DRUGS OF DIABETTES .

Submitted to Ma’am Maira Riaz.

Subject; Pharmacy.
Submitted by:
GROUP NO.9

MEMBERS:
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Shiza Arif 044
Maham Imran 057
Musffarah Tahir 093
Ayesha Abbas 041
Iman Elvi 059

1
Contents
Insulin preparation and treatment:....................................................................................................8
It is important that any change change in insulin treatment be made cautiously by clinician,with strict
attention paid to the dose,when their peak level’s occur and their durations..........................................8
Rapid-onset and ultrashort -acting insulin preparations.........................................................................8
Four preparations fall into this category:...............................................................................................8
regular insulin, insulin lispro (LIS-proe) insulin aspart (AS-part) and insulin glulisine [gloo-
LYSE- een]. Regular insulin is a short-acting,soluble, crystalline zinc insulin. Regular insulin should
be injected subcutaneously 30 minutes before a meal, whereas rapid-acting insulins are administered
in the 15 minutes proceeding a meal or within 15 to 20 minutes after starting a meal...........................8
Intermediate-acting insulin:...............................................................................................................8
Neutral protamine Hagedorn (NPH) insulin is an intermediate-acting insulin formed by the addition
of zinc and protamine to regular insu- lin. (Note :Another name for this preparation is insulin
isophane.] The combination with protamine forms a complex that is less soluble, resulting in delayed
absorption and a longer duration of action.............................................................................................8
Long-acting insulin preparations:.......................................................................................................8
The isoelectric point of insulin glargine [GLAR-geen] is lower than that of human insulin, leading to
formation of a precipitate at the injection site that releases insulin over an extended period. As with
NPH insulin, insulin glargine and insulin detemir are used for basal control and should only be
adminis- tered........................................................................................................................................8
Insulin combinations:...........................................................................................................................8
Various premixed combinations of human insulins, such as 70% NPH insulin plus 30% regular
insulin or 50% of each of these are also available................................................................................8
Standard treatment versus intensive treatment:.....................................................................................8
Standard insulin therapy involves twice-daily injections. In contrast, intensive treatment utilizes three
or more injections daily with fre- quent monitoring of blood glucose levels. The ADA recommends a
target mean blood glucose level of 154 mg/dL or less..........................................................................8
SYNTHETIC AMYLIN ANALOG:...................................................................................................8
Amylin is a hormone that is cosecreted with insulin from β cells following food intake. It delays
gastric emptying, decreases postprandial glucagon secretion, and improves satiety........................9
Pramlintide may not be mixed in the same syringe with insulin, and it should be avoided in patients
with diabetic gastroparesis (delayed stomach emptying),......................................................................9
INCRETIN MIMETICS:.....................................................................................................................9
Oral glucose results in a higher secretion of insulin than occurs when an equal load of glucose is given
IV. This effect is referred to as the “incretin effect” and is markedly reduced in type 2 diabetes...........9
Mechanism of action:...........................................................................................................................9
The incretin mimetics are analogs of GLP-1 that exert their activity by acting as GLP-1 receptor
agonists. These agents improve glucose- dependent insulin secretion, slow gastric emptying time,
reduce food intake by enhancing satiety (a feeling of fullness).............................................................9
Pharmacokinetics and fate:................................................................................................................9
Being polypeptides, exenatide and liraglutide must be administered subcutaneously. Liraglutide is
highly protein bound and has a long half-life, allowing for once-daily dosing without regard to meals.
Exenatide is eliminated mainly via glomerular filtration and has a much shorter half-life.................9
Adverse effects:....................................................................................................................................9

