Spesialits Obat Diabetes

Mellitus
Dewi Rahmawati
DEFINISI DIABETES MELLITUS
(DM) gangguan
metabolik
abnormalitas pd
metabolisme KH,
hiperglikemia
lemak dan
protein
menurunnya sekresi
insulin, sensitivitas
insulin atau bahkan
keduanya
 SULFONYLUREA
The first class of oral antidiabetic agents.
Increased pancreatic insulin secretion through
interaction with the sulfonylurea receptor on islet
cells.
Target pancreatic secretory dysfunction and raise
serum insulin levels high enough to overcome
insulin resistance in peripheral tissues.
Increased insulin levels flow directly into the portal
vein, decreasing hepatic glucose production
All members of this drug class appear to be equally
efficacious, with a decrease in fasting plasma
glucose concentration of about 60 to 70 mg/dL (3.3
to 3.9 mmol/L) and a drop in HbA1c levels of about
1.5% to 2% compared with placebo when maximal
doses are used
 Sulfonylurea
Can lead to hypoglycemia and
weight gain, particularly in elderly,
renal & liver disfunction
Unfortunately, as evidenced by the
UKPDS, most patients treated with
sulfonylurea monotherapy show a
progressive decline in blood glucose
control (17). It has been postulated
that this failure is due to
sulfonylurea-induced "exhaustion"
of beta cells
 Biguanide
Improve peripheral insulin
sensitivity, but it appears to exert
most of its effect on the liver i.e.
decrease hepatic glucose production
Problems with metformin include
several gastrointestinal distress
which prominent during initiation of
therapy.
Tends to induce modest weight loss
 Biguanide
The UKPDS revealed that the subgroup of overweight
patients taking metformin under the intensive protocol
had a reduction in microvascular risk similar to
sulfonylureas or insulin.
Greater reductions in all diabetes-related end points,
all-cause mortality rate, and stroke when compared
with the groups taking sulfonylureas or insulin.
The additional nonglycemic benefit of metformin may,
theoretically, be related to its insulin-lowering effect or,
more generally, to the improvement in insulin
resistance; both of these effects may directly or
indirectly attenuate the atherosclerotic process. Modest
beneficial effects on plasma lipids (24) and fibrinolysis
also have been demonstrated.
Studies have consistently shown that metformin also
lowers fasting plasma glucose levels by about 60 to 70
mg/dL (3.3 to 3.9 mmol/L) and HbA1c by about 1.5% to
2.0% (24).
It appears to be equally efficacious in non-obese
patients (24). It may, therefore, be an appropriate first-
Contraindications to metformin
therapy
Renal dysfunction
Serum creatinine level >1.5 mg/dL in men, >1.4
mg/dL in women
Metformin should be temporarily discontinued in
patients undergoing radiologic studies involving
intravascular administration of iodinated contrast
materials. Treatment may be restarted 48 hours after
the procedure when normal renal function is
documented.
Treatment should be carefully initiated in patients
>80 years of age after measurement of creatinine
clearance demonstrates that renal function is not
reduced.
Congestive heart failure that requires
pharmacologic therapy, or other form of acute or
chronic hemodynamic impairment
Hepatic dysfunction
Dehydration
Acute or chronic metabolic acidosis (including
 Alpha-glucosidase inhibitors

Retard the rate of absorption of carbohydrates through

the intestine by inhibiting the enzyme in the brush
border of enterocytes that cleave oligosaccharides to
monosaccharides.
Mild efficacy and the high frequency of gastrointestinal
distress
Suitable for patients with mild diabetes or those taking
other oral agents who continue to have large
postprandial blood glucose excursions.
Do not cause hypoglycemia when used as monotherapy,
and their use does not lead to weight gain.
Decrease postprandial plasma glucose levels by 40 to 60
mg/dL (2.2 to 3.3 mmol/L), fasting plasma glucose levels
by 20 to 30 mg/dL (1.1 to 1.7 mmol/L), and HbA1c levels
by 0.5% to 1.0% when compared with placebo
There are no long-term data on the protective effects
against diabetic complications.
 Thiazolidinediones

