Management of Type 2 Diabetes Mellitus · Konsensus Pengelolaan dan Pencegahan Diabetes Melitus...
Transcript of Management of Type 2 Diabetes Mellitus · Konsensus Pengelolaan dan Pencegahan Diabetes Melitus...
Management of Type 2 Diabetes Mellitus
Name of Presenter:
SAID.GLI.18.04.0171(04/18)
What is Diabetes Mellitus ?
Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.
American Diabetes Association. Diabetes Care 2004 Jan; 27(suppl 1): s5-s10.
Number of people with diabetes worldwide and per region in 2017 and 2045 (20-79 years)
Amongst the 425 million people affected with diabetes in 2017, over 200 million come from Asia.
IDF-Diabetes Atlas 8-th eds-2017
IDF Diabetes Atlas, 8th Ed. 2017.
Top Ten Countries/Territories for Number of People with Diabetes (20-79 years)
Top Ten Countries for Number of IGT 2017 (20-79 years)
IDF Diabetes Atlas, 8th Ed. 2017.
Sumber : Riskesdas 2007
Sumber : Riskesdas 2013
Masalah DM di Indonesia Tahun 2007 - 2013
Prevalensi Diabetes Melitus Pada Penduduk Usia ≥ 15 Tahun Menurut Provinsi
di Indonesia Tahun 2013
(Sumber: Riskesdas, 2013)
3.7 3.6
3.4 3.3
3 3
2.8 2.7
2.3
2.5 2.5
2.3 2.3 2.2 2.2
2.1 2 2
1.9 1.9 1.8
1.6 1.6 1.6 1.5
1.3 1.3 1.2 1.2 1.2
1 1
0.8
2.1
0
0.5
1
1.5
2
2.5
3
3.5
4
Classification of Diabetes
Type 1 Diabetes
due to autoimmune β-cell destruction, usually leading to absolute insulin deficiency
Type 2 Diabetes
due to progressive loss of β-cell insulin secretion frequently on the background of insulin resistance
Gestational diabetes mellitus Diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation
Specific types of diabetes due to
other causes
monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young), diseases of the exocrine pancreas
Diabetes Care 2018;41(Suppl. 1):S13–S27 | DOI: 10.2337/dc18-S002
Diabetes Symptoms
Weight loss – event eating
more (type 1), Tingling, pain,
or numbness in the hands/feet
(type 2)
Urinating often
Blurry vision
Cuts/bruises that are slow to heal
Feeling very
hungry
Extreme fatigue
Feeling very
thirsty
Diabetes Symptoms [Internet]. American Diabetes Association. [cited 2018Apr12]. Available
from: http://www.diabetes.org/diabetes-basics/symptoms/
peripheral glucose uptake
hepatic glucose production
pancreatic insulin secretion
pancreatic glucagon secretion
gut carbohydrate delivery & absorption
incretin effect
HYPERGLYCEMIA
?
Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011
Multiple, Complex Pathophysiological
Abnormalities in T2DM
_
_
+ renal glucose excretion
Ramlo-Halsted & Edelman. Clinical Diabetes,2000;18:80–85
Natural History of Type 2 Diabetes
*IGT=impaired glucose tolerance
Normal
Altered
Glucose
Metabolism IGT* Diagnosis
of T2D
Progression
of T2D
Insulin
concentration
Insulin Resistance
-Cell Dysfunction
Fasting glucose
Microvascular disease
Macrovascular disease
Post-meal glucose
Diabetes Care 2018;41(Suppl. 1):S13–S27 | DOI: 10.2337/dc18-S002
•Urbanization and modernization • less walking, less biking, and less daily physical activity.
•Dietary factors •Higher fat and lower carbohydrate intake •Unhealthy trans fats and saturated fats
•White rice consumption
•Higher glycemic index (GI) than whole grains
• Smoking •Associated with higher abdominal fat and a 45% increased risk of developing
diabetes
• Environmental pollutants •Also increase risk of insulin resistance and diabetes.
• Sleep-disordered breathing and sleep deprivation • Increases risk of diabetes and poor glycemic control
•Chronic infections •H. Pylori, Hepatitis B virus, etc.
Ronald CW, et al. Ann NY Acad Sci, 2013.