2
The main adverse effects of the incretin mimetics consist of nausea, vomiting, diarrhea, and
constipation. Exenatide and liraglutide have been associated with pancreatitis....................................9
Oral agents:........................................................................................................................................10
Oral agents are useful in the treatment of patients who have type two diabetes that is not controlled
with diet...............................................................................................................................................10
Sulfonylureas......................................................................................................................................10
✓Sulfonylureas work mainly by stimulating the cells in the pancreas to make more insulin..............10
✓Sulfonylureas in current use are the second generation ones............................................................10
✓The second generation sulfonylureas include glyburide, glipizide, and glimepiride.........................10
Mechanism of action:........................................................................................................................10
Sulfonylureas drug (SUR) enters the body and attaches at the potassium channel causing partial
blockage of the channel causing the potassium ions present in the beta-cells to remain inside the cell.
.............................................................................................................................................................10
This results in depolarization resulting in the opening of calcium channels........................................10
As a results calcium enters the cell causing the insulin to get released and balance blood glucose level.
.............................................................................................................................................................10
Pharmacokinetics and fate................................................................................................................10
Given orally these drugs bind to plasma protein and are metabolized by the liver ............................10
They are then excreted through urine and feces...................................................................................11
Duration of action................................................................................................................................11
12-25 hours..........................................................................................................................................11
Adverse effects:..................................................................................................................................11
Weight gain..........................................................................................................................................11
Hyperinsulinemia................................................................................................................................11
Hypoglycemia.....................................................................................................................................11
Renal impairment is a problem caused by glyburide as it may increase duration of action and
increase risk if hypoglycemia..............................................................................................................11
Glipizide is safer option for patients with renal problems and elderly people......................................11
Glyburide has minimal transfer through placenta and so can be given to pregnant women.................11
Glinides:.............................................................................................................................................11
This class includes repalglinides and nateglinide...............................................................................11
Mechanism of action:........................................................................................................................11
It has the same mechanism of action as sulfonylureas........................................................................11
In contrast to sulfonylureas have rapid onset and short duration of action..........................................11
They are particularly important in early release of insulin that occurs after a meal and are categorized
and postprandial glucose regulators.....................................................................................................11
Sulfonylureas and Glinides should not be used together due to their overlapping mechanisms this
may cause serious risk of hypoglycemia..............................................................................................11
Pharmacokinetics and fate:..............................................................................................................11

3
They should be taken prior to meal and are well absorbed.Both Glinides are metabolized to inactive
products by liver and excreted through bile.........................................................................................11
Adverse effects:..................................................................................................................................11
Although Glinides can cause weight gain and hypoglycemia but not as much as sulfonylureas..........11
By inhibiting hepatitic metabolism the lipid lowering drug gemfibrozil may significantly increase the
effects of repalglinides and concurrent use is contradicted.................................................................12
These drugs should be used with caution in patients with hepatic impairment ...................................12
Glinides are contraindicated in patients with DKA, T1D, or known hypersensitivity to either
nateglinide or repalglinides. Unlike the sulfonylureas, glinides do not carry a special warning about
an associated increased risk of cardiovascular mortality......................................................................12
Members:...........................................................................................................................................12
Pharmacokinetics :............................................................................................................................13
Adverse effects:..................................................................................................................................13
 Drug interaction...........................................................................................................................14
a-Glucosidase inhibitor:....................................................................................................................14
Members..............................................................................................................................................14
Mechanism of action..........................................................................................................................14
Advere effects:...................................................................................................................................15
Depeptidyl Pepetidase-4 inhibitor:...................................................................................................16
Mechanism of action:........................................................................................................................16
Drug combination ;............................................................................................................................17
Adverse effects:..................................................................................................................................18
Sodium glucose contraspoter-2 inhibitor :.......................................................................................18
Mechanism of action:........................................................................................................................18
Pharmacokinetics :............................................................................................................................19
Adverse effects :.................................................................................................................................19
Oral agents:........................................................................................................................................19

