Faculty of pharmacy - Cairo University

Pharmacology Department

Prepared by: Mohamed Hussein Abd EL Hady

Supervised by: Dr. Noha Nagah
 Diabetes
Definition:
Diabetes is a disease in which the body does not produce or properly use insulin.
Insulin is a hormone that is needed to convert sugar, starches and other food
into energy needed for daily life. The cause of diabetes continues to be a
mystery, although both genetics and environmental factors such as obesity and
lack of exercise appear to play roles.

There are 23.6 million children and adults in the United States, or 7.8% of the
population, who have diabetes. While an estimated 17.9 million have been
diagnosed with diabetes, unfortunately, 5.7 million people (or nearly one
quarter) are unaware that they have the disease.

In order to determine whether or not a patient has pre-diabetes or diabetes,

health care providers conduct a Fasting Plasma Glucose Test (FPG) or an Oral
Glucose Tolerance Test (OGTT). Either test can be used to diagnose pre-diabetes
or diabetes. The American Diabetes Association recommends the FPG because it
is easier, faster, and less expensive to perform.

With the FPG test, a fasting blood glucose level between 100 and 125 mg/dl
signals pre-diabetes. A person with a fasting blood glucose level of 126 mg/dl or
higher has diabetes.

In the OGTT test, a person's blood glucose level is measured after a fast and two
hours after drinking a glucose-rich beverage. If the two-hour blood glucose level
is between 140 and 199 mg/dl, the person tested has pre-diabetes. If the two-
hour blood glucose level is at 200 mg/dl or higher, the person tested has
diabetes.

Types of Diabetes:
 Item Type І DM Type II DM
Onset or age Called Juvenile onset diabetes Called Matuitary onset
happened at it mellitus or insulin depended diabetes mellitus or non
the disease diabetes mellitus (IDDM) insulin depended diabetes
mellitus (NIDDM)
In young (infants) people <45
years. In adults >45 years.

Causes of Autoimmune disease by Some of β-cells are

disease: formation of Ab against β-
cells which lead to complete
destruction of these cells with
complete absence of insulin
lead to increase in glucose in
blood with increase in
lipogensis and ketoacidosis
lead to diabetic ketoacidosis
(DKA)
destructed but there is
>30% are still work and
release small amount of
insulin so also lead to
elevation in glucose level
in blood

Treatment By insulin By adjust diet , excersie

,oral hypoglycemic

3- Gestational diabetes:
 Combination of inadequate insulin secretion and responsiveness,
resembling type 2 diabetes.
 Develop during pregnancy and may improve or disappear after
delivery and it may be transient.
 May damage the health of the fetus or mother, and about 20%–50%
of women with gestational diabetes develop type 2 diabetes later in life.

Signs and symptoms:

Polyphagia, Polydipsia, Polyuria, Fatigue, Blurred vision, Weight loss, Poor wound
healing, Dry mouth, Dry or itchy skin, Impotence (in males), recurrent
infections.

Complications of uncontrolled DM:

Microvascular: cataract, retinopathy, nephropathy, neuropathy
Macrovascular: CHD, Atherosclerosis

New Drugs in treatment of Diabetes

1- Oral Insulin
Oral insulin is a reality: it is simply a matter of when.
Obviously, the priority in delivering insulin to a patient is to make sure it reaches
the bloodstream intact.

Many alternative delivery systems, although they work to some extent, leave the
insulin broken down by digestive juices. Furthermore, the complicated
environment within the stomach means that simple tablets would be
unpredictable and ineffective. The solution will come, and may have already,
when a pharmaceutical research company creates a tablet in which insulin can
be enclosed and yet still pass through the stomach wall.

Three principal target areas are obvious in developing alternative insulin delivery
systems: the nose, the mouth and the lungs.

One product that is already available in Ecuador, India, and on a very limited
basis, Canada, is Oral-lyn, a formulation of Regular insulin that is sprayed into
the mouth using a device similar to an asthma inhaler.

