Diabetes

Diabetes
Pabitra Thapa
Sr. Product Development Officer
Asian Pharmaceuticals Pvt. Ltd.
2017/05/23
Hotel Pagoda
Kathmandu
2017/05/23 1Pabitra Thapa

Diabetes, known medically as diabetes
mellitus, is a metabolism disorder.
food we consume is broken down into
glucose.
 Glucose is a type of sugar in the blood - it
is the main source of food for our bodies
(our cells).

When food is digested it eventually enters
our bloodstream in the form of glucose.
Cells utilize glucose for growth and energy.
 However, without the help of insulin, the
glucose cannot enter into cells.

Insulin,
a hormone, is produced by Beta cells in
the Islets of Langerhans, which are in the
pancrease.
After eating, the pancreas automatically
releases an adequate amount of insulin to
transport the blood glucose into the cells,
which results in lower blood sugar levels.

How insulin works
 Insulin is a hormone that comes from a gland situated
behind and below the stomach (pancreas).
 The pancreas secretes insulin into the bloodstream.
 The insulin circulates, enabling sugar to enter into
cells.
 Insulin lowers the amount of sugar into bloodstream.
 As our blood sugar level drops, so does the
secretion of insulin from pancreas.2017/05/23 8Pabitra Thapa

Insulin
 Under Basal Condition 1 U insulin is secreted per
hour by Pancrease
100 units of insulin are equal to 1 mL.
1 Units = 0.01ml
 Much larger quantity is secreted by human
pancrease by after every meal.
 . in prancrease.pptx

Secretion of insulin from beta cells is
regulated by
1. Chemical
2. Hormonal &
3. Neural mechanism
2017/05/23 Pabitra Thapa 10

Chemical mechanism
In pancrease Beta cells have glucose
sensing mechanism so on entry of glucose
Insulin is secreted
Similarly other chemicals like amino acid,
fatty acids and ketone bodies trigger
the synthesis of insulin though glucose is
the principal regulator in the synthesis of
insulin

•Incretin
Hormones
1. glucose-dependent insulinotropic polypeptide (gastric inhibitory
polypeptide )(GIP) and
2. glucagon-like peptide-1 (GLP-1)
These incretin hormones stimulate glucose-dependent insulin secretion by
pancreatic β-cells and stimulate pancreatic β-cell proliferation.

• glucagon-like peptide-1 (GLP-1)
and
• gastric inhibitory polypeptide
(GIP)
• are secreted from the intestinal L-
and K-cells, respectively, after a
meal.

Hormonal
Somatostatin-Inhibit

Neural
Alpha 2 activation: decrease insulin secretion
Beta 2: increase
 Ach or vagal stimulation cause insulin
secretion

• Insulin serves as a “key” to
open cells, to allow the
glucose to enter -- and allow
to use the glucose for energy.

 In diabetes, the glucose in the bloodstream does not
enter the cells (at all or not enough),
 so glucose builds up until levels are too high,
resulting in a condition called hyperglycemia.
 This happens for one of two main reasons:
1. The body is producing no insulin - as in the
case in Diabetes Type 1
2. The cells do not respond correctly to the insulin
- as occurs in Diabetes Type 22017/05/23 18Pabitra Thapa

Consequently, excessive amounts of
glucose accumulate in the blood.
This blood glucose overload is eventually
passed out of the body in urine.
 Even though the blood has plenty of
sugar, the cells of a person with diabetes
are not getting their crucial energy and
growth requirements.

The role of glucose
 Glucose — a sugar — is a source of energy for the cells
that make up muscles and other tissues.
 Glucose comes from two major sources:
1. Food and
2. liver.
 Sugar is absorbed into the bloodstream, where it enters
cells with the help of insulin.

 Some cells use the glucose as energy. Other cells, such as in
our liver and muscles, store any excess glucose as a substance
called glycogen.
 Our body uses glycogen for fuel between meals.
 When glucose levels are low, such as when we haven't
eaten in a while, the liver breaks down stored glycogen
into glucose to keep glucose level within a normal
range.