_________________________________________

4
Diabetes and Insulin Analogs:
Diabetes:
Diabetes is a chronic, metabolic disease characterised by elevated
levels of blood glucose (or blood sugar), which leads over time to serious
damage to the heart, blood vessels, eyes, kidneys and nerves . A relative or
absolute lack of insulin, as seen in diabetes mellitus, can cause serious
hyperglycemia.
Diabetes mellitus:
Diabetes is not a single disease. Rather, it is a heterogeneous group of
syndromes characterized by elevated blood glucose attributed to a
relative or absolute deficiency of insulin. The American Diabetes
Association (ADA) recognizes four clinical classifications of diabetes.
Type 1 diabetes (formerly insulin-dependent diabetes mellitus)
Type 2 diabetes (formerly non-insulin-dependent diabetes mellitus)
Gestational diabetes
1.Type 1 diabetes:
Type 1 diabetes most commonly afflicts children, adolescents, or
young adults, but some latent forms occur later in life. The disease is
characterized by an absolute deficiency of insulin due to destruction of
ß cells. Without functional ß cells, the pancreas fails to respond to
glucose, and a person with type 1 diabetes shows classic symptoms of
insulin deficiency loss). (polydipsia, polyphagia, polyuria, and weight
Type 1 diabetics require exogenous insulin to avoid severe
hyperglycemia and the life-threatening catabolic state of ketoacidosis.
Cause of type 1 diabetes:
In a normal post absorptive period, constant ß-cell secretion maintains
low basal levels of circulating insulin. A burst of insulin secretion
occurs within 2 minutes after ingesting a meal, in response to transient
increases in circulating glucose and amino acids. This lasts for up to
15 minutes, followed by the postprandial secretion of insulin.
However, without functional ß cells, those with type 1 diabetes can
neither maintain basal secretion of insulin nor respond to variations in
circulating glucose.

Treatment:

5
A person with type 1 diabetes must rely on exogenous insulin to
control hyperglycemia, avoid ketoacidosis, and maintain acceptable
levels of glycosylated hemoglobin (HbA,). The goal of insulin therapy
in type 1 diabetes is to maintain blood glucose as close to normal as
possible and to avoid wide swings in glucose. The use of home blood
glucose monitors facilitates frequent self-monitoring and treatment
with insulin.
2.Type 2 diabetes:
Type 2 diabetes is influenced by genetic factors, aging, obesity, and
peripheral insulin resistance, rather than autoimmune processes. The
metabolic alterations are generally milder than those observed with
type 1 (for example, patients with type 2 diabetes typically are not
ketotic), but the long-term clinical consequences are similar.
Cause of type 2diabetes:
Type 2 diabetes is characterized by a lack of sensitivity of target
organs to insulin. In type 2 diabetes, the pancreas retains some ß-cell
function, but insulin secretion is insufficient to maintain glucose
homeostasis in the face of increasing peripheral insulin resistance. The
ß-cell mass may gradually decline over time in type 2 diabetes. In
contrast to patients with type 1, those with type 2 diabetes are often
obese.
Treatment:
The goal in treating type 2 diabetes is to maintain blood glucose
within normal limits and to prevent the development of long-term
complications. Weight reduction, exercise, and dietary modification
decrease insulin resistance and correct hyperglycemia in some patients
with type
2 diabetes. As the disease progresses, ß-cell function declines and
insulin therapy is often needed to achieve satisfactory glucose levels.
3. Gestational diabetes:
Gestational diabetes is defined as carbohydrate intolerance with onset
or first recognition during pregnancy. Uncontrolled gestational
diabetes can lead to fetal macrosomia (abnormally large body) and
shoulder dystocia (difficult delivery), as well as neonatal
hypoglycemia.
Cause of gestational diabetes:
Pregnant women who can't make enough insulin during late pregnancy
develop gestational diabetes. Being overweight or having obesity is linked to

6
gestational diabetes. Women who are overweight or have obesity may already
have insulin resistance when they become pregnant . Diet, exercise, and
insulin administration are effective in this condition. Glyburide and
metforminmay be reasonable alternatives to insulin therapy for
gestational diabetes.
https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-
diabetes/gestational/symptoms-causes#:~:text=Pregnant%20women%20who
%20can't,resistance%20when%20they%20become%20pregnant.
Treatment:
Treatment for gestational diabetes aims to keep blood glucose levels
equal to those of pregnant women who don't have gestational
diabetes. The treatment always includes special meal plans and
scheduled physical activity, and it may also include daily blood
glucose testing and insulin injections .
https://diabetes.org/living-with-diabetes/life-stages/gestational-diabetes/how-to-treat-
gestational-diabetes#:~:text=Treatment%20for%20gestational%20diabetes%20aims,glucose
%20testing%20and%20insulin%20injections.