Oramed Pharmaceuticals, is also developing a noninjectable insulin. Presently in

clinical trials to assess safety and effectiveness, this drug is a form of Regular
insulin in oral capsules. It will initially be intended for use in people with Type 2
diabetes. The capsules are specially formulated to avoid breakdown in the
stomach. The insulin is absorbed in the intestine and then travels first to the
liver.

According to the company, routing insulin to liver more closely mimics what
normally happens in a person without diabetes than injecting or infusing insulin
under the skin. This helps to lower the blood glucose level, relieving some of the
burden on the pancreas to produce insulin, and help to preserve pancreatic
function for longer.

A set of researchers funded by the Indian

government is also in the process of developing an
insulin pill, which is scheduled to be studied in
human trials within several months. This pill uses
nanoparticles to deliver insulin to the bloodstream.
Additional methods of insulin delivery are
sublingual insulin; inhalable insulin; and insulin
suppositories.

Oral-Lyn - Oral Insulin for Types 1 and

2 Diabetes

Key Data:
Company / licensee: Generex Biotechnology
Product description: Oral spray formulation of human insulin

Under development by Canadian company Generex Biotechnology, Oral-Lyn is

an oral spray formulation of human insulin indicated for the treatment of type 1
and 2 diabetes.
Generex Oral-lyn is a safe, simple, fast, effective, and pain-free alternative to
subcutaneous insulin and is conveniently delivered to the membranes of the oral
cavity by a simple device with no pulmonary deposition. As a pain-free and
convenient method of insulin delivery, Generex Oral-lyn will allow individual
patients to "fine tune" and then maintain their metabolism resulting in an
improved quality of life.

Oral-Lyn is already approved in Ecuador and Generex is also preparing to file

for approval of Oral-lyn in Columbia, Peru and Bolivia, and will further scale-up
production.

Generex's Oral-Lyn is a liquid formulation of human insulin that is sprayed into

the mouth using its proprietary RapidMist device. In the mouth the insulin is
absorbed via the buccal mucosa. Generex believes that Oral-Lyn will provide an
effective alternative to prandial insulin injections and improve patient
compliance.

Evidence of efficacy in diabetic patients

Approval of Oral-Lyn by the Ecuadorian Ministry of Public Health was based on
data from clinical trials conducted in Ecuador which involved more than 250
patients with type 2 diabetes. These showed that Oral-Lyn had comparable
efficacy to prandial insulin injections in this patient population.

The company is also hoping to extend use of Oral-Lyn in Ecuador to type 1

diabetic patients and has already initiated a six-month study of its safety and
efficacy in adolescent and young adult patients with type1 diabetes.

The real test of the product's viability will come from large-scale trials involving
several thousand patients that will be required by regulatory authorities in North
America and Europe. Plans are underway for phase III trials in Canada and
Europe to be followed by similar large-scale studies in the US.

A- AlveairTM by Coremed Co.

Alveair™ is an inhaled insulin delivery system which has the potential to provide
patients with diabetes a “needle-less” alternative to current insulin injections
using a generic hand-held device that delivers inhaled insulin with the same
units as conventionally injected insulin, making it possible to substitute
injectable insulin.

The device is capable of delivering any amount between 0.2 to 200 units in one
single dose administration. The median mass diameter (MMD) of the vaporized
droplet size is 1.9 um. All steps in the administration of Alveair exactly follow
the current clinical practice of insulin injection, including packaging, storage and
dosages. The only difference is that humans inhale Alveair, with no need to
needles.

Efficacy & Bioavailability

Based on pre-clinical data, Alveair achieves insulin bioavailability of intravenous
injections of analog insulin. Multiple experiments were performed comparing
Alveair to intravenous and subcutaneous injections in two different animal
models, rats and guinea pigs. Alveair demonstrated delayed insulin peak and
better AUC compared to intravenous insulin. Alveair peaked slowly over many
hours, whereas Aspar i.v. peaked around 15 minutes. The data variations were
minimal and its glucodynamic profiles were uniform. Alveair showed superior
efficacy and bioavailability, equaling or surpassing both subcutaneous and
intravenous injections of analog insulin.