How glucagon works
 About four to six hours after we eat, the glucose levels in
our blood decrease, triggering our pancreas to produce
glucagon.
 This hormone signals your liver and muscle cells to
change the stored glycogen back into glucose. These
cells then release the glucose into our bloodstream so our
other cells can use it for energy.

Term Definition
glucose sugar that travels through your blood to fuel our cells
insulin
a hormone that tells your cells either to take glucose from our blood
for energy or to store it for later use
glycogen
a substance made from glucose that’s stored in our liver and muscle
cells to be used later for energy
glucagon
a hormone that tells cells in our liver and muscles to convert
glycogen into glucose and release it into our blood so our cells can
use it for energy
pancreas
an organ in our abdomen that makes and releases insulin and
glucagon2017/05/23 23Pabitra Thapa

What is type 1 diabetes?
 In Type 1 Diabetes, the person's own body has destroyed the
insulin-producing beta cells in the pancreas.
 Diabetes Type 1 is known as an autoimmune disease.
 Person with Diabetes Type 1 does not produce insulin.
 In the majority of cases this type of diabetes appears before the
patient is 40 years old. That is why this type of diabetes is also known
as Juvenile Diabetes or Childhood Diabetes.
 Diabetes Type 1 onset can appear after the age of 40, but it is
extremely rare. About 15 per cent of all diabetes patients have Type 1.

• The more severe form of diabetes is type
1, or insulin-dependent diabetes.
• It’s sometimes called “juvenile” diabetes,

• People with Type 1 have to take insulin regularly in
order to stay alive.
• Diabetes Type 1 is not preventable, it is in no way the
result of a person's lifestyle.
• Whether a person is fat, thin, fit or unfit, makes no
difference to his or her risk of developing Type 1.

Immune System Attacks
 With type 1 diabetes, the body’s immune system attacks part of its
own pancreas. But the immune system mistakenly sees the insulin-
producing cells in the pancreas as foreign, and destroys them.
This attack is known as "autoimmune" disease.
 Insulin serves as a “key” to open our cells, to allow the glucose to
enter -- and allow you to use the glucose for energy.
 Without insulin, there is no “key.” So, the sugar stays -- and builds
up-- in the blood. The result: the body’s cells starve from the
lack of glucose.
 And, if left untreated, the high level of “blood sugar” can damage
eyes, kidneys, nerves, and the heart, and can also lead to coma
and death.

Insulin Therapy
So, a person with type 1 treats the disease
by taking insulin injections.
This outside source of insulin now serves
as the “key” -- bringing glucose to the
body’s cells

What is type 2 diabetes
Person with Diabetes Type 2 has one of two problems, and sometimes
both:
1. Not enough insulin is being produced.
2. The insulin is not working properly - this is known as insulin
resistance.
 The vast majority of patients who develop Type 2 did so because
they were overweight and unfit, and had been overweight and unfit
for some time.
 This type of diabetes tends to appear later on in life. However, there
have been more and more cases of people in their 20s developing
Type 2, but it is still relatively uncommon.
 Approximately 85% of all diabetes patients have Type 2

 The most common form of diabetes is called type 2, or non-insulin
dependent diabetes.
 This is also called “adult onset” diabetes, since it typically develops after
age 35. However, a growing number of younger people are now developing
type 2 diabetes.
 People with type 2 are able to produce some of their own insulin. Often, it’s
not enough. And sometimes, the insulin will try to serve as the “key” to open
the body’s cells, to allow the glucose to enter. But the key won’t work. The
cells won’t open. This is called insulin resistance.
 If blood sugar levels are still high, oral medications are used to help the
body use its own insulin more efficiently. In some cases, insulin injections
are necessary.