Various Environmental Factors of Diabetes Development in Asian Population
Diagnosis and Goal of Treatment in Type 2 Diabetes
Kadar Tes Laboratorium Darah untuk Diagnosis Diabetes dan Prediabetes
Konsensus Perkeni 2015
Sasaran Pengendalian DM
Parameter Target
IMT (kg/m2) 18.5 - < 23
Tekanan darah sistolik (mmHg) <140
Tekanan darah diastolic (mmHg) <90
Glukosa darah preprandial kapiler (mg/dl) 80-130
Glukosa darah 1-2 jam PP kapiler (mg/dl) <180
HbA1c (%) < 7 (atau individual)
Kolesterol LDL (mg/dl) <100 (<70 bila risiko KV sangat tinggi)
Kolesterol HDL (mg/dl) Laki-laki: >40; Perempuan: >50
Trigliserida (mg/dl) <150
Konsensus Perkeni 2015
Keterangan: KV = Kardiovaskular, PP = Post prandial
Depicted are patient and disease factors used to determine optimal A1C targets (ADA, 2018)
ADA. Diabetes Care 2018;41(Suppl. 1):S55–S64 | DOI: 10.2337/dc18-S006
18
Adapted from: 1. International Diabetes Federation. Time to Act: Type 2 diabetes, the metabolic syndrome and cardiovascular disease in Europe. 2006. 2. International Diabetes Federation. Time to Act. 2001. 3. Seaguist ER. Diabetes 2010;59:4–6.
Major microvascular and macrovascular complications of diabetes
Sexual dysfunction
Peripheral sensory dysfunction
Coronary heart disease
Skin infection
Atherosclerosis
Gastro-intestinal and bladder dysfunction
Diabetic foot
Diabetic retinopathy
Diabetic nephropathy
Diabetic neuropathy
Cerebrovascular disease
Peripheral vascular disease
Coronary disease
Cognitive impairment3
Cardiac autonomic neuropathy
Microvascular1,2 Macrovascular1,2
UKPDS 35: Impact of increasing A1c on Cardiovascular Disease in T2DM
Fatal and non-fatal MI 14% rise in rise per 1% in A1c
Fatal and non-fatal stroke 12% rise in rise per 1% in A1c
Amputasi/death from PVD 43% rise in rise per 1% in A1c
Heart failure 16% rise in rise per 1% in A1c
Haza
rd R
atio
Haza
rd R
atio
A1c (%) A1c (%)
Stratton et al. UKPDS 35. BMJ 2000;321:405-412
Diabetic
retinopathy
Diabetic
nephropathy
Diabetic
neuropathy
Limb
amputation
• Coronary heart disease
• Ischaemic stroke
• Congestive heart failure
Aim of treatment: to prevent the complications of diabetes
Non-vascular complications: Cancer Infections Degenerative diseases Depression Cognitive disorders …
Adapted from Grobbee DE. Metabolism 2003; 52: 24–28.
* The most common cause of death in patients with diabetes
Guidelines of the Management of Type 2 Diabetes
Langkah-langkah penatalaksanaan
DM
1. edukasi
2. Terapi gizi
medik
3. Latihan
Jasmani
4. Intervensi
Farmakologis
Penatalaksanaan Diabetes Melitus
Perkeni. Konsensus Pengelolaan dan Pencegahan Diabetes Melitus Tipe 2 di Indonesia, 2015
Algorithm of type 2 diabetes management in Indonesia
Healthy Life Style Modification
HbA1C <7.5% HbA1C ≥7.5%
HbA1C >9.0%
Monotherapy* with one of
below
- Metformin
- GLP1 R-agonist
- DPP4-I
- AGI
- SGLT2-I *
- Thiazolidindione
- Sulfonylurea
- Glinide
Metf
orm
in o
r o
ther
firs
t line d
rug
2 s
eco
nd lin
e d
rugs
- GLP1 R-agonist
- DPP4-I
- Thiazolidindione
- SGLT2-I *
- Basal Insulin
- SU / Glinide
- Cholesevelam**
- Bromocriptin QR**
- AGI
- GLP1 R-agonist
- DPP4-I
- Thiazolidindione
- SGLT2-I *
- Basal insulin
- SU / Glinide
- Cholesevelam**
- Bromocriptin QR**
- AGIIf HbA1C is not
achieved in 3 months,
added second drug
(combination 2 drugs)
Combination 3 drugs
Notes:
* Registered drugs, it selection and usage is considered
based on benefit, adverse, and availability
** Cholesevelam is not yet available in Indonesia, and
Bromocriptin QR is generally used in pituitary tumor
Combination 3 drugs
Combination 2 drugs
Insulin ± other drugs
Clinical features (-) Clinical features (+)
Starts or intensification insulin
therapy
In 3 months,
HbA1C > 7%
+ Monotherapy in 3
months, HbA1C > 7%
Combination 2 drugs* with
different mechanism
If HbA1C is not
achieved in 3 months,
added third drug
(combination 3 drugs)
If HbA1C is not
achieved in 3 months,
started or intensified
insulin therapy
Metf
orm
in o
r oth
er
firs
t line d
rug
Indonesian Endocrine Society (Perkeni) Consensus 2015
Sulfonylurea – Focus on Glimepiride
• For decades, sulfonylureas (SUs) have been important drugs in the antidiabetic therapeutic.