Insulin and insulin analogs:

Insulin [IN-su-lin] is a polypeptide hormone consisting of two peptide
chains that are connected by disulfide bonds. It is synthesized as a
precursor (proinsulin) that undergoes proteolytic cleavage to form
insulin and C-peptide, both of which are secreted by the ß cells of the
pancreas.
Insulin secretion is regulated by blood glucose levels, certain amino
acids, other hormones, and autonomic mediators. Secretion is most
7
often triggered by increased blood glucose, which is taken up by the
glucose transporter into the ß cells of the pancreas. There, it is
phosphorylated

by glucokinase, which acts as a glucose sensor. The products of

glucose metabolism enter the mitochondrial respiratory chain and
generate adenosine triphosphate (ATP). The rise in ATP levels causes a
blockade of K+ channels, leading to membrane depolarization and an
influx of Ca+.The increase in intracellular Ca+ causes pulsatile insulin
exocytosis.
Mechanism of action :

Exogenous insulin is administered to replace absent insulin secretion

in type 1 diabetes or to supplement insufficient insulin secretion in
type 2 diabetes.

8
Pharmacokinetics and fate:

Human insulin is produced by recombinant DNA technology using

strains of Escherichia coli or yeast that are genetically altered to
contain the gene for human insulin. Modification of the amino acid
sequence of human insulin produces insulins with different
pharmacokinetic properties. Insulin preparations vary primarily in
their onset and duration of activity. Therefore, it is generally
administered by subcutaneous injection. In a hyperglycemic
emergency, regular insulin is administered intravenously.Continuous
subcutaneous insulin infusion (also called the insulin pump) is another
method of insulin delivery. This method of administration may be
more convenient for some patients, eliminating multiple daily
injections of insulin.The pump is programmed to deliver a basal rate of
insulin. In addition, it allows the patient to deliver a bolus of insulin to
cover mealtime carbohydrate intake and compensate for high blood
glucose.

Adverse reactions to insulin:

Hypoglycemia is the most serious and common adverse reaction to

insulin.Other adverse reactions include weight gain, local injection
site reactions, and lipodystrophy. Lipodystrophy can be minimized by
rotation of injection sites. Diabetics with renal insufficiency may
require a decrease in insulin dose.

9
Insulin preparation and treatment:
It is important that any change change in insulin treatment be made cautiously
by clinician,with strict attention paid to the dose,when their peak level’s occur
and their durations

Rapid-onset and ultrashort -acting insulin preparations

Four preparations fall into this category:

regular insulin, insulin lispro (LIS-proe) insulin aspart (AS-part) and insulin
glulisine [gloo-LYSE- een]. Regular insulin is a short-acting,soluble, crystalline
zinc insulin. Regular insulin should be injected subcutaneously 30 minutes
before a meal, whereas rapid-acting insulins are administered in the 15 minutes
proceeding a meal or within 15 to 20 minutes after starting a meal.

Intermediate-acting insulin:

Neutral protamine Hagedorn (NPH) insulin is an intermediate-acting insulin

formed by the addition of zinc and protamine to regular insu- lin.
(Note :Another name for this preparation is insulin isophane.] The
combination with protamine forms a complex that is less soluble, resulting in
delayed absorption and a longer duration of action.

Long-acting insulin preparations:

The isoelectric point of insulin glargine [GLAR-geen] is lower than that of

human insulin, leading to formation of a precipitate at the injection site that
releases insulin over an extended period. As with NPH insulin, insulin
glargine and insulin detemir are used for basal control and should only be
adminis- tered

Insulin combinations:

Various premixed combinations of human insulins, such as 70% NPH insulin

plus 30% regular insulin or 50% of each of these are also available.

Standard treatment versus intensive treatment:

Standard insulin therapy involves twice-daily injections. In contrast, intensive

treatment utilizes three or more injections daily with fre- quent monitoring of
blood glucose levels. The ADA recommends a target mean blood glucose level
of 154 mg/dL or less

10
SYNTHETIC AMYLIN ANALOG:

Amylin is a hormone that is cosecreted with insulin from β cells following food
intake. It delays gastric emptying, decreases postprandial glucagon secretion,
and improves satiety.