Gestational diabetes
• Gestational diabetes develops in some women
when they are pregnant.
Most of the time, this type of diabetes goes
away after the baby is born.
However, in gestational diabetes, one have a
greater chance of developing type 2 diabetes
later in life. Sometimes diabetes diagnosed
during pregnancy is actually type 2 diabetes

•TEST / Screening

Glycated hemoglobin (A1C) test
 This blood test indicates our average blood sugar level for the
past two to three months.
 It measures the percentage of blood sugar attached to
hemoglobin, the oxygen-carrying protein in red blood cells.
 The higher our blood sugar levels, the more hemoglobin we'll
have with sugar attached.
 An A1C level of 6.5 percent or higher on two separate tests
indicates that we have diabetes.
 An A1C between 5.7 and 6.4 percent indicates
prediabetes. Below 5.7 is considered normal.2017/05/23 35Pabitra Thapa

• Random blood sugar test.
• A blood sample will be taken at a random
time.
• Regardless of when we last ate, a random
blood sugar level of 200 milligrams per
deciliter (mg/dL) — 11.1 millimoles per liter
(mmol/L) — or higher suggests diabetes.

Fasting blood sugar test.
 A blood sample will be taken after an overnight fast.
 A fasting blood sugar level less than 100 mg/dL
(5.6 mmol/L) is normal.
 A fasting blood sugar level from 100 to 125 mg/dL
(5.6 to 6.9 mmol/L) is considered prediabetes.
 If it's 126 mg/dL (7 mmol/L) or higher on two
separate tests,we have diabetes.

Oral glucose tolerance test
 For this test, we have to fast overnight, and the fasting
blood sugar level is measured.
 Then we drink a sugary liquid, and blood sugar levels are
tested periodically for the next two hours. ( 1hr, 2hr)
 A blood sugar level less than 140 mg/dL (7.8 mmol/L) is
normal.
 A reading of more than 200 mg/dL (11.1 mmol/L) after two
hours indicates diabetes. A reading between 140 and 199
mg/dL (7.8 mmol/L and 11.0 mmol/L) indicates
prediabetes.

Condition 2 hour glucose Fasting glucose
mmol/l(mg/dl) mmol/l(mg/dl)
Normal <7.8 (<140) <6.1 (<110)
Impaired fasting glycaemia <7.8 (<140) ≥ 6.1(≥110) & <7.0(<126)
Impaired glucose tolerance ≥7.8 (≥140) <7.0 (<126)
Diabetes mellitus ≥11.1 (≥200) ≥7.0 (≥126)

A1C test
(percent)
Fasting Plasma
Glucose test
(mg/dL)
Oral Glucose
Tolerance test
(mg/dL)
Diabetes 6.5 or above 126 or above 200 or above
Prediabetes 5.7 to 6.4 100 to 125 140 to 199
Normal About 5 99 or below 139 or below

OHD
Oral Hypoglycaemic Drugs
These are the group of drugs that lower
the glucose levels and effective orally. The
chief draw back of Insulin is it must be
given given by injection.

A. Enhance Insulin Secretion:
1. Sulfonylurease (SU)
First generation: Tolbutamide
Second generation : Glibenclamide, Glipizide, Glicazide, Glimepiride
2. Meglitinide/ phenylalanine analogues: Repaglinide, Nateglinide
3. DPP-4 ( Dipeptidyl Peptidase -4 inhibitors: Sitagliptin, Vildagliptin,
Saxagliptin, Alogliptin, Linagliptin
B. Overcome Insulin Resistance:
1. Biguanide: Metformin
2. Thiazolidinediones: Pioglitazone
C. Miscellaneous antidiabetic drugs:
1. Alpha Glucosidase inhibitors: Acarbose, Voglibose, Miglitol
2. Amylin analogue: Pramlintide
3. Dopamine D2 receptors agonist: Bromocriptin
4. Sodium glucose cotransport-2 inhibitor: Dapagliflozin

Sulfonylurea drugs.
 These medications stimulate our pancreas to produce
and release more insulin.
 For them to be effective, pancreas must produce
some insulin on its own. Second-generation
sulfonylureas such as glipizide, glyburide and
glimepiride (Amaryl) are prescribed most often.
 The most common side effect of sulfonylureas is low
blood sugar, especially during the first four months
of therapy.

• Meglitinides.
• These medications, such as repaglinide
have effects similar to sulfonylureas, but
not as likely to develop low blood sugar.
Meglitinides work quickly, and the results
fade rapidly.