Alveair bioavailability is the highest of any insulin in the current reported

literature, with close to 100% bioavailability. The current leading inhaled insulin
technology is approximately one tenth of the efficacy and 15% of the
bioavailability of an injection. Its glucose-lowering action is relatively short-lived.
Alveair bioavailability is close to 100% of the injection and has a longer
duration of action.

Safety
The lungs are sensitive to particles, whether they are inert or biologically
inactive. Any residues, including insulin, can be potentially harmful to the lungs.
Based on its animal studies, Alveair found to be extremely clean, leaving "no
residue". Safety and tolerability of inhaled insulin technologies depend on:

• The physical characteristics of the formulation

• Insulin dosage
• Insulin concentration
• Location of drug deposition
• Recipients

Key advantages of Alveair ™ include:

• It is completely aqueous soluble.
• It is vaporized before inhalation.
• It has been demonstrated, in pre-clinical trials, to have excellent
efficacy in the upper airway when delivered intra-nasally or intra-
tracheally.
• It uses the lowest insulin concentration and dosage.
• It has very low residue.

Thus, Alveair not only have the

potential to replace insulin
injections in many clinical
conditions; it also can lower
insulin’s side-effect profile.

2- Incretins
Mimetics
Incretins are a type of
gastrointestinal hormones that cause
an increase in the amount of insulin
released from the beta cells after
eating, even before blood glucose
levels become elevated. They slow
the rate of absorption of nutrients
into the blood stream by reducing
gastric emptying and may directly reduce food intake. They also inhibit glucagon release
from the alpha cells. The two main molecules that fulfill criteria for an incretin are
glucagon-like peptide-1 (GLP-1) and Gastric inhibitory peptide (aka glucose-dependent
insulinotropic peptide or GIP). Both GLP-1 and GIP are rapidly inactivated by the
enzyme dipeptidyl peptidase 4 (DPP-IV).

A- Exenatide: (Byetta®)

Exenatide is the first type incretin mimetics approved by FDA for the treatment
of diabetes mellitus type 2 (not approved for use in diabetes mellitus type 1).

Exenatide is administered as a subcutaneous injection of the abdomen, thigh,

or arm, 30 to 60 minutes before the first and last meal of the day.

The main side effects of exenatide are gastrointestinal, including sour stomach,
belching, diarrhea, heartburn, indigestion, nausea, and vomiting. Other side
effects include dizziness, headache, and feeling jittery.

Drug interactions include delayed or reduced concentrations of Lovastatin,

Acetaminophen, and Digoxin, although this has not been proven to alter the
effectiveness of these other medications.

In response to post-marketing reports of acute pancreatitis in patients using

exenatide, FDA added a warning to the labeling of Byetta in 2007.

Chemistry and Pharmacology

Exenatide is manufactured by Amylin Pharmaceuticals and Eli Lilly & Co.. It is a
synthetic version of exendin-4, a hormone found in the saliva of the Gila
monster. It displays biological properties similar to human glucagon-like peptide-
1 (GLP-1).

Byetta enhances glucose-dependent insulin secretion, suppresses

inappropriately elevated glucagon secretion, and slows gastric emptying.

Exenatide is a 39-amino-acid peptide an insulin secretagogue with

glucoregulatory effects. Exenatide was approved by the FDA on April 28, 2005
for patients whose diabetes was not well-controlled on other oral medication.
The medication is injected subcutaneously twice per day using a pre-filled pen
device.