Pramlintide may not be mixed in the same syringe with insulin, and it should be
avoided in patients with diabetic gastroparesis (delayed stomach emptying),

INCRETIN MIMETICS:

Oral glucose results in a higher secretion of insulin than occurs when an equal
load of glucose is given IV. This effect is referred to as the “incretin effect” and
is markedly reduced in type 2 diabetes.

Mechanism of action:

The incretin mimetics are analogs of GLP-1 that exert their activity by acting as
GLP-1 receptor agonists. These agents improve glucose- dependent insulin
secretion, slow gastric emptying time, reduce food intake by enhancing satiety
(a feeling of fullness)

Pharmacokinetics and fate:

Being polypeptides, exenatide and liraglutide must be administered

subcutaneously. Liraglutide is highly protein bound and has a long half-life,
allowing for once-daily dosing without regard to meals. Exenatide is eliminated
mainly via glomerular filtration and has a much shorter half-life.

Adverse effects:

The main adverse effects of the incretin mimetics consist of nausea, vomiting,
diarrhea, and constipation. Exenatide and liraglutide have been associated
with pancreatitis.

11
Oral agents:

Oral agents are useful in the treatment of patients who have type two diabetes
that is not controlled with diet.

Sulfonylureas

✓Sulfonylureas work mainly by stimulating the cells in the pancreas to make

more insulin.

✓Sulfonylureas in current use are the second generation ones.

✓The second generation sulfonylureas include glyburide, glipizide, and

glimepiride.

Mechanism of action:

Sulfonylureas drug (SUR) enters the body and attaches at the potassium
channel causing partial blockage of the channel causing the potassium ions
present in the beta-cells to remain inside the cell.

This results in depolarization resulting in the opening of calcium channels.

As a results calcium enters the cell causing the insulin to get released and
balance blood glucose level.

Pharmacokinetics and fate

Given orally these drugs bind to plasma protein and are metabolized by the liver
.

12
They are then excreted through urine and feces.

Duration of action

12-25 hours

Adverse effects:

Weight gain

Hyperinsulinemia

Hypoglycemia

Renal impairment is a problem caused by glyburide as it may increase

duration of action and increase risk if hypoglycemia.

Glipizide is safer option for patients with renal problems and elderly people.

Glyburide has minimal transfer through placenta and so can be given to

pregnant women.

Glinides:

This class includes repalglinides and nateglinide.

Mechanism of action:

It has the same mechanism of action as sulfonylureas.

In contrast to sulfonylureas have rapid onset and short duration of action.

They are particularly important in early release of insulin that occurs after a
meal and are categorized and postprandial glucose regulators.

Sulfonylureas and Glinides should not be used together due to their

overlapping mechanisms this may cause serious risk of hypoglycemia.

Pharmacokinetics and fate:

They should be taken prior to meal and are well absorbed.Both Glinides are
metabolized to inactive products by liver and excreted through bile.

Adverse effects:

Although Glinides can cause weight gain and hypoglycemia but not as much as
sulfonylureas

13
By inhibiting hepatitic metabolism the lipid lowering drug gemfibrozil may
significantly increase the effects of repalglinides and concurrent use is
contradicted.

These drugs should be used with caution in patients with hepatic impairment .

Glinides are contraindicated in patients with DKA, T1D, or known

hypersensitivity to either nateglinide or repalglinides. Unlike the sulfonylureas,
glinides do not carry a special warning about an associated increased risk of
cardiovascular mortality.

Thiazolidiones :
Thiazolidiones are the glitazones. They are insulin sensitizer. This class
required insulin for their action. They can’t promote its release from b- cells.
Thus, Hyperinsulinemia is not the risk.

