philippine clinical practice guidelines for the diagnosis and management of type 2 diabetes mellitus
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A guideline suited for local realitiesTRANSCRIPT
Philippine Practice Guidelines for the Diagnosis & Management of
Type 2 Diabetes Mellitus
Iris Thiele Isip Tan MD, MSc, FPCP, FPSEMChief, Medical Informatics Unit
Associate Professor IV, UP College of Medicine
Adapted from the presentation of Dr. Cecilia Jimeno
Tuesday, April 23, 13
UNITE FOR DIABETES PHILIPPINESDiabetes Philippines
Institute for Studies on Diabetes Foundation, Inc.Philippine Society of Endocrinology & Metabolism
Philippine Center for Diabetes Education Foundation, Inc.
Tuesday, April 23, 13
Goals & Areas of Collaboration
Establishment of a national diabetes
database
Encourage best diabetes practices - development of a unified CPG
Spearhead the fight for patients’ rights & safety - vigilance on
false claims
UNITE FOR DIABETES PHILIPPINES
Tuesday, April 23, 13
Objectives for the Clinical Practice
Guideline
UNITE FOR DIABETES PHILIPPINES
To develop clinical practice guidelines on the screening, diagnosis and management of diabetes which reflect the current best evidence and
which incorporate local data into the recommendations, in view of aiding clinical decision making for the benefit of the
Filipino patient
GUIDELINES THAT ARE SUITED FOR LOCAL REALITIES
Tuesday, April 23, 13
Organizations in the Consensus Panel
Diabetes PhilippinesInstitute for Studies on Diabetes Foundation, Inc.Philippine Society of Endocrinology & Metabolism
Philippine Center for Diabetes Education Foundation, Inc.
23 other specialty, subspecialty organizationslay representatives of persons with diabetes
UNITE FOR DIABETES PHILIPPINES
Tuesday, April 23, 13
Scope of the Philippine CPG development
Outpatient setting
Screening and diagnosisScreening for complications
Prevention and treatmentSpecial groups: GDM, elderly
Tuesday, April 23, 13
Philippine Clinical Practice Guideline for
Diabetes Mellitus
Part 1:SCREENING & DIAGNOSIS
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Statement 2.1 All individuals being seen at any physician’s
clinic or by any healthcare provider should be evaluated annually for risk factors
for type 2 diabetes. (Table 1) [Grade D, Level 5]
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Statement 2.2 Universal screening using laboratory
tests is NOT recommended as it would identify very few individuals who are at risk.
[Grade D, Level 5]
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Table 1. Demographic and Clinical Risk Factors for Type 2 Diabetes
Testing should be considered in all adults >40 years old.
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Consider earlier testing if with at least one other risk factor as follows:
•history of IGT or IFG•history of GDM or delivery of a baby weighing 8 lbs
or above•polycystic ovary syndrome (PCOS)•overweight (BMI >23 kg/m2) or obese (BMI >25
kg/m2)•waist circumference >80 cm (♀) and >90 cm (♂)
or waist-hip ratio (WHR) >1 (♂) and >0.85 (♀)
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Consider earlier testing if with at least one other risk factor as follows (con’t):
•first-degree relative with type 2 diabetes•sedentary lifestyle•hypertension (BP >140/90 mm Hg)•diagnosis or history of any vascular diseases including
stroke, peripheral arterial occlusive disease, coronary artery disease
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Consider earlier testing if with at least one other risk factor as follows (con’t):
•acanthosis nigricans•schizophrenia•serum HDL <35 mg/dL (0.9 mmol/L) and/or•serum triglycerides >250 mg/dL (2.82 mmol/L)
Tuesday, April 23, 13
Which of the following will you NOT screen for diabetes?