GLP-1 and GIP stimulate insulin secretion from the beta cells of the islets of
Langerhans in the pancreas. Only GLP-1 causes insulin secretion in the diabetic
state; however; GLP-1 itself is ineffective as a clinical treatment for diabetes as
it has a very short half-life in vivo. Exenatide bears a 50% amino acid
homology to GLP-1 and it has a longer half-life in vivo. Thus, it was tested for its
ability to stimulate insulin secretion and lower blood glucose in mammals and
was found to be effective in the diabetic state. In studies on rodents it has also
been shown to increase the number of beta cells in the pancreas.
Commercially, exenatide is produced by direct chemical synthesis. Historically,
exenatide was discovered as a protein naturally secreted in the saliva and
concentrated in the tail of the Gila monster.

Exenatide is approved "as adjunctive therapy to improve glycemic control in

patients with type 2 diabetes mellitus who are taking metformin, a biguanide, or
a combination of metformin and a sulfonylurea but have not achieved adequate
glycemic control". It has now been approved for use with thiazolidinediones such
as pioglitazone or rosiglitazone.

Exenatide raises insulin levels quickly (within 10 minutes) with the insulin levels
subsiding substantially over the next hour or two. A dose taken after meals has
a much smaller effect on blood sugar than one taken beforehand. The effects on
blood sugar diminish after 6–8 hours. The medicine is available in two doses:
5 mcg and 10 mcg. Treatment often begins with the 5 mcg dosage, which is
increased if adverse effects are not significant.

The Byetta autoinjector must be stored in a refrigerator between 2°C & 8°C
before first use, and then between 2°C & 25°C. In hot weather they should be
refrigerated. Byetta pens contain sixty doses designed to be used twice a day for
30 days.

Mode of action
Exenatide is believed to facilitate glucose control in at least four ways:
• Exenatide increases insulin secretion in response to eating; so release
higher and more appropriate amount of insulin that helps lower the rise in
blood sugar from eating. Once blood sugar levels decrease closer to
normal values, the pancreas response to produce insulin is reduced (i.e. no
hypoglycemia).
• Exenatide suppresses release of glucagon in response to eating, so
helps stop liver from overproducing sugar when unneeded, so prevents
hyperglycemia.
• Exenatide helps slow down gastric emptying and thus decreases the
rate at which meal-derived glucose appears in the bloodstream.
• Exenatide has a subtle yet prolonged effect to reduce appetite,
promote satiety via hypothalamic receptors (different receptors than for
amylin). Most people using Exenatide slowly lose weight, and generally
the greatest weight loss is achieved by people who are the most
overweight at the beginning of exenatide therapy.
• Exenatide reduces liver fat content. Fat accumulation in the liver or
non-alcoholic fatty liver disease is strongly related with several metabolic
disorders, in particular low HDL cholesterol and high triglycerides, present
in patients with type 2 diabetes.

In an open-label randomized controlled trial of 551 patients, exenatide

treatment for 26 weeks was associated with 2.3 kg weight loss; however,
gastrointestinal symptoms were more common in the exenatide group,
including nausea (57.1%), vomiting (17.4%) and diarrhea (8.5%). For most
patients, the nausea is mild to moderate and goes away entirely after a few days
or weeks.
Advantages: While other treatment options share one or more of the first three
characteristics, some diabetic's specialists view exenatide as a significant
improvement over other available diabetic medications, although most doctors
do not use it as primary therapy at this time. Except for metformin and
acarbose, all other available drugs for improving glucose control have been
associated with weight gain.

Disadvantages: In addition to gastrointestinal adverse reactions, a relative

disadvantage of exenatide is that it is administered by injection. See side
effects section below.

Indications
• Adjunctive therapy in patients with type 2 diabetes who are taking
metformin, a sulfonylurea, thiazolidinediones, or a combination of
metformin and sulfonylurea or thiazolidinediones.
• Use with insulin, meglitinides & α-glucosidase inhibitors has not been
studied.
• Some physicians use exenatide as primary monotherapy, although
this is not currently an FDA approved usage.

Note: Since the major action of this drug is to enhance the release of
endogenous insulin from the pancreas, exenatide is not for use in Type 1
diabetes.

