking
Glyburide, Gliclazide or Glimepiride for Diabetes in the Elderly
6
tolbutamide.36 The incidence of severe hypoglycemia with chlorpropamide was similar
to that with glyburide while shorter-acting drugs such as tolazamide and glipizide were
associated with a lower incidence.36
Holstein et al conducted a prospective observational study to compare the incidence of
severe hypoglycemia in elderly patients treated with glyburide or glimepiride by
randomly selecting 400 doctors working in acute care hospitals in Germany to fill out a
standardized questionnaire.24 Over the course of 14 months, the number of reported
severe hypoglycemic episodes (requiring intravenous glucose) was much higher in
those treated with glyburide than in those treated with glimepiride (56 versus 37,
respectively; p value not reported). Prolonged hypoglycemia (requiring more than 12
hours of intravenous glucose administration) did not differ significantly between the two
groups (8 for glimepiride versus 5 with glyburide; p=0.126). Of the 13 patients with
prolonged hypoglycemia, renal impairment was present in 11 and hepatic dysfunction in
1. The authors concluded that the risk for severe hypoglycemia was just as great in
elderly patients treated with glimepiride as those treated with glyburide.24
During a two-year population survey of type 2 diabetic patients aged 80 years or older,
Angilieri et al. reported that out of a total of 1430 medical admissions due to diabetes,
25% were attributable to severe hypoglycemia requiring treatment with intravenous
glucose.25 Majority (68%) of the patients demonstrated prolonged hypoglycemia
occurring over a 12-72 hour duration. Among the patients hospitalized for
hypoglycemia, more were receiving treatment with SU than insulin (81% versus 19%).
Of the SU-related hypoglycemic episodes, 56% occurred in patients receiving glyburide
monotherapy (10-15 mg/day), 32% in patients taking glyburide in combination with
metformin, 4% in patients receiving combination therapy with acarbose, 4% receiving
gliclazide monotherapy, and 4% receiving gliquidone monotherapy. While the patients
were found to have an average HbA1c value of 5.1±0.6% (indicating that diabetes was
very well controlled), they also had marked co-morbidities (mostly cardiovascular).
These results suggest that when considering therapy and treatment goals for diabetes
in the elderly, it is important to consider risk for hypoglycemia and co-morbidities.25
Additional well-designed trials incorporating an economic component are required to
confirm the benefit and cost-effectiveness of gliclazide or glimepiride over glyburide in
elderly individuals with type 2 diabetes as well as assess efficacy in comparison to other
classes of oral hypoglycemics or insulin.
Conclusions and implications for decision or policy making:
In the general adult population, the choice of sulfonylurea is primarily dependent upon
cost and availability, as efficacy appears to be similar across the class.7 However, given
the increased risk and sequelae of hypoglycemia in the elderly, choice of drug should
be considered carefully. Due to the paucity of high quality evidence for this patient
population, the decision is often based on clinical experience. Guidelines developed by
the Canadian Diabetes Association recommend gliclazide and glimepiride should be
used over glyburide in elderly type 2 diabetics.37 The European Union Geriatric Society
Glyburide, Gliclazide or Glimepiride for Diabetes in the Elderly
7
guidelines recommend that where the risk of hypoglycemia is considered moderate
(renal impairment, recent hospital admission) to high (previous history of hypoglycemia,
frail patient with multiple co-morbidities, resident of a care home), gliclazide should be
considered over glyburide and glimepiride.4 When switching between different SU or
starting combination therapy with other oral hypoglycemics or insulin, it is important to
carefully monitor for signs and symptoms of hypoglycemia.38 Therefore, in order to avoid
severe hypoglycemia in elderly patients, target glycemic goals should be defined
critically with an appreciation for risk factors for hypoglycemia, co-morbidities, quality of
life, and life expectancy.
Prepared by:
Sarah Ndegwa, BScPharm, Research Officer
Melissa Severn MISt, Information Specialist
Health Technology Inquiry Service
Email: htis@cadth.ca
Tel: 1-866-898-8439
Glyburide, Gliclazide or Glimepiride for Diabetes in the Elderly
8
References:
1. Feig DS, Palda VA, Lipscombe LL, Canadian Task Force on Preventive Health
Care. Screening for type 2 diabetes to prevent vascular complications: updated
recommendations from the Canadian Task Force on Preventive Health Care
[Technical report]. London (ON): Canadian Task Force on Preventive Health Care;
2003. Available: http://www.ctfphc.org/Full_Text/CTF_DM_TR_final_2005.pdf
(accessed 2007 Apr 18).