Increase insulin sensitivity in muscle and,

therefore, augment peripheral glucose disposal,
resulting in lower circulating glucose
concentrations
Exert most of its effect on peripheral skeletal
muscle, with relatively smaller effects on
hepatic glucose production (inverse to
metformin).
Concomitant use of metformin and troglitazone
has been found to be additive, providing further
support for the relatively distinct proposed
mechanisms of action.
Do not cause hypoglycemia when used as
monotherapy; however, their addition to
sulfonylureas, other secretagogues, or insulin
therapy can precipitate a hypoglycemic episode.
The currently available thiazolidinediones,
rosiglitazone maleate (Avandia) and
 Decrease fasting plasma glucose level of about 30 to
60 mg/dL (1.7 to 3.3 mmol/L) and a 1% to 1.5%
decrease in HbA1c level compared with placebo
Pioglitazone is given once daily and rosiglitazone
once or twice daily. Both agents have been shown to
lower serum free fatty acid levels and increase high-
density lipoprotein cholesterol levels.
Contraindicated in advanced forms of congestive
heart failure.
Augmenting insulin sensitivity, lowering insulin
levels, improving lipid profiles, and enhancing
fibrinolysis, the reduction in vascular disease with
thiazolidinediones might be expected to be larger
than with other agents (or at least as great as with
metformin).
 New Modalities in DM Treatment

Incretins are insulinotropic hormones secreted

from specialized neuroendocrine cells in the
small intestinal mucosa in response to
carbohydrate ingestion and absorption
The two hormones accounting for most incretin
effects are glucose-dependent insulinotropic
polypeptide (GIP) and glucagonlike peptide-1
(GLP-1).
 GIP and GLP-1 stimulate pancreatic -cells in a
glucose-dependent manner, contributing to the
early phase insulin response. GLP-1 also
inhibits pancreatic -cells, thus reducing
glucagon secretion and hepatic glucose
production. Incretin action is efficient, but short
lived
Adverse Effects: nausea, vomiting and/or
diarrhea, severe abdominal pain
Efficacy: menurunkan HbA1c : 0.8-1,0% pd 30
minggu, menurunkan BB 4-5kg pd 80 minggu
 New Modalities in DM
Treatment (cont.)
Exenatide
Exenatide is the only GLP-1 mimetic that is
approved by the FDA and is available as a sterile
solution for subcutaneous injection. has a half-life
of 12 to 14 hours, thus requiring twice daily
administration within 60 minutes prior to the
morning and evening meals.
Pharmacologic Effect: improve A1c values and
decreased weight,
Dose 2 x 10-mg,
The main adverse effect (AE) was nausea
 Nonsulfonylurea secretagogue

The mechanism of action of the

meglitinides, represented by repaglinide
(Prandin), is similar to that of the
sulfonylureas.
Unlike sulfonylureas, however,
meglitinides have a "quick on-quick off"
action that, theoretically, offers improved
postprandial control and reduces the
incidence of late postprandial
hypoglycemia
Taken shortly before each meal doses
ranging from 0.5 to 4 mg, up to three or
four times a day.
It may benefit patients with unpredictable
meal schedules or large postprandial
glucose excursions.
 Nonsulfonylurea
secretagogue
The efficacy of the meglitinides is similar to
that of the sulfonylureas, leading to a
decrease in the fasting plasma glucose
level of about 60 mg/dL (3.3 mmol/L) and
in HbA1c of 1.7% to 1.9% compared with
placebo
The main disadvantages of the meglitinides
are their frequent dosing requirements and
the risk for hypoglycemia and
hyperinsulinemia, which is the same as
with the sulfonylureas.
No long-term data are available on
nonsulfonylurea secretagogues and their
effects on diabetic complication rates.
 EXENATIDE
Adalah: AA peptida sintetik yg berikatan dg
reseptor GLP-1 di seluruh bagian tubuh dan
memberikan aksi glukoregulatori.
Me sekresi glukosa dependent insulin serta
menekan sekresi glukagon PP yang
menyebabkan produksi glula di liver
Mengurangi intake makanan sehingga me BB
Efektivitas:reduksi HbA1c 0,9%, signifikan
menurunkan gula PP, namun efek menengah
pada FPG
ESO: mual, muntah, diare
Dosis: awal 2 x 5mg titrated to 2x10mg , secara
s.c. 30min-1jam sebelum makan
Dipeptidyl peptidase IV inhibitor

Aksi: memperlama T1/2

GLP-1 endogen,
menghambat