a.42/F on follow-up for hypertension
b.35/M consulting for cough
c.45/M with tuberculosis
d.28/F diagnosed with PCOS
Tuesday, April 23, 13
Why 40?Recommendation
from other guidelines
ADA2010
CDA2008
AACE2007 IDF 2005
All >45 y (B)
Earlier if BMI >25 kg/m2 and with >1 risk factor(s)
(B)
All > 40 y
Earlier if with risk factors
>30 y with risk factor
(B)
Target high risk people
by risk factor
assessment
Tuesday, April 23, 13
Why 40?NNHeS 2008
Age (y)Prevalence of Diabetes MellitusPrevalence of Diabetes MellitusPrevalence of Diabetes MellitusPrevalence of Diabetes Mellitus
Age (y) Based on FBSa
Based on 2h postprandial
glucose
Based on DM questionnaire
True Diabetes
20-29 0.4 0.4 0.5 0.930-39 3.2 1.1 1.4 3.8
40-49 5.7 3.9 4.2 8.250-59 9.0 5.0 8.1 13.060-69 9.1 5.9 9.5 15.9>70 4.4 5.5 7.1 11.8
Overall 4.8 3.0 4.0 7.2a Based on FBS >125 mg/dLb Based on 2h-PPG > 200 mg/dLc Based on DM questionnaire (previous diagnosis by nurse or physician or on medication)d True diabetes (positive in any of the three assessment methods
Tuesday, April 23, 13
You screen the 42 y.o. hypertensive. FBS is 5.2 mmol/L. What next?
a.Reassure patient she is not diabetic. There is no need to repeat the test.
b.Repeat FBS after 1 year.
c.Order an OGTT after 6 months.
d.Ask for an HbA1c after 3 months.
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If initial test(s) are negative, when should repeat testing be done?
Repeat testing should ideally be done annually for Filipinos with risk factors owing to the significant prevalence and burden of diabetes in our
country. (Level 5, Grade D)
Tuesday, April 23, 13
CANDI ManilaFojas MC, Lantion-Ang FL, Jimeno CA, Santiago D, Arroyo M, Laurel A, Sy H, See J.
Complications and cardiovascular risk factors among newly-diagnosed type 2 diabetics in Manila. Phil. J. Internal Medicine, 47: 99-105, May-June, 2009
Local study: newly-diagnosed diabetics in Manila20% peripheral neuropathy
42% proteinuria2% diabetic retinopathy
COMPLICATIONS FOUND AT DIAGNOSIS!
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UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Recommended tests for diagnosing diabetes:
•Fasting plasma glucose (FPG) - 8-14 hours•Random plasma glucose (RPG)•2-h plasma glucose in 75-g OGTT
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Criteria for diagnosis of diabetes (Level 2, Grade B)
•FPG >126 mg/dL (7.0 mmol/L)•Random plasma glucose >200 mg/dL (11.1 mmol/L)
in a patient with classic symptoms of hyperglycemia (weight loss, polyuria, polyphagia, polydipsia) or with signs and symptoms of hyperglycemic crisis
•2-h plasma glucose in 75-g OGTT >200 mg/dL (11.1 mmol/L)
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Fasting plasma glucose (FPG) is the preferred test due to its wide availability, lower cost and better reproducibility (Level 3, Grade B)
•If the FPG falls within the impaired fasting glucose range (5.6-6.9 mmol/L) then a 75-g OGTT is recommended (Level 3, Grade B)
•Symptomatic patients - random or FPG
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UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Among asymptomatic individuals with positive results, any of the three tests should be
repeated within two weeks for confirmation (Level 4, Grade C).
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Diabetes can be diagnosed when any of the three tests are positive in a symptomatic patient (weight loss, polyuria, polyphagia, polydipsia).
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
A 75-g OGTT is preferred as the first test for the following (Level 3, Grade B):
•Previous FBS showing IFG 100-125 mg/dL (5.6-6.9 mmol/L)
•Previous diagnosis of CVD (CAD, stroke, peripheral arteriovascular disease) or who are at high risk of CVD
•A diagnosis of Metabolic Syndrome
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
At the present time, we cannot recommend the routine use of the following tests in the diagnosis of diabetes (Level 3, Grade C):
•HbA1c•Capillary blood glucose•Fructosamine•Urinalysis (Level 3, Grade B)• Plasma insulin (Level 3, Grade B)
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
•HbA1c•Capillary blood glucose•Fructosamine•Urinalysis
Interpret an available result with caution and confirm with any of the three standard tests (Level 2, Grade B).