Biguanides.
 Metformin is the only drug in this class
 Metformin decreases blood glucose levels by 1.
decreasing hepatic glucose production, 2. decreasing
intestinal absorption of glucose, and 3. improving insulin
sensitivity by increasing peripheral glucose uptake
and utilization
 It works by inhibiting the production and release of
glucose from our liver,.
 One advantage of metformin is that is tends to cause less
weight gain than do other diabetes medications.

Alpha-glucosidase inhibitors.
 These drugs block the action of enzymes in our digestive
tract that break down carbohydrates.
 That means sugar is absorbed into our bloodstream more
slowly, which helps prevent the rapid rise in blood sugar
that usually occurs right after a meal
 Drugs in this class include acarbose and miglitol .
 Although safe and effective, alpha-glucosidase inhibitors
can cause abdominal bloating, gas and diarrhea. If taken
in high doses, they may also cause reversible liver
damage.2017/05/23 49Pabitra Thapa

Thiazolidinediones.
 These drugs make our body tissues more sensitive to
insulin and keep our liver from overproducing glucose.
 Side effects of thiazolidinediones, such as rosiglitazone
and pioglitazone hydrochloride include swelling,
weight gain and fatigue. A far more serious potential side
effect is liver damage.
 The thiazolidinedione troglitzeone (Rezulin) was taken
off the market in March 2000 because it caused liver
failure

DPP-IV
•Dipeptidyl-peptidase-IV
Inhibitors

Dipeptidyl peptidase IV (DPP-4) is a
enzyme that catalyses the inactivation
of Incretin hormones
1. glucose-dependent insulinotropic polypeptide (gastric
inhibitory polypeptide )(GIP) and
2. glucagon-like peptide-1 (GLP-1)
These incretin hormones stimulate glucose-dependent insulin
secretion by pancreatic β-cells and stimulate pancreatic β-cell
proliferation.

The incretin hormones
glucagon-like peptide-1 (GLP-1) and gastric inhibitory
polypeptide (GIP) are secreted from the intestinal L- and
K-cells, respectively, after a meal.
GLP-1
1. stimulates insulin biosynthesis by pancreatic β-cells,
2. inhibits glucagon secretion from pancreatic α-cells &
3. inhibits gastric emptying.
With hyperglycemia, insulin secretion is stimulated via
these incretin hormones.

 The first dipeptidyl-peptidase-IV (DPP-4) inhibitor
for the treatment of type 2 diabetes became available
in 2006.
 Since then, the number of DPP-4 inhibitors has
increased and DPP-4 inhibitors have developed into
an important drug class

• The first DPP4 inhibitor on the market was sitagliptin (Januvia®).
Sitagliptin is available in 3 dose strengths: 100 mg, 50 mg, and 25
mg. The dose is determined by the estimated glomerular filtration
rate (GFR). Doctors should reduce the dose as the patient's GFR
declines.
• The next DPP4 inhibitor is saxagliptin (Onglyza™). The primary
difference between this drug and sitagliptin is that saxagliptin comes
in 2 dose strengths, which are also adjusted based on the estimated
GFR.
• Linagliptin is available in one dose strength; one size fits all in terms
of renal function. linagliptin does not require dose adjustment in
renal impairment, whereas sitagliptin and saxagliptin do

• Linagliptin, as a DPP-4 inhibitor, improve
glycaemic control in patients with Type
2diabetes by enhancing the levels of the
activeforms of GLP-1 and GIP.

• Linagliptin is a novel DPP-4 inhibitor that, in contrast to
the other members of this drug class, is eliminated by a
biliary/hepatic route rather than by renal elimination.
• This property allows the use of linagliptin in type 2
diabetic patients with normal kidney function as well as
in patients with renal insufficiency without dose
adjustments.

 linagliptin is the first DPP-4 inhibitor to be approved
as a once-daily, 5-mg dose and, due to its primarily
non-renal route of excretion, no dosage adjustment is
required for patients with renal or hepatic
impairment.
 The pharmacokinetics and pharmacodynamics of
linagliptin are not affected to a clinically meaningful
degree by race or ethnicity and
 linagliptin has very low potential for drug-drug
interactions.