Members:
The members of this class are
i) Pioglitazone
ii) Rosiglitazone

Mechanism of action:
The TZDs lower insulin resistance by acting as agonists for the peroxisome
proliferator–activated receptor-γ(PPARγ), .Activation of PPARγ regulates the
transcription of several insulin responsive genes, resulting in increased insulin
sensitivity in adipose tissue, liver, and skeletal muscle
i)Rosiglitazone increases LDL cholesterol
and triglycerides
ii)Pioglitazone decreases triglycerides
iii)Both drugs increase HDL cholesterol.
The TZDs can be used as monotherapy or in combination with other glucose-
lowering agents or insulin.The dose of insulin may have to be lowered when
used in combination with these agents.The ADA recommends pioglitazone as a
second- or third-line agent for type 2 diabetes.Rosiglitazone is less utilized due
to adverse cardiac effects. Explain the mechanism in the fig.1
Fig.1.Thiazolidiones mechanism of action

14
Pharmacokinetics :
TZDs pharmacokinetics is give below
 Well absorbed after oral
administration
 Mostly bound to serum
albumin.
 Both undergo extensive metabolism by different
CYP450 isozymes
 Renal elimination of pioglitazone is negligible
 Majority of active drug and metabolites excreted in the bile and
eliminated in the feces
 Metabolites of rosiglitazone are primarily excreted in the urine
 No dosage adjustment is required in renal impairment.

Adverse effects:

A few adverse effects was reported with these drugs

i) Liver toxicity can occur.Periodic monitoring of liver function is
recommended
ii) Weight gain can occur because TZDs may increase
subcutaneous fat and cause fuid retention.
iii) TZDs have been associated with osteopenia and
increased fracture risk
15
 iv) Pioglitazone may also increase the risk of bladder
cancer
v) There is a potential increased risk of myocardial infarction and death
from cardiovascular causes with rosiglitazone. As a result, use of
rosiglitazone was limited to patients .
Uses:
The uses are
 With metformin, the relief of insulin resistance with the TZDs can cause
ovulation to resume in premenopausal women with polycystic ovary
syndrome.

 Drug interaction
 Drug interaction of TZDs with other drugs.
 i) Addictive with other oral
Hypoglycemic drugs ii) TZDs potentiate
insulin but can cause heart failure
 Pioglitazone induces CYP3A and may cause treatment failure with
simultaneously administered drug which are CYP3A substrate.

a-Glucosidase inhibitor:
It is used in type 2 diabetes mellitus in patients who are inadequately
controlled on diet alone or diet and other oral hypoglycemic agents. It
is competitive inhibitor of intestinal a-glucosidase hydrases and delay
absorption of ingested glucose.

Members
The two members of a-glucosidase inhibitors are
Miglitol
Acarbose

Mechanism of action
Located in the intestinal brush border, α-glucosidase enzymes break
down carbohydrates into glucose and other simple sugars that can be
absorbed
i) Acarbose and miglitol reversibly inhibit α-glucosidase
enzymes.
ii) When taken at the start of a meal, these drugs delay the
digestion of carbohydrates, resulting in lower postprandial
glucose levels. Since they do not
stimulate insulin release or increase insulin sensitivity,

16
 iii) These agents do not cause hypoglycemia when used as
monotherapy.
iv) However, when used with insulin secretagogues or insulin,
hypoglycemia may develop.

Pharmacokinetics

i) It is poorly absorbed.
ii) It is metabolized primarily by intestinal bacteria, and some of
the metabolites are absorbed
iii) It is excreted into the urine
iv) Miglitol is very well absorbed but has no systemic effects.It is
excreted unchanged by the kidney.

Advere effects:
The major side effect are
i) Flatulence
ii) diarrhoea
iii) Abdominal
cramping

17
Adverse effects limit the use of these agents in clinical
practice.Patients with infammatory bowel dis-ease, colonic
ulceration, or intestinal obstruction should not use these drugs.

Depeptidyl Pepetidase-4
inhibitor:

i) Alogliptin
ii) Linagliptin
iii) Saxagliptin
iv) Sitagliptin are orally active dipep-
tidyl peptidase-4 (DPP-4) inhibitors
Use:
It is used for the treatment of type 2 diabetes.

Mechanism of action:
These drugs inhibit the DPP-4 enzyme which is responsible for the
inactivation of incretin hormones such as GLP1. Prolonging the
activity of incretin hormones increases insulin release in response to
meals and reduces inappropriate secretion of glