RAKERDA & WEBINAR PD IAI KALIMANTAN BARAT, 11 DESEMBER 2021

TATALAKSANA TERAPI INSULIN PADA

PENDERITA DIABETES MELITUS

TRI MURTI ANDAYANI

Departemen Farmakologi dan Farmasi Klinik
Fakultas Farmasi UGM
trimurtia@ugm.ac.id
2

Pendahuluan

Tatalaksana terapi insulin

Outline
Inisiasi, titrasi, dan switching terapi
insulin

Penutup
PENDAHULUAN
 Definition

Diabetes is a group of metabolic disorders characterized by

chronic hyperglycemia associated with disturbances of
carbohydrate, fat, and protein metabolism due to absolute or
relative deficiency in insulin secretion and/or action

Diabetes causes long term damage, dysfunction &

failure of various organ
Patogenesis
 Type 1 DM → due to autoimmune b-cell destruction, usually leading to absolute insulin
deficiency

Type 2 DM → due to a progressive loss of adequate b-cell insulin secretion frequently on the
background of insulin resistance
classification

Gestational DM → diabetes diagnosed in the second or third trimester of pregnancy that was
not clearly overt diabetes prior to gestation

Specific types of DM → e.g.,monogenic diabetes syndromes (such as neonatal diabetes and

maturity-onset diabetes of the young), diseases of the exocrine pancreas (such as cystic fibrosis
and pancreatitis), and drug- or chemical-induced diabetes (such as with glucocorticoid use, in
the treatment of HIV/AIDS, or after organ transplantation)
 Fasting plasma glucose (FPG)
● Normal fasting glucose : 70-99 mg/dL
Definition of normal and
● Impaired fasting glucose : 100-125 mg/dL
abnormal glycemia
● Diabetes melitus : ≥ 126 mg/dL

2-hour post-load plasma glucose (oral glucose tolerance test)

● Normal glucose tolerance : < 140 mg/dL
● Impaired glucose tolerance : 140-199 mg/dL
● Diabetes melitus : ≥ 200 mg/dL

Glycosilated hemoglobin A1C (A1C)

● Normal A1C : 4% - 5,6%
● Increased risk of DM (Prediabetes) : 5,7% - 6,4%
● Diabetes melitus : ≥ 6,5%
Criteria for the diagnosis of DM
Goals of treatment

The primary goals of therapy for DM are to prevent or delay the

progression of long-term micro- and macrovascular
complications including retinopathy, neuropathy, diabetic kidney
disease, and ASCVD.
Additional goals of therapy are to alleviate symptoms of
hyperglycemia, minimize hypoglycemia and other adverse
effects, minimize treatment burden, and maintain quality of life.
 Glycemic target
recommendations in
various populations
Classification of hypoglycemia
TATALAKSANA TERAPI INSULIN
 Langkah-Langkah Penatalaksanaan DM

• TERAPI FARMAKOLOGIS
Edukasi → tingkat
awal dan tingkat lanjut • Obat antihiperglikemia oral
• Pemacu sekresi insulin (Sulfonilurea, glinid)
• Peningkat sensitivitas insulin (metformin,
tiazolidinedion)
Terapi nutrisi medis
• Penghambat alfa glucosidase (acarbose)
Terapi • Penghambat DPP-4 (vildagliptin, linagliptin,
Farmakologis sitagliptin, saxagliptin, alogliptin)
• Penghambat enzim sodium glucose co-
Latihan fisik transporter 2/SGLT-2 inhibitor

• Obat antihiperglikemia suntik

• Insulin
Terapi Farmakologis • Agonis GLP-1/Incretin mimetic (liraglutide,
exenatide, albiglutide, lixisenatide, dulaglutide)
INSULIN ● Carbohydrate metabolism → ↑ Transport of glucose inside
the cell, ↑ Peripheral utilization of glucose, ↑ Glycogen
synthesis, ↓ Glycogenolysis, ↓ Neoglucogenesis

● Lipid metabolism → ↓ Lypolisis, ↑ Lypogenesis, ↑

Glycerogenesis, ↓ Ketogenesis, ↑ Clearance of VLDL &
chylomicrons from blood through enzyme vascular
endothelial lipoprotein lipase

● Protein metabolism → Protein synthesis, ↑ Entry of amino

acids in cell
Pharmacodynamics of insulin
preparations
 Insulin
Common • Abdominal
When initiating insulin therapy sites of • Posterior upper arm
in someone with newly injection • Lateral thigh area
diagnosed type 1 DM, • Superior buttocks area
the starting dose is typically 0.4
to 1.0 units/kg/day of total
insulin.
The total daily dose of insulin is
then divided to give 50% as
basal insulin and 50% as
prandial insulin (distributed
across meals)
 Common insulin regimens.

(A) Multiple-component insulin

regimen consisting of one injection of
long-acting insulin (^detemir, glargine,
degludec) to provide basal glycemic
coverage and three injections of rapid
acting insulin (*aspart, lispro, glulisine) to
provide glycemic coverage for each meal.