Insulins and Diabetes Drugs Approved Before 1999
Brand Name Generic Name Approval Date
Humalog 75/25 75% insulin lispro protamine
and 25% insulin lispro
December 1999
Humalog insulin lispro June 1996
Humalog 50/50 50% insulin lispro protamine
and 50% insulin lispro
June 1996
Novolin 70/30 70% NPH and 30% regular June 1991
Novolin R regular (R) June 1991
Novolin N NPH (N) July 1991
Humulin 70/30 70% NPH and 30% regular April 1989
Humulin N NPH (N) October 1982
Humulin R 100U regular (R) Insulin October 1982
Humulin R 500U regular (R) Insulin (5 times
concentration)
October 1982

Insulin and Diabetes Drugs Approved Between 2000-2012
Lucentis ranibizumab August 2012
Janumet XR sitagliptin and metformin HCl extended-
release
February 2012
Jentadueto linagliptin plus metformin hydrochloride February 2012
Bydureon exenatide synthetic January 2012
Juvisync sitagliptin and simvastatin October 2011
Tradjenta linagliptin May 2011
Kombiglyze XR saxagliptin/metformin hydrochloride
extended-release
November 2010
Victoza liraglutide January 2010
Onglyza saxagliptin July 2009
PrandiMet repaglinide/metformin hydrochloride June 2008
Janumet sitagliptin/metformin HCl March 2007
Januvia sitagliptin phosphate October 2006
ACTOplus met pioglitazone hydrochloride and metformin
hydrochloride
August 2005
Levemir insulin detemir June 2005
Byetta exenatide April 2005
Symlin pramlintide March 2005
Apidra insulin glulisine February 2004
Metaglip glipizide/metformin HCl October 2002
Avandamet rosiglitazone maleate and metformin HCl) October 2002
Lantus insulin glargine April 2000
Novolog Insulin aspart November 2001
Novolog 70/30 70% insulin aspart protamine and 30% November 2001

Insulins and Diabetes Drugs Approved Between 2013-2016
Basaglar insulin glargine injection December 16, 2015
Tresiba insulin degludec injection September 25, 2015
Ryzodeg insulin aspart: insulin
degludec
September 25, 2015
Toujeo insulin glargine injection February 25, 2015
Lucentis ranibizumab February 6, 2015
Glyxambi empagliflozin and
linagliptin
January, 2015
Trulicity duglaglutide September 18, 2014
Invokamet canagliflozin and
metformin hydrochloride
August 8, 2014
Jardiance empagliflozin August 1, 2014
Afrezza Inhalation Powder insulin human June 27, 2014
Tanzeum abliglutide May 2014
Farxiga dapaglifozin January 2014
Invokana canagliflozin March 29, 2013
Nesina alogliptin benzoate January 25,2013
Duetact pioglitazone hydrochloride
and glimepiride
January 2013

Safer in Renal Impairment
• Only DPP-4 inhibitors that donot excrete
primarily by kidney but by enterohepatic
system
Only DDP-4 Inhibitors that doesnot need
dose adjustment in renal impairment

• linagliptinLinaglip-5 final.pdf

• HOW LINAGLIP WORKS
• All type 2 diabetes medications work to
help lower our blood sugar, but since no
two people with diabetes are exactly alike
and may respond differently to different
treatments, what works for one person
may not work for another.
• That's why there are many different
classes of diabetes drugs, and each class
works in a different way.2017/05/23 75Pabitra Thapa

• WHAT IS LINAGLIP ?
• LINAGLIP belongs to a class of drugs
called DPP-4 inhibitors. DPP-4 inhibitors
work by increasing hormones that
stimulate our pancreas to produce
more insulin and
• stimulate our liver to produce less
glucose

• Metabolism Following oral administration,
the majority (about 90%) of linagliptin is
excreted unchanged, indicating that
metabolism represents a minor elimination
pathway.
• A small fraction of absorbed linagliptin is
metabolized to a pharmacologically
inactive metabolite,(Hepatic Safety)

• Excretion
• Following administration of an oral
linagliptin dose to healthy subjects,
approximately 85% of the administered
radioactivity was eliminated via the
enterohepatic system (80%) or urine (5%)
within 4 days of dosing.