Tuesday, April 23, 13
Why NOT Hba1C?
Until standardization has been done in the Philippines, use HbA1c only as a tool for monitoring control among those with established DM.
•HbA1c not readily available in some areas•NGSP certification not easily verified in laboratories•Studies needed to determine effect of ethnicity
Tuesday, April 23, 13
You screen the 42 y.o. hypertensive. FBS is 5.2 mmol/L. What next?
a.Reassure patient she is not diabetic. There is no need to repeat the test.
b.Repeat FBS after 1 year.
c.Order an OGTT after 6 months.
d.Ask for an HbA1c after 3 months.
Tuesday, April 23, 13
Screen for risk factors for DM, prediabetes and MetS
Algorithm for Screening Diabetes Among Asymptomatic Individuals
Tuesday, April 23, 13
Screen for risk factors for DM, prediabetes and MetS
Algorithm for Screening Diabetes Among Asymptomatic Individuals
Risk factors (Table 1)
YES
Tuesday, April 23, 13
Screen for risk factors for DM, prediabetes and MetS
Algorithm for Screening Diabetes Among Asymptomatic Individuals
Risk factors (Table 1)
YES
Lab testing using FBS, RBS, OGTT (Fig 3)
YES
Tuesday, April 23, 13
Screen for risk factors for DM, prediabetes and MetS
Algorithm for Screening Diabetes Among Asymptomatic Individuals
Risk factors (Table 1)
YES
Lab testing using FBS, RBS, OGTT (Fig 3)
YES
Age >40 y
NO
YES
Tuesday, April 23, 13
Screen for risk factors for DM, prediabetes and MetS
Algorithm for Screening Diabetes Among Asymptomatic Individuals
Risk factors (Table 1)
YES
Lab testing using FBS, RBS, OGTT (Fig 3)
YES
Age >40 y
NO
YES
No further testing; re-evaluate annually
for risk factors
NO
Tuesday, April 23, 13
Age >40 yAge <40 y with risk factors for DM
No 3 P’s or weight loss (asymptomatic)
No known CAD, PAD, CVD, No MetS
Diagnosed CAD, PAD, CVD or with MetS
Symptomatic (polyuria, polydipsia, polyphagia,
weight loss)
Tuesday, April 23, 13
Age >40 yAge <40 y with risk factors for DM
No 3 P’s or weight loss (asymptomatic)
No known CAD, PAD, CVD, No MetS
Diagnosed CAD, PAD, CVD or with MetS
Symptomatic (polyuria, polydipsia, polyphagia,
weight loss)
Fasting plasma glucose
<100 mg/dL
100-125 mg/dL
>126 mg/dL
No diabetesRepeat testing
after 1 y
75-g OGTT
Diabetes
Tuesday, April 23, 13
Age >40 yAge <40 y with risk factors for DM
No 3 P’s or weight loss (asymptomatic)
No known CAD, PAD, CVD, No MetS
Diagnosed CAD, PAD, CVD or with MetS
Symptomatic (polyuria, polydipsia, polyphagia,
weight loss)
Fasting plasma glucose
<100 mg/dL
100-125 mg/dL
>126 mg/dL
No diabetesRepeat testing
after 1 y
75-g OGTT
Diabetes
75-g oral glucose tolerance test
(OGTT)
FBS <100 & 2h <140 mg/dL
FBS 100-125
or 2h 140-199mg/dL
FBS >126 mg/dL or 2h >200
No diabetesRepeat testing
after 1 y
IFG or IGT
Repeat after 6
mosDiabetes
Tuesday, April 23, 13
Age >40 yAge <40 y with risk factors for DM
No 3 P’s or weight loss (asymptomatic)
No known CAD, PAD, CVD, No MetS
Diagnosed CAD, PAD, CVD or with MetS
Symptomatic (polyuria, polydipsia, polyphagia,
weight loss)
Fasting plasma glucose
<100 mg/dL
100-125 mg/dL
>126 mg/dL
No diabetesRepeat testing
after 1 y
75-g OGTT
Diabetes
75-g oral glucose tolerance test
(OGTT)
FBS <100 & 2h <140 mg/dL
FBS 100-125
or 2h 140-199mg/dL
FBS >126 mg/dL or 2h >200
No diabetesRepeat testing
after 1 y
IFG or IGT
Repeat after 6
mosDiabetes
Random plasma glucose
<140 mg/dL
140-199 mg/dL
>200 mg/dL
No diabetesRepeat testing
after 1 y
75-g OGTT
Diabetes
Tuesday, April 23, 13
Philippine Clinical Practice Guideline for
Diabetes Mellitus
Part 2:MANAGEMENT & MONITORING
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Initial evaluation - comprehensive medical history and PE
•Coronary heart disease risk assessment•Foot evaluation: assess risk for foot ulcer (identify
high-risk feet)•Eye exam: fundoscopy on diagnosis•Dental history or oral health history
Tuesday, April 23, 13
RED FLAGSof dental disease
tooth achepain when chewing
sensitivity to cold/hot drinks
badly broken teethswelling of gums
bad breath
Tuesday, April 23, 13
Prevalence among T2DM 68% (SLMC, n =192)
Bitong et al PJIM 2010
PERIODONTITIS
gum bleeding on brushingswelling and
redness of gumslooseness or
mobility of teethteeth that fall
off in adults
Tuesday, April 23, 13
Which of the following will you NOT request as initial tests for a person with diabetes?
a.Fasting blood glucose, HbA1c
b.Complete lipid profile
c.Blood uric acid, 12-lead ECG
d.ALT, AST, serum creatinine
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Minimal initial tests to be requested
• Fasting blood glucose, complete lipid profile• HbA1c• Liver function tests• Urinalysis; spot urine albumin-to-creatinine ratio• Serum creatinine and calculated GFR
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Optional tests
• ECG and TET• TSH in type 1 diabetes, dyslipidemia or women
over age 50 y
Tuesday, April 23, 13
Which of the following will you NOT request as initial tests for a person with diabetes?
a.Fasting blood glucose, HbA1c
b.Complete lipid profile
c.Blood uric acid, 12-lead ECG
d.ALT, AST, serum creatinine
Tuesday, April 23, 13
Which of the following statements is true about monitoring diabetes?
a. Monitor Hba1c ideally twice a year.
b. Check FBS and postprandial blood sugar every 2-4 weeks.
c. Estimate trends in blood sugar control by checking CBGs once a week.
d. Achieve glycemic goals within three months.
Tuesday, April 23, 13
Glycemic targets
Individualize targets.
FBS <4-7 mmol/L (72-126 mg/dL)
2h PPG <5-10 mmol/L (90-180 mg/dL)
Capillary (ADA) fasting 90-130 mg/dL
PPBG <180 mg/dL
HbA1c <7%
Tuesday, April 23, 13
Glycemic targets
Individualize targets.
FBS <6 mmol/L
2h PPG <8 mmol/L
Newly diagnosed Relatively young (age <60 y)
No complications No risk factors for hypoglycemia
HbA1c <6.5%
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Ideally, HbA1c every 3-6 months; 2x a year if controlled on stable therapy
FBS, postprandial sugar every 2-4 weeks
Capillary blood glucose 2x a week to estimate trends
Tuesday, April 23, 13
Glycemic targets should be achieved within 6 months of diagnosis or first prescription.