(B) Insulin regimen consisting of two

injections of intermediate-acting
insulin (NPH) and rapid-acting insulin
(*aspart, lispro, glulisine [solid red line]),
or short-acting regular insulin (green
dashed line). Only one formulation of
short-acting insulin is used.
Indikasi pemberian insulin pada pasien
DM tipe 2
Indikasi pemberian insulin menurut
PERKENI
● HbA1c saat diperiksa ≥ 7,5% & sdh
menggunakan satu/2 obat
antidiabetes
● HbA1c saat diperiksa >9%
● Penurunan badan yg cepat
● Hiperglikemia berat disertai ketosis
● Krisis hiperglikemia
● Gagal dg kombinasi OHO dosis
optimal
● Stress berat (infeksi sistemik, operasi
besar, stroke. dll)
● Kehamilan dg DM/DM gestasional yg
tdk terkendali dg perencanaan makan
● Gg fungsi ginjal atau hati yg berat
● Kontraindikasi dan/atau alergi
terhadap OHO
● Kondisi perioperative sesuai indikasi
Algoritma Tatalaksana DM tipe 2

PERKENI 2019, Pedoman Pengelolaan & Pencegahan

DM tipe 2 dewasa di Indonesia
 Glucose-
lowering
medication in
type 2 diabetes
 Adding/
intensifying
insulin

AACE, 2019
Intensifying
to injectable
therapies
 Intensifying to
injectable therapies
Individualised antihyperglycaemic therapy in hospitalized patients with diabetes

Pasquel F., Lansang MC., Dhatariya K., Umpierrez GE. Management of diabetes and
hyperglycaemia in hospital. Lancet Diabetes Endocrinol. 2021;9:174-88
INISIASI, TITRASI DAN SWITCHING
TERAPI INSULIN
 PERMASALAHAN
TERKAIT PENGGUNAAN
INSULIN

Patient concerns
regarding initiating
injectable antidiabetic
therapy from patient &
endocrinologit
perspectives

Chen et el. 2020. The unmet medical needs of current

injectable therapies in China : Patient & health care
professional perspectives. Clinical Therapeutics. 42(8):1549-
1563
INISIASI DAN TITRASI INSULIN ?

● Pasien memahami alasan dan menyetujui diberikan insulin

● Memperagakan bagaimana menggunakan syringe/pen secara
beanr
● Pasien memahami pentingnya rotasi pemberian insulin
● Pasien memahami dosis, frekuensi dan injeksi insulin pada waktu
yg sama setiap hari
● Pasien perhatian terhadap penyimpanan & best before date
● Pasien mempunyai blood glucose meter & dpt menggunakan dgn
benar
● Pasien memahami gejala dan tanda hipoglikemia
● Penjelasan terkait peningkatan dan penurunan dosis insulin
● Pasien memahami target FPG & bagaimana penyesuaian dosis
● Perencanaan titrasi dosis antara dokter dan pasien
● Follow up jadwal konsultasi dengan dokter
 ADA-recommended
approach to initiating
& titrating insulin in
type 2 DM

Chun J., Strong J., Urquhart S. (2018)

Insulin initiation & titration in patients
with type 2 diabetes, Spectrum.
Diabetes Journals
 Titration algorithms
evaluated in clinical
trials

Chun J., Strong J., Urquhart S.

(2018) Insulin initiation &
titration in patients with type 2
diabetes, Spectrum. Diabetes
Journals
 • Switching Insulin ?

Alasan medik → efek

samping atau
episode hipoglikemia

Alasan praktis →
availabilitas obat,
cakupan asuransi,
kemudahan
pemberian dengan
metode penggunaan
yg baru

Alasan switching antar insulin basal

Perbandingan Efektivitas Insulin ? – Published systematic review & meta analysis
Published systematic review & meta analysis
Efikasi dan efek samping degludec dibandingkan glargine
Bagaimana switch antar insulin basal ?

Untuk meminimalkan risiko hiperglikemia & hipoglikemia → monitor kadar glukosa

darah lebih sering pada minggu pertama terapi & titrasi dosis insulin berdasarkan
standar terapi
Jika switching → edukasi pasien kemungkinan FPG tdk stabil & konsekuensi monitoring
lebih sering
Komunikasi dgn tim kesehatan → terkait aktivitas khusus yg perlu perhatian selama
periode waktu switching
 Mehta et al. 2021. Practical guidance on
the initiation, titration & switching of basal
insulins : a narrative review for primary
care, Annals of medicine 53(1):998-1009
 Initiation,
titration &
switching
instructions for
basal insulin
analoigs

Mehta et al. 2021. Practical guidance on

the initiation, titration & switching of basal
insulins : a narrative review for primary
care, Annals of medicine 53(1):998-1009
PENUTUP
 KESIMPULAN

● Terapi insulin mengikuti sekresi insulin fisiologis terdiri dari

sekresi basal dan sekresi prandial
● Terapi insulin untuk substitusi ditujukan untuk melakukan
koreksi terhadap defisiensi yang terjadi
● Pemilihan insulin harus memperhatikan invidualisasi serta
efektivitas obat, manfaat dan risiko hipoglikemia, harga dan
ketersediaan obat sesuai kebijakan.
● Inisiasi, titrasi, dan switching insulin disesuaikan dengan
kebutuhan pasien dan respons individu
Terima Kasih