• Hepatic

• Renal

• Elderly
• No dose adjustment is necessary based
on age.
• However, clinical experience in patients >
80 years of age is limited and caution
should be exercised when treating this
population.

• Body Mass Index (BMI)/Weight
• No dose adjustment is necessary based
on BMI/weight. BMI/weight had no
clinically meaningful effect on the
pharmacokinetics of linagliptin based on a
population pharmacokinetic analysis.

Method of administration
• The tablets can be taken with or without a
meal at any time of the day.
• If a dose is missed, it should be taken as
soon as the patient remembers.
• A double dose should not be taken on the
same day.

• Pediatric Studies characterizing the
pharmacokinetics of linagliptin in pediatric
patients have not yet been performed.

• Pancreatitis

Pregnancy
The use of linagliptin has not been studied in
pregnant women.
 Animal studies do not indicate direct or
indirect harmful effects with respect to
reproductive toxicity .
As a precautionary measure, it is preferable
to avoid the use of linagliptin during
pregnancy.

• Breast-feeding
 Available pharmacokinetic data in animals have shown
excretion of linagliptin/metabolites in milk.
 A risk to the breast-feed child cannot be excluded.
 A decision must be made whether to discontinue breast-
feeding or to discontinue/abstain from linagliptin therapy
taking into account the benefit of breast-feeding for the
child and the benefit of therapy for the woman.

• Oral contraceptives:
co-administration with 5 mg linagliptin did
not alter the steady-state pharmacokinetics
of levonorgestrel or ethinylestradiol.

Brand Name Strength Generic name Company Price
SIPTIN 25 Sitagliptin Quest Rs 15
Siptin 50 25
Siptin 100 35
Gliptin 50 Magnus 24
100 34
Sitaglip 50 Djpl 25
100 Djpl 35

• Enterohepatic circulation refers to
the circulation of biliary acids,
bilirubin, drugs, or other substances from
the liver to the bile, followed by entry into
the small intestine,

• Hepatic metabolism of linagliptin is
minimal and its metabolites, including its
main metabolite CD1790, are
pharmacologically inactive Linagliptin is
not a clinically relevant inhibitor or inducer
of cytochrome P450 isoenzymes (although
it is a weak inhibitor of CYP3A4) It is also
a substrate and a weak inhibitor (that is
not of clinical significance at therapeutic
doses) of P-glycoprotein

• Linagliptin has a very high affinity for its target,
DPP-4, which is present in plasma and tissues, and it
is only released slowly from the enzyme with
unbound, free drug being eliminated quickly
• Thus, linagliptin exhibits high, concentration-
dependent plasma protein binding which results in
very low plasma concentrations of unbound
compound

• It is only this small unbound plasma
fraction that is directly exposed to hepatic
metabolism and excretion.
• In liver disease, a potential impairment in
drug metabolism may occur through
decreased capacity of the metabolizing
enzymes, decreased liver blood flow or
intra/extra-hepatic shunting

• The metabolites of linagliptin have been shown to play only a
minor role in the overall disposition and elimination of the
drug .
• Therefore, because linagliptin is predominantly eliminated
without involvement of the hepatic metabolizing function, we
suggest that the high enzyme binding, in conjunction with a
low rate of hepatic metabolism results in hepato-biliary
excretion of predominantly unchanged linagliptin. The low
concentrations of unbound linagliptin in the circulation suggest
that even patients with severe hepatic impairment may have
sufficient residual liver capacity to meet the limited metabolic
and hepatic excretory needs to eliminate this small fraction of
unbound drug efficiently.