2. Dawson KG, Gomes D, Gerstein H, Blanchard JF, Kahler KH. The economic cost
of diabetes in Canada, 1998. Diabetes Care 2002;25(8):1303-7. Available:
http://care.diabetesjournals.org/cgi/reprint/25/8/1303.pdf (accessed 2007 Apr 18).
3. Brown AF, Mangione CM, Saliba D, Sarkisian CA. Guidelines for improving the
care of the older person with diabetes mellitus. J Am Geriatr Soc 2003;51(5 Suppl
Guidelines):S265-S280.
4. European Diabetes Working Party for Older People 2001-2004. Clinical guidelines
for type 2 diabetes mellitus. 2004. Available:
http://www.eugms.org/documents/clinicalguidelinediabetes.pdf . (accessed 2007
Apr 18).
5. Katakura M, Naka M, Kondo T, Nishii N, Komatsu M, Sato Y, et al. Prospective
analysis of mortality, morbidity, and risk factors in elderly diabetic subjects: Nagano
study. Diabetes Care 2003;26(3):638-44.
6. American Medical Directors Association (AMDA). Managing diabetes in the longterm care setting. Columbia (MD): The Association; 2002. Available:
http://www.guideline.gov/summary/pdf.aspx?doc_id=3722&stat=1&string=glyburid
e+or+gliclazide+or+glimepiride (accessed 2007 Apr 18).
7. Sulfonylureas and megalitinides in the treatment of diabetes mellitus. In:
UpToDate [database online]. Version 15.1. Waltham (MD): UpToDate; 2007.
8. Glyburide drug information. In: UpToDate [database online]. Version 15.1.
Waltham (MD): UpToDate; 2007.
9. Glimepiride drug information. In: UpToDate [database online]. Version 15.1.
Waltham (MD): UpToDate; 2007.
10. Gliclazide drug information. In: UpToDate [database online]. Version 15.1.
Waltham (MA): UpToDate; 2007.
11. Sulfonylureas. In: e-CPS [database online]. Ottawa: Canadian Pharmacists
Association; 2007.
Glyburide, Gliclazide or Glimepiride for Diabetes in the Elderly
9
12. Morningstar BA, Sketris IS, Kephart GC, Sclar DA. Trends in oral
antihyperglycemic and insulin use in the Nova Scotia senior population (19931999). Can J Clin Pharmacol 2002;9(3):123-9.
13. Shah BR, Mamdani M, Kopp A. Drug use in older people with diabetes. In: Hux JE,
Booth GL, Slaughter PM, Laupacis A, editors. Diabetes in Ontario: an ICES
practice atlas. Toronto: Institute for Clinical Evaluative Sciences; 2003. p.3.
Available: http://www.ices.on.ca/WebBuild/site/ices-internetupload/file_collection/DM%5FChapter3%2Epdf. (accessed 2007 Apr 18).
14. Meneilly GS. Diabetes in the Elderly. Med Clin North Am 2006;90(5):909-23.
15. Oiknine R, Mooradian AD. Drug therapy of diabetes in the elderly. Biomed
Pharmacother 2003;57(5-6):231-9.
16. Holstein A, Plaschke A, Egberts EH. Clinical characterisation of severe
hypoglycaemia - A prospective population-based study. Exp Clin Endocrinol
Diabetes 2003;111(6):364-9.
17. Dills DG, Schneider J. Clinical evaluation of glimepiride versus glyburide in NIDDM
in a double-blind comparative study. Glimepiride/Glyburide Research Group. Horm
Metab Res 1996;28(9):426-9.
18. Draeger KE, Wernicke-Panten K, Lomp HJ, Schuler E, Rosskamp R. Long-term
treatment of type 2 diabetic patients with the new oral antidiabetic agent
glimepiride (Amaryl): a double-blind comparison with glibenclamide. Horm Metab
Res 1996;28(9):419-25.