Tuesday, April 23, 13
Which of the following statements is true about monitoring diabetes?
a. Monitor Hba1c ideally twice a year.
b.Check FBS and postprandial blood sugar every 2-4 weeks.
c. Estimate trends in blood sugar control by checking CBGs once a week.
d. Achieve glycemic goals within three months.
Tuesday, April 23, 13
Targets to Decrease CV Risk
BP controlLipid control ASA
Tuesday, April 23, 13
Which of the following statements is true about reducing CV risk in diabetes?
a. Statins should be given regardless of baseline lipid levels.
b. There is insufficient evidence to recommend aspirin for primary prevention in men <60 y.
c. Give clopidogrel 75 mg/day for those with diabetes and a history of CVD.
d. The goal BP for most persons with diabetes is <140/80 mm Hg.
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
The goal BP for most persons with diabetes is <140/80 mm Hg.
•Lifestyle therapy alone for 3 months if pre-hypertensive (SBP 130-139 mm Hg or DBP 80-89 mm Hg)
•Pharmacologic + lifestyle therapy if SBP>140 mm Hg or DBP >90 mm Hg, or pre-hypertensive uncontrolled with lifestyle therapy alone
Tuesday, April 23, 13
Weight loss if overweightDASH-style dietary pattern
(reduce Na, increase K, moderation of alcohol,
increased physical activity).
Lifestyle therapy
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Statement 7.3 ACE inhibitors & ARBs are generally recommended
as initial therapy. If one class is not tolerated, the other should be substituted.
Multiple drug therapy (>2 agents at maximal doses) is generally required to achieve BP targets.
Thiazide-type diuretics, calcium channel blockers and B-blockers may be given as additional agents.
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Recommendations are consistent with Philippine Practice Guidelines for the Treatment of Dyslipidemia.
•LDL is the primary target for dyslipidemia management in persons with diabetes.
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Statement 8.1.1Statin therapy should be added to lifestyle therapy, regardless of baseline levels for diabetics
•with overt CVD (A)•without CVD who are >40 y and have >1more
other CVD risk factors (A)
Tuesday, April 23, 13
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Statement 8.1.2For patients at lower risk (e.g. without overt CVD and <40 y), statin therapy should be considered in addition to lifestyle therapy if -
•LDL-C remains >100 mg/dL•those with multiple risk factors (hypertension, familial
hypercholesterolemia, LVH, smoking, family history of premature CAD, male sex, age >55 y, proteinuria, albuminuria, BMI>25)
Tuesday, April 23, 13
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The 100-70 rule•Without overt CVD, goal is LDL-C <100 mg/
dL (2.6 mmol/L) [A]•With overt CVD, goal is LDL-C <70 mg/dL
(1.8 mmol/L). Use of high dose statin is an option. [B]
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Recommendation 9.2Insufficient evidence to recommend aspirin for primary prevention in lower risk individuals
•Men < 50 y•Women <60 y * Clinical judgement if with multiple risk factors
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Recommendation 9.3Use aspirin therapy for secondary prevention strategy in those with DM and a history of CVD [A].
•For patients with CVD and documented aspirin allergy, clopidogrel (75 mg/day) should be used.
Tuesday, April 23, 13
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Recommendation 9.4Combination therapy of ASA (75-162 mg/day) and clopidogrel (75 mg/day) is reasonable up to a year after an acute coronary syndrome [B].
Tuesday, April 23, 13
Which of the following statements is true about reducing CV risk in diabetes?
a. Statins should be given regardless of baseline lipid levels.
b. There is insufficient evidence to recommend aspirin for primary prevention in men <60 y.
c. Give clopidogrel 75 mg/day for those with diabetes and a history of CVD.
d.The goal BP for most persons with diabetes is <140/80 mm Hg.