Side effects
• May increase risk of sulfonylurea-induced hypoglycemia. If take both drugs
you may need to take a lower dose of the sulfonylurea to prevent
hypoglycemia.
• Gastrointestinal side effects have raised concern.
• Patients taking exenatide may be at risk for acute pancreatitis
according to FDA. However a causal relation has not been shown yet.
• People with severe kidney disease should not take exenatide.

Future research
Eli Lilly & Co., Amylin Pharmaceuticals and Alkermes are currently developing a
long-acting-release formula of the drug, which would be injected once per week.
The initial trials for the medication shown that long-acting-release formula
approximately twice as effective as the original twice-daily injectable form, with
a similar safety, lower nausea rates and greater weight loss profile. Phase III
study showed that 50% of patients treated with exenatide LAR had an A1C of
6.5% or better, and 75% reached 7.0%. study published in 2008 also showed
that the long-acting formulation resulted in a greater HbA1c decline and more
patients reaching HbA1c targets.

B-Liraglutide

Key Data
Drug (Brand/Generic): Liraglutide.
Company/Licensee: Novo Nordisk.
Therapy Class: GLP-1 analogue.
Product Description: Long-acting human analogue of GLP-1.
Route of administration: Once-daily subcutaneous injection.
Current Indication: Type 2 diabetic patients poorly controlled with diet plus
metformin and/or sulfonylureas.
Development Status: Pre-registration US, Europe, and Japan.

Liraglutide (NN2211), if approved will be marketed under brand-name

"Victoza", is a long-acting GLP-1 analog that is being developed by Novo Nordisk
for the treatment of type 2 diabetes. These mirror the effects of naturally
produced GLP-1.

Pharmacodynamics
Studies to date suggest liraglutide improves control of blood glucose. It
reduces meal-related hyperglycaemia (for 12 hours after administration) by
increasing insulin secretion, delaying gastric emptying, and suppressing prandial
glucagon secretion.

Liraglutide may have advantages over current therapies:

• It acts in a glucose-dependent manner.
• It has the potential for inhibiting apoptosis and stimulating
regeneration of beta cells.
• It decreases appetite and maintains body weight.
• It lowers blood triglyceride levels.
• It has only mild and transient side effects, mainly gastrointestinal.

Pharmacokinetics
Liraglutide is a once-daily GLP-1 derivative for the treatment of type 2
diabetes. GLP-1 in its natural form is short-lived in the body (half-life after
subcutaneous injection is approximately one hour) so it is not very useful as a
therapeutic agent. However, liraglutide has a half-life after subcutaneous
injection of 11–15 hours, making it suitable for once-daily dosing.

The prolonged action of liraglutide is achieved by attaching a fatty acid

molecule at one position of the GLP-1 molecule, enabling it to bind to albumin
within the subcutaneous tissue and bloodstream. The active GLP-1 is then
released from albumin at a slow, consistent rate. Binding with albumin also
results in slower degradation and reduced elimination by the kidneys.

"LEAD" clinical trials demonstrate efficacy

Clinical effectiveness of liraglutide is being evaluated in a series of clinical trials
as part of the Liraglutide Effect and Action in Diabetes, or LEAD
programme, which consists of a series of randomised, double-blind controlled
studies. These trials will assess the clinical effectiveness of liraglutide in some
3,800 patients with type 2 diabetes whose blood glucose is inadequately
controlled with standard oral therapies.

The release of data from three of these major phase III studies suggests that
the addition of liraglutide to ongoing oral antidiabetic drugs can significantly
improve glycaemic control in previously uncontrolled type 2 diabetics.
In LEAD 1, 1026 patients receiving maximal dose glimepiride were subsequently
randomised to treatment with liraglutide, rosiglitazone or placebo, liraglutide
achieved significantly better glucose control (HbA1c <7%) than rosiglitazone.