• They have been used as monotherapy as well as
combination therapy. • Modern SUs, such as glimepiride are associated with
better safety profiles.
Kalra S, et al. Indian J Endocr Metab 2018;22:132-57
Sulfonilurea – mekanisme kerja
Sulfonilurea menstimulasi sekresi insulin oleh sel β pankreas
Sulfonilurea berikatan pada reseptor sel beta
Sel beta
Dinding sel
Peningkatan kadar kalsium intraseluler memicu lepasnya insulin
Insulin disekresi dalam darah
Kanal kalsium
Kanal kalium menutup
Kanal kalium
Hal ini menyebabkan kanal kalsium sel beta membuka, meningkatkan aliran kalsium ke dalam sel
Sulfonilurea
Reseptor SUR/KIR 6.2
Glimepiride : Unique Dual Mode of Action
26
Action on insulin
secretion
Action on insulin
resistance
Glimepiride + +
Conventional Sulfonylureas + -
Glinides + -
Biguanides - +
Glitazones - +
-Glucosidase Inhibitors - +
Henry. Endocrinol Metab Clin. 1997;26:553-573; Gitlin, et al. Ann Intern Med. 1998;129:36-38 Neuschwander-Tetri, et al. Ann Intern Med. 1998;129:38-41; Goldberg, et al. Diabetes Care 21:1897-1903
Medical Management of Type 2 Diabetes. 4th ed. Alexandria, Va: American Diabetes Association; 1998:1-139 Fonseca, et al. J Clin Endocrinol Metab. 1998;83:3169-3176; Bell & Hadden. Endocrinol Metab Clin. 1997;26:523-537
De Fronzo, et al. N Engl J Med. 1995;333:541-549; Bailey & Turner. N Engl J Med. 1996;334:574-579
Changes in A1c Observe with Oral Antihyperglycemic Therapy in subject with DM2
Kabadi UM et al. Manage Care 2004
Sonnenberg G.E. et al.: Short term comparision of once- versus twice-daily administration of glimepiride in patients with non-insulin-dependent diabetes mellitus. Ann Pharmacother. 1997;31:671-6
Glimepiride can control 24 hour blood glucose with once or twice daily administrations.
Placebo
3 mg glimepiride twice-a day (BID)
6 mg glimepiride once-a-day (QD)
350
300
250
200
150
0 2 4 6 8 10 12 14 16 18 20 22 24 hours
08.00 breakfast 12.00 Lunch
18.00 Dinner
Glimepiride – once or twice dosing
Blood glucose mg/dl
29
Korytkowski M et al. Diabetes Care 2002; 25(9):1607-11.