Tuesday, April 23, 13
Newly diagnosed T2DM
Initiation of Drug Therapy among Newly Diagnosed Type 2 Diabetes Patients
Tuesday, April 23, 13
Newly diagnosed T2DM
Initiation of Drug Therapy among Newly Diagnosed Type 2 Diabetes Patients
HbA1c <9%FBS < 250
HbA1c >9%FBS > 250
Tuesday, April 23, 13
Newly diagnosed T2DM
Initiation of Drug Therapy among Newly Diagnosed Type 2 Diabetes Patients
HbA1c <9%FBS < 250
HbA1c >9%FBS > 250
Mono-therapy
Option for combination
therapy
Tuesday, April 23, 13
Newly diagnosed T2DM
Initiation of Drug Therapy among Newly Diagnosed Type 2 Diabetes Patients
HbA1c <9%FBS < 250
HbA1c >9%FBS > 250
Mono-therapy
Option for combination
therapy
Combination therapy
Insulin therapy
Tuesday, April 23, 13
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Statement 10.1Initiate treatment with metformin for monotherapy unless with contraindications or intolerance of its ADE’s -• diarrhea• severe nausea• abdominal pain
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
When optimization of therapy is needed, choose the second drug according to the following -
•degree of HbA1c lowering•hypoglycemia risk•weight gain•patient profile (dosing complexity, renal/hepatic
problems, other contraindications and age)
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Adapted from AACE Diabetes Mellitus Guidelines Endocr Pract 2007
Drug Therapy HbA1c reduction (%) MONOTHERAPYMONOTHERAPY
Sulfonylureas 0.9 to 2.5Biguanide (Metformin) 1.1 to 3.0Thiazolidinedione 1.5 to 1.6Alpha-glucosidase inhibitors 0.6 to 1.3DPP-4 inhibitors 0.8
NON-INSULIN INJECTABLENON-INSULIN INJECTABLEExenatide 0.8 to 0.9
COMBINATION THERAPYCOMBINATION THERAPYSU + Metformin 1.7SU + Pioglitazone 1.2SU + Acarbose 1.3Repaglinide + Metformin 1.4Pioglitazone + Metformin 0.7DPP-4 inhibitor + Metformin 0.7DPP-4 inhibitor + Pioglitazone 0.7
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Safety and Tolerability
Insulin secretagogues Metformin alpha-glucosidase
inhibitors TZDs Insulin
Risk of hypoglycemia ✔ ✔
Weight gain ✔ ✔ ✔GI side effects ✔ ✔Lactic acidosis ✔Edema ✔
1DeFronzo RA. Ann Intern Med 1999; 131:281–303. 2UKPDS. Lancet 1998; 352:837–853.3Nesto RW, et al. Circulation 2003; 108:2941–2948.
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Contraindications
Sulfonylurea Meglitinide Biguanide AGI TZD
Renal insufficiency ✔ ✔ ✔
Liver disease ✔ ✔ ✔ ✔ ✔Inflammatory bowel disease ✔
Congestive heart failure ✔ ✔
Known hypersensitivity ✔ ✔ ✔ ✔ ✔
Tuesday, April 23, 13
UNITE PHILIPPINE CPGFOR DIABETES MELLITUS
Since HbA1c reduction is the overriding goal, the precise combination used may not be as important as the glucose level achieved.
•There is no evidence that a specific combination is any more effective in lowering glucose levels or preventing complications than another.SU + Pio = SU + Metformin (Hanefield et al, 2004 & Nagasaka et al, 2004)
SU + Met = SU + DPP-IV inhibitors (?)
Tuesday, April 23, 13
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Statement 10.4.2The following patients must be referred to internists or diabetes specialists (endocrinologists or diabetologists) -• Type 1 diabetes• Moderate to severe hyperglycemia• Co-morbid conditions (infections, acute CV events i.e. CHF or
acute MI)• Significant hepatic and renal impairment• Women with diabetes who are pregnant
Tuesday, April 23, 13
Clinical practice guidelines aim to help physicians and patients reach the best healthcare decisions.
Steinbrook R. NEJM 2007
Tuesday, April 23, 13
“If you write it, and it is good, then they will follow.”
Keefer JH. Clin Chem 2001
Tuesday, April 23, 13
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