Download SAFE n Smart* Use of Sulfonylureas

“SAFE & Smart”
Use of Sulfonylureas
• Practice Points for optimal use of this
essential class of drugs in T2DM
– Place of SU in current diabetes
management
– Addressing concerns with SU treatment
• Hypoglycemia, Weight changes,
Durability, CV risk, etc
– Choosing among the SUs
– Translating evidence into practice
• Patient selection, drug selection, dose
selection, patient empowerment &
physician empowerment
• Executive Summary released at the 2nd
SAFES Summit, Dhaka on 24 April, 2015
Kalra S, et al. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement. Indian J Endocrinol
Metab. 2015 Sep-Oct;19(5):577-96.
Situational Assessment…
Sulfonylureas In South Asia
• Majority of population in South Asia is treated with OHAs, either as
monotherapy or in combination.
• Both conventional and modern SUs remain the choice of OHA
prescription.
• Conventional SUs are listed alongside metformin, in the NLEM of
these nations
• Tolbutamide, one of the oldest SU, is still being prescribed in Sri
Lanka
• Recent studies from India/ Pakistan report SU+Metformin are more
efficacious than DPP4i+metformin combinations.
• During 2014, SUs (as combination therapy) constituted the majority
of OHAs market in India, with glimepiride combinations posting a
growth higher than the market
Kalra S, et al. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement. Indian J Endocrinol
Metab. 2015 Sep-Oct;19(5):577-96.
A: Indications of SUs
A1. SUs are an effective, safe, well tolerated, affordable & convenient therapeutic
option in the management of T2DM.
A2. SUs are effective second line agents after metformin, in the management of
T2DM. SU monotherapy as first line may be considered in Type 2 Diabetes with
metformin intolerance/ contraindication and in patients with MODY.
A3. Modern SUs should be initiated early in the course of T2DM, to achieve
maximum glycemic benefits and obtain the benefits of metabolic memory.
A4. SU- containing dual or triple FDCs, if available, (with drugs that have
complementary modes of action) reduce cost, offer convenience, and improve
patient adherence.
Kalra S, et al. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement. Indian J Endocrinol
Metab. 2015 Sep-Oct;19(5):577-96.
Place Of Sulfonylureas In Diabetes Therapy
Placement
Initial therapy
Approach
Monotherapy
2nd line therapy
Combination therapy with
metformin
Add on therapy
Subsequent add
on therapy
Special
consideration
Add on to combination
Indication
Contraindication to metformin
Intolerance to metformin
High blood glucose levels at presentation
Inadequate glycaemic control with metformin
Biological factors
Inadequate glycaemic control with existing
oral therapy
Age> 60
Psychosocial factors
Gluco-phenotype
Renal impairment
Neonatal diabetes
MODY-3
Ramadan*
Fasting hyperglycemia – prefer long-acting SUs
Post prandial hyperglycemia – prefer shortacting SUs
*preferred SUs include modern SUs like Glipizide MR, Gliclazide, Gliclazide MR, Glimepiride
Kalra S, et al. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement. Indian J Endocrinol Metab. 2015
Sep-Oct;19(5):577-96.
B. Preferred SUs
B1. Modern SUs should be preferred over conventional SUs in view of
the reduced mortality, better CV outcomes, and renal protection.
B2. Modern SUs should be preferred over conventional SUs in T2DM
patients at increased risk of hypoglycemia.
B3. Modern SUs should be the preferred choice of SU in
overweight/obese T2DM patients.
B4. Modern SUs should be preferred over conventional SUs in
patients at increased risk of CVD or with CVD.
Kalra S, et al. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement. Indian J Endocrinol
Metab. 2015 Sep-Oct;19(5):577-96.
C. SUs In Co-morbid Conditions
C1. Shorter acting drugs, especially those metabolized in the liver (glipizide), should
be the preferred SU in patients with moderate/severe renal impairment. In mild/
moderate renal impairment, gliclazide and glimepiride may also be used, preferably
at lower doses.
C2. Reduction of dose, and longer intervals between dose adjustments for SUs, are
recommended in patients with mild/moderate hepatic impairment.
C3. SUs with lower risk of hypoglycemia such as gliclazide MR and glimepiride are
recommended in elderly patients. Alternately, short acting SUs, or SUs in low dose
can be used.
C4. SUs are not indicated for use in children and adolescents, and should be
avoided in pregnancy & lactation
Kalra S, et al. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement. Indian J Endocrinol
Metab. 2015 Sep-Oct;19(5):577-96.