• The most important observation from this
study is that no linagliptin dose reduction
seems to be necessary in subjects with
hepatic impairment, despite the fact that
85% of this DPP-4 inhibitor is excreted
non-renally.
• Br J Clin Pharmacol
• v.74(1); 2012 Jul
• PMC3394131

• Efficacy and safety of linagliptin in type 2
diabetes patients with self-reported
hepatic disorders: A retrospective pooled
analysis of 17 randomized, double-blind,
placebo-controlled clinical trials
• Conclusions
• This large pooled analysis suggests that
linagliptin is effective and well tolerated in
people with T2DM and liver disease.
• DOI: http://dx.doi.org/10.1016/j.jdiacomp.22017/05/23 97Pabitra Thapa

• The 5-mg dose of linagliptin is suitable for
patients with type 2 diabetes mellitus
irrespective of their ethnicity or the
presence of renal or hepatic impairment.
• © 2016 The Authors. Journal of Diabetes
Investigation published by Asian
Association for the Study of Diabetes
(AASD) and John Wiley & Sons Australia,
Ltd

• Unlike any other DPP-4 inhibitor, linagliptin
has a unique structure composed of a
xanthine skeleton, and some compounds
containing this xanthine skeleton have
been found to possess an antioxidant
effect, suggesting that linagliptin may also
possess similar antioxidant properties
• (Kröller-Schön et al., 2012; Ishibashi et al.,
2013).2017/05/23 99Pabitra Thapa

• Thus, linagliptin may potentially have
improving effects on fatty liver, thereby
improving effects on fat. This study also
suggested that serum levels of LDL-C
were significantly improved in patients in
the linagliptin group.

• 72nd annual meeting of the American
Diabetes Association (ADA) held in 2012,
the administration of linagliptin was
reported to result in an improvement in
albuminuria (Groop et al., 2012

• Results of a recent meta-analysis have
shown that the effects of sitagliptin 100 mg
and linagliptin 5 mg were comparable
(Gross et al., 2013).

• CKD
• Chronic kidney disease (CKD),
defined as the presence of increased
urinary albumin excretion and/or
decreased glomerular filtration rate
(GFR), is amajor public health issue.

• Diabetic kidney disease is the leading
cause of end-stage renal disease (ESRD).
• The development of albuminuria is a key
step in the progression of diabetic kidney
disease, and worsening of albuminuria is a
significant predictor of progressive renal
disease

• current recommendations for the treatment
of kidney disease in patients with type 2
diabetes are directed toward a
multifactorial intervention, including
lowering blood pressure, improving
glycemic and lipid control, and reducing
albuminuria

• Inhibitors of the renin
angiotensinaldosterone system (RAAS)
provide renal and CV protection beyond
their ability to lower blood pressure ,and
the beneficial effects of these agents have
been linked to concomitant changes in
albuminuria.
• Thus, reductions in albuminuria in patients
with type 2 diabetes were associated with
a significant reduction in the risk of
progression to ESRD

• These findings suggest that albuminuria
may be an important therapeutic target for
preventing the progression of diabetic
kidney disease and might also offer CV
protection.

However, despite treatment with current
recommended standard therapy for CKD,
including RAAS inhibitors, many patients
with type 2 diabetes have significant
residual albuminuria and continue to
progress toward ESRD .
 Additional treatment options that would
complement the benefit of existing
therapies remain an important unmet
medical need.2017/05/23 109Pabitra Thapa

• In summary, this pooled analysis found
that linagliptin, administered in addition to
stable ACEI or ARB therapy, led to a
significant reduction in albuminuria after
24 weeks of treatment.
• Linagliptin Lowers Albuminuria on Top of
• Recommended Standard Treatment in Patients
• With Type 2 Diabetes and Renal...
• Article in Diabetes care · September 2013

• CONCLUSIONS
• Linagliptin administered in addition to
stable RAAS inhibitors led to a significant
reduction in albuminuria in patients with
type 2 diabetes and renal dysfunction.
This observation was independent of
changes in glucose level or SBP.

Brand Name Strength Generic name Company Price
SIPTIN 25 Sitagliptin Quest Rs 15
Siptin 50 25
Siptin 100 35
Gliptin 50 Magnus 24
100 34
Sitaglip 50 Djpl 25
100 Djpl 35

• Target Customer
Endocrinologist
Cardiologist/ Diabetician
Physicians
Nephrologist

Diabetes

Recommended

Recommended

More Related Content

What's hot

What's hot (19)

Similar to Diabetes

Similar to Diabetes (20)

More from Pabitra Thapa

More from Pabitra Thapa (20)

Recently uploaded

Recently uploaded (20)

Diabetes

Editor's Notes