In LEAD 2, 1026 patients receiving maximal dose metformin were subsequently

randomised to treatment with liraglutide, glimepiride or placebo, the
improvement in HbA1c was similar in the liraglutide and glimepiride treatment
arms.

In LEAD 5, 581-patient study, addition of liraglutide to metformin and

glimepiride saw over 50% of patients achieving good glycaemic control (HbA1c
<7%) with over 35% an HbA1c of <6.5%. The reduction in HbA1c achieved with
liraglutide was >0.2% better than that achieved in the active comparator arm
(insulin glargine).

Most recently, data from the LEAD 6 trial showed that liraglutide was
significantly more effective at improving glycaemic control in patients with type 2
diabetes than exenatide. In this 376-patient study, patients were assigned 26-
weeks treatment with either exenatide or liraglutide. At end of this period,
patients on exenatide were switched to liraglutide. Statistically significant
improvements were seen with respect to reductions in HbA1c, fasting plasma
glucose and blood pressure.

These findings suggest that treatment with liraglutide is at least as good if not
better than standard antidiabetic therapies.

C-Inhibitors of the regulatory protease dipeptidyl

peptidase-IV (DPP-IV)
DPP-4 inhibitors include Januvia, approved in the U.S. and Europe, and Galvus,
approved in Europe but not in the U.S.
DPP-IV inhibitors are currently under development in preclinical and clinical
studies as potential drugs for the treatment of type 2 diabetes based on the
observation that DPP-IV rapidly inactivates GLP-1. DPP-IV inhibitors stabilise
endogenous GLP-1 at physiological concentrations, and induce insulin secretion
in a glucose-dependent manner so no hypoglycaemic effects. Furthermore, they
are orally bioavailable.

DPP-IV inhibitors also stabilise other incretins, including gastric inhibitory peptide
and pituitary adenylate cyclase-activating peptide. They also reduce the
antagonistic and desensitising effects of the fragments formed by truncation of
the incretins.

In clinical studies, when used for the treatment of diabetes over a 1-year period,
DPP-IV inhibitors show improved efficacy over time. This finding can be
explained by a GLP-1-induced increase in the number of beta cells.

Potential risks include the prolongation of the action of other peptide hormones,
neuropeptides and chemokines cleaved by the protease, and their interaction
with DPP-IV-related proteases.
 Januvia

Generic Name: sitagliptin

Brand Names: Januvia

Januvia is a once-daily pill that, along with diet and exercise, helps lower blood
sugar levels in adults with type 2 diabetes.

Januvia works only when blood sugar levels are high

Because januvia stops working before blood sugar gets too low (i.e. no
hypoglycemia). When januvia is used with a sulfonylurea hypoglycemia can
occur. To avoid this risk, doctor may prescribe lower doses of the sulfonylurea.

Most people who took januvia did not gain weight.

Januvia works differently

• Increase the insulin made in your pancreas
• Decrease the sugar made in your liver

Indications and usage

Januvia is indicated as an adjunct to diet and exercise to improve glycemic
control in patients with type 2 diabetes mellitus. Januvia is indicated for:
• Monotherapy
• Combination therapy with metformin or peroxisome proliferatoractivated
receptor gamma (PPARγ) agonist (e.g., thiazolidinediones).
• Januvia should not be used in patients with type 1 diabetes mellitus
(type1 diabetes) or for the treatment of diabetic ketoacidosis.

Possible side effects

The most common side effects of januvia include:
• Upper respiratory infection, Stuffy or runny nose and sore throat,
Headache.

Januvia may occasionally cause stomach discomfort and diarrhea.

The following additional side effects have been reported in general use with
januvia:
• Allergic reactions including rash, hives, and swelling of the face, lips,
tongue, and throat that may cause difficulty in breathing or swallowing. If
you have an allergic reaction, stop taking januvia and call doctor. Doctor
may prescribe a medication to treat allergic reaction and a different
medication for diabetes.