Insulin Secretion of Glimepiride
Glimepiride : Treat fasting AND postprandial hyperglycemia
First Phase Second Phase Insulin secretion
Before treatment After treatment
Incr
em
en
tal p
lasm
a in
sulin
(p
mo
l/L)
0
50
100
p=0.04
p=0.02
First and second phase insulin secretion
before and after treatment with Glimepiride
Euglycemic and hyperglycemic clamp studies in 11 obese patients with T2DM with good glycemic control before and after 4 months treatment with ®glimepiride to assess effect of glimepiride® on insulin secretion
Müller G et al. Diabetes Res Clin Pract 1995;28 (suppl):S115-S137
Comparison of Extrapancreatic Action of Glimepiride and Other Sulfonylureas
Mean plasma insulin increase (µU/ml) PI
Mean blood glucose decrease (%) BG
Glimepiride®
5 0 10 15 20
Su
lfo
nylu
rea
Glibenclamide
Gliclazide
Glipizide
PI/BG ratio
0.03 (n=16)
0.16 (n=16)
0.07 (n=14)
0.11 (n=13)
Sulfonylureas
tested in fasted
male beagle dogs
to determine
ratios of mean
plasma insulin
release/ blood
glucose decrease
Mean increase in plasma insulin (PI) and mean % decrease
in blood glucose (BG) over 6 hours after single dose
Glimepiride has better extrapancreatic activity among sulfonylureas
Holstein A et al. Diabetes Met Res Rev 2001; 17:467-73
Hypoglycemia vs Glibenclamide
*Defined as requiring IV glucose or glucagon
Significantly lower incidence of severe hypoglycemic events with Glimepiride vs glibenclamide (0.86 vs 5.6/1000 person-years)
0.86
5.6
Glibenclamide Glimepiride
# Ep
iso
des
/100
0 p
erso
n-y
ears
0
2
4
6
Prospective, population-based, 4-year study to compare frequency of severe hypoglycemia in patients with T2DM treated with Glimepiride (estimated n=1768) versus glibenclamide (estimated n=1721)
32
Weitgasser R et al. Diabetes Res Clin Pract 2003; 61: 13-19
Mean intra-individual weight change relative to baseline
-1.9 kg
(p<0.0001*)
-2.9 kg
(p<0.05*) -3.0 kg
(p<0.005*)
Months of treatment
Safety: Weight
Mean
weig
ht
ch
an
ge (
kg
)
*vs. baseline
4 12
- 1
- 2
- 3
18 0
Open, uncontrolled,
observational study.
1770 T2DM patients
were enrolled and 284
were followed-up for
1.5 years. Patients
received 0.5 to > 4 mg
glimepiride once daily.
Treatment with Glimepiride has a stable weight neutral or even weight reducing effect in most patients with Type 2 diabetes
Kejadian Hipoglikemia dan HbA1c sebelum, selama, dan setelah Ramadan
GLIRA Study Group Diabetes Care 2005; 28: 421
9.2
9
8
7
6
5
Pre-Ramadan During
Ramadan
7.7
Hb
A1
c (
%)
Post Ramadan
Period
7.1 7.3
7.7
8.4
Hypoglycemic
events : 25 (in 13
patients)
Hypoglycemic
events : 15 (in
11 patients)
Hypoglycemic
events : 8 (in 8
patients)
Newly diagnosed (n=100)
Already Treated (n=232)
Glimepiride tidak meningkatkan kejadian Hipoglikemia
Use of Glimepiride during Ramadan
Glimepiride bekerja selama
24 jam mengontrol gula
darah harian, cukup dikonsumsi
1x sehari
Panduan Penatalaksanaan DM Tipe 2 Pada Individu Dewasa di Bulan Ramadan, PERKENI 2015
Renal Impairment Dose Adjustment for insulin Compounds and oral medicines for Diabetes in CKD
National Kidney Foundation. Am J Kidney Dis. 2012; 60(5): 850-886
Cost
• SUs are associated with a significantly lower cost per QALYs and result in the longest time to insulin dependent1
• The cost comparison indicates that SUs would be the preferred as an add-on to metformin2
• Lower cost without compromising the glycemic efficacy and tolerability will make SUs the prime choice2
Lowers Costs
1Zhang Y, et al. Diabetes Care. 2014 May 1;37(5):1338-45 2Abrahamson MJ. Diabetes Care. 2015 Jan 1;38(1):166-9.
SUs incurs lower cost per QALY
81.75 54.85
232.84 325.97
245.7
0100200300400
Co
st p
er m
on
th(U
SD) Expected medication cost per QALY)
• Use of SU was associated with significantly lower cost per quality-adjusted
lifeyears (QALY) and resulted in the longest time to insulin dependent
Zhang Y, et al. Diabetes Care. 2014 May 1;37(5):1338-45
Take Home Message…….
• Diabetes can be managed by healthy lifestyle in combination with medical treatment
• Choosing the medication for patients should refer to doctor’s recommendation
• Early detection and treatment of diabetes can decrease the risk of developing the complications of diabetes
• Based on PERKENI guideline Glimepiride as an oral antidiabetic, can be initiated as monotherapy or combination with oral antidiabetics/ insulin/GLP-1 agonist in treating patients with newly diagnosed T2DM