Strengths And Timing Of Administration Of SUs Including In Comorbidity
SUs
Strengths
Recommended dose
available (mg)
Dose Titration
Dose
Glipizide
IR: 5, 10
ER: 2.5, 5, 10
Before breakfast
Adult: 5 mg daily
Geriatric: 2.5 mg daily
Adult IR: 2.5-5 mg as frequently as No adjustment
every few days
Adult ER: adjustments no more
frequently than every 7 days
Geriatric IR: 2.5-5 mg every 1-2
weeks as needed
Geriatric ER: Conservative titration
Gliclazide
Tablet: 80
MR: 60
Adults: 40 mg daily in the
morning
MR: 30-120 mg at breakfast
With breakfast or first main meal
Adult: 2.5-5 mg daily
Adult Micro:1.5-3 mg daily
Geriatric: 1.25-2.5 mg daily
Renal Impairment
increased if necessary up to 320mg
(4 tablets) daily
> 160 mg: morning and evening
Glibenclamide Tablet: 1.25,
Adult: no more than 2.5 mg/day at
2.5, 5
weekly intervals
Micronized
Adult Micro: no more than 1.5
tablet: 1.25,
mg/day at weekly intervals
2.5, 5
Geriatric: 1.25-2.5 mg, 1-3 weeks
Glimepiride
1, 2, 4
With breakfast or first main meal Adult: 1-2 mg every 1-2 weeks as
Adult: 1-2 mg daily
needed
Geriatric: 1 mg daily
Geriatric: conservative titration
Renal: conservative titration
Glipizide +
2.5/250
With meals
As with individual agents
Metformin
2.5/500
As with individual agents
5/500
2.5-10/250-2000
Glibenclamide 1.25/250
With Meals
As with individual agents
+
2.5/500
As with individual agents
Metformin
5/500
1.25/250-20/2000
Glimepiride + 0.5/500,
Once daily with breakfast or first As with individual agents
Metformin
1/500, 1/850, main meal
2/500, 2/850, As with individual agents
3/850, 4/1000 1/500-2/500
Pioglitazone+ 30/2
Once daily with First main meal As with individual agents
Glimepiride
30/4
As with individual agents 30/2-4
15/1
Tablet and MR: Not
indicated in severe cases
Not recommended in CrCl
<50 mL/min
1 mg daily
As with individual agents
Hepatic Impairment
2.5 mg daily
Tablet and MR: Not
indicated in severe
cases
Avoid in severe
impairment
No adjustment needed
in minor.
Contraindicated in
severe impairment
As with individual
agents
As with individual agents
As with individual
agents
As with individual agents
As with individual
agents
As with individual agents
As with individual
agents
Kalra S, et al. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement. Indian J Endocrinol Metab. 2015 Sep-Oct;19(5):577-96.
D. SUs in Ramadan/Religious fasting
D1. SUs may be used during Ramadan, with appropriate counseling and dose
modification. Modern SUs are preferred as they confer lower risk of hypoglycemia.
D2. Individuals on once daily SU should take their medications at Iftar. The dose may
remain unchanged or reduced depending upon their pre-Ramadan glycemic status.
D3. Individuals on twice daily SUs, with higher doses in the morning and a smaller
dose in the evening, may shift the higher morning dose to Iftar, and the smaller
evening dose, or its half, to Suhur. The Suhur dose may be reduced further, if control
is adequate.
D4. Individuals with good control on conventional SUs do not require
major changes in drug regimen, except for dose titration.
Kalra S, et al. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement. Indian J Endocrinol
Metab. 2015 Sep-Oct;19(5):577-96.
E. Practical Tips For Using SUs
E1. Practice a ‘start low, step-up slow’ approach, up titrating gradually.
E2. SU titration should be based on glucose monitoring:
– once in two weeks –for responders with no hypoglycemia
– once a week –for non-responders, with or without hypoglycemia
E3. Timing of administration of SUs before the first, and subsequent major meals of
the day, is important. Importance of adherence must be explained.
E4. Patients/ family members should be educated on sick day management, need to
carry diabetes identity cards, recognition and management of hypoglycemia,
including de-escalation of SU doses, if required.
Kalra S, et al. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement. Indian J Endocrinol
Metab. 2015 Sep-Oct;19(5):577-96.
Practical Considerations For The Use Of
Sulfonylureas
Pragmatic Use of SUs
Posology
• Begin with low doses and up-titrate slowly, at weekly or fortnightly
intervals
• Avoid using more than half-maximal doses
Prescription
• SUs should ideally be used if one or two other drug classes fail to
achieve glycaemic targets
• Avoid using SUs in conjunction with another SU and/or premixed
or rapid acting insulin and/or meglinitides
• SUs can be prescribed as part of BIDS (bedtime insulin, day time
SU) regime
Adapted from: Kalra S and Gupta Y. Sulfonylureas. J Pak Med Assoc. 2015;65:101-4.
Practical Considerations For The Use Of
Sulfonylureas
Hypoglycaemia
• Educate the patient with diabetes, and their family members, about
hypoglycaemia
• Enquire about symptoms suggestive of hypoglycaemia at each visit
Lifestyle
• Advise a 3+3 meal pattern, especially with longer acting SUs
• Avoid physical activity during the time interval between SU administration and
meal intake and in the first few hours after SU ingestion
• Avoid missing meals
Weight
• Measure weight at every clinic visit
• Request the patient with diabetes to inform the physician in case of sudden,
unexplainable weight gain
Adapted from: Kalra S and Gupta Y. Sulfonylureas. J Pak Med Assoc. 2015;65:101-4.
Practical Considerations For The Use Of
Sulfonylureas
Pragmatic Use of SUs
Cardiovascular health
• Assess cardiovascular health prior to SU prescription
• Educate patients with diabetes, and family member, about
symptoms of angina
• Monitor cardiovascular health regularly
Fixed dose combination (FDCs)
• Prefer FDCs if available
• Prefer scored FDCs if available
• Empower the patient with diabetes to self-titrate the dose if
hypoglycaemia occurs
Adapted from: Kalra S and Gupta Y. Sulfonylureas. J Pak Med Assoc. 2015;65:101-4.
To Conclude…
• This initiative by SAFES aims to encourage rational, safe and smart prescription of
SUs
• Considering their efficacy, safety, pleiotropic benefits, and low cost of therapy, SUs
should be considered as recommended therapy for the treatment of diabetes in
South Asia.
• Modern SUs (glimepiride, gliclazide MR) are backed by a large body of evidence,
experience, and most importantly, outcome data, which supports their role in
managing patients with diabetes.
• Person-centred care, i.e., careful choice of SU, appropriate dosage, timing of
administration, and adequate patient counseling, will ensure that deserving
patients are not deprived of the advantages of this well-established class of antidiabetic agents
Kalra S, et al. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement. Indian J Endocrinol
Metab. 2015 Sep-Oct;19(5):577-96.
Thank You