Januvia has not been studied with insulin and should not be used to treat
patients with type1 diabetes or diabetic ketoacidosis. Doctor may perform blood
tests from time to time to measure how well kidneys are working. If patient has
kidney problems, doctor may prescribe lower doses of januvia.

FDA pregnancy category B. Januvia is not expected to be harmful to an unborn

baby. Tell doctor if you are pregnant or plan to become pregnant during
treatment. It is not known whether sitagliptin passes into breast milk or if it
could harm a nursing baby.

I- Eucreas (metformin, vildagliptin)

Main Use: Type 2 diabetes
Active Ingredient: Vildagliptin, metformin hydrochloride.
Manufacturer: Novartis

How does it work?

Eucreas tablets contain two active ingredients, metformin and vildagliptin.
These are both medicines used to help control blood sugar levels in people with
type 2 diabetes.

Metformin (biguanide) works in a number of ways to decrease the amount of

sugar in the blood. Firstly, it reduces the amount of sugar produced by cells in
the liver. Secondly it increases the sensitivity of muscle cells to insulin. This
enables these cells to remove sugar from the blood more effectively. Finally, it
also delays absorption of sugar from the intestines into the bloodstream after
eating.

This combination of medicines helps control blood sugar levels both directly after
meals and between meals.

Eucreas tablets should be taken with or after food.

What is it used for?

• Type2 diabetes
Eucreas tablets are licensed for use in people with type 2 diabetes whose blood
sugar is not controlled by the maximum tolerated dose of metformin alone or
who are already taking metformin and vildagliptin as separate tablets.

Warning!
• Hypoglycaemia has been commonly reported with this medicine.

• Ability to concentrate or react may be reduced if you have low blood

sugar.

• Avoid drinking alcohol while taking this medicine, as it can increase

the risk of hypoglycaemia and lactic acidosis.

• Metformin can cause a rare but serious condition called lactic

acidosis. It is more likely to occur in people with decreased kidney
function. Drinking excessive amounts of alcohol while taking this medicine,
particularly on an empty stomach or if you have liver problems, can
increase the risk of lactic acidosis.

• Kidney function should be monitored regularly while taking this

medicine.

• Rare cases of inflammation hepatitis have been reported.

 • Doctor will ask you to stop taking this medicine temporarily if you
are going to have a certain type of X-ray involving an injection of iodinated
dye.

• Consult doctor about diabetes treatment if you are due to have

surgery under a general anaesthetic. In these situations blood sugar is
normally controlled by insulin.

Use with caution in

• Elderly people.
• People taking ACE inhibitor medicines.

Not to be used in
• Type 1 diabetes.
• Diabetic ketoacidosis.
• Diabetic pre-coma.
• Decreased kidney function & Kidney failure.
• Decreased liver function.
• Heart failure & recent heart attack.
• Respiratory failure.
• Reduced blood flow to vital internal organs (shock).
• Severe infections or trauma.
• Children and adolescents under 18 years of age because it hasn’t
been studied in this group.

Pregnancy and breastfeeding

• This medicine should not be used during pregnancy because its
safety has not been established. Diabetes is usually controlled using insulin
during pregnancy.

• It is not known if vildagliptin passes into breast milk, however

metformin does. As it could have side effects on a nursing infant, so not
used by breast feeding.

Side effects
Very common (affects more than 1 in 10 people)
• Disturbances of the gut such as diarrhoea, nausea, vomiting or
abdominal pain.
• Loss of appetite.

Common (affects between 1 in 10 and 1 in 100 people)

• Dizziness.
• Headache.
• Tremor.
• Metallic taste.
• Low blood sugar levels (hypoglycaemia).

How can this medicine affect other medicines?

Cimetidine may increase the blood level of metformin, which could increase the
risk of its side effects. Doctor may need to reduce dose of this medicine if you
take cimetidine as well.

Medicines that increase blood sugar levels as a side effect may make this
medicine less effective at controlling blood sugar including: Corticosteroids,
levothyroxine, thiazide diuretics.