19. Inukai K, Watanabe M, Nakashima Y, Sawa T, Takata N, Tanaka M, et al. Efficacy
of glimepiride in Japanese type 2 diabetic subjects. Diabetes Res Clin Pract
2005;68(3):250-7.
20. Drouin P, Diamicron MR once daily is effective and well tolerated in type 2
diabetes: a double-blind, randomized, multinational study. J Diabetes
Complications 2000;14(4):185-91.
21. Schernthaner G, Grimaldi A, Di MU, Drzewoski J, Kempler P, Kvapil M, et al.
GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride
in type 2 diabetic patients. Eur J Clin Invest 2004;34(8):535-42.
22. Charpentier G, Fleury F, Dubroca I, Vaur L, Clerson P. Electronic pill-boxes in the
evaluation of oral hypoglycemic agent compliance. Diabetes Metab
2005;31(2):189-95.
23. Harrower AD. Comparison of efficacy, secondary failure rate, and complications of
sulfonylureas. J Diabetes Complications 1994;8(4):201-3.
Glyburide, Gliclazide or Glimepiride for Diabetes in the Elderly
10
24. Holstein A, Plaschke A, Hammer C, Egberts EH. Characteristics and time course
of severe glimepiride- versus glibenclamide-induced hypoglycaemia. Eur J Clin
Pharmacol 2003;59(2):91-7.
25. Greco D, Angileri G. Drug-induced severe hypoglycaemia in type 2 diabetic
patients aged 80 years or older. Diabetes, Nutrition & Metabolism - Clinical &
Experimental 2004;17(1):23-6.
26. Kardas P. The DIACOM study (effect of Dosing frequency of oral Antidiabetic
agents on the compliance and biochemical control of type 2 diabetes). Diabetes
Obes Metab 2005;7(6):722-8.
27. Diamicron MR. In: e-CPS [database online]. Ottawa: Canadian Pharmacists
Association; 2007.
28. Diamicron. In: e-CPS [database online]. Ottawa: Canadian Pharmacists
Association; 2007.
29. Amaryl. In: e-CPS [database online]. Ottawa: Canadian Pharmacists Association;
2007.
30. Diabeta. In: e-CPS [database online]. Ottawa: Canadian Pharmacists Association;
2007.
31. Tessier D, Dawson K, Tétrault JP, Bravo G, Meneilly GS. Glibenclamide vs
gliclazide in type 2 diabetes of the elderly. Diabet Med 1994;11(10):974-80.
32. Herz M, Sun B, Milicevic Z, Erickson P, Fovenyi J, Grzywa M, et al. Comparative
efficacy of preprandial or postprandial Humalog Mix75/25 versus glyburide in
patients 60 to 80 years of age with type 2 diabetes mellitus. Clin Ther
2002;24(1):73-86.
33. Galic E, Vrtovec M, Bozikov V, Schwarzenhofer M, Milicevic Z. The impact of the
timing of Humalog Mix25 injections on blood glucose fluctuations in the
postprandial period in elderly patients with type 2 diabetes. Med Sci Monit
2005;11(12):I87-I92.
34. Papa G, Fedele V, Rizzo MR, Fioravanti M, Leotta C, Solerte SB, et al. Safety of
type 2 diabetes treatment with repaglinide compared with glibenclamide in elderly
people: a randomized, open-label, two-period, cross-over trial. Diabetes Care
2006;29(8):1918-20.
35. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Incidence and risk factors for serious
hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med
1997;157(15):1681-6.
36. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Individual sulfonylureas and serious
hypoglycemia in older people. J Am Geriatr Soc 1996;44(7):751-5.
Glyburide, Gliclazide or Glimepiride for Diabetes in the Elderly
11
37. Canadian Diabetes Association. 2003 clinical practice guidelines. Toronto: The
Association; 2003. Available: http://www.diabetes.ca/cpg2003/download.aspx
(accessed 2007 Apr 18).
38. Bell DS. Practical considerations and guidelines for dosing sulfonylureas as
monotherapy or combination therapy. Clin Ther 2004;26(11):1714-27.
Glyburide, Gliclazide or Glimepiride for Diabetes in the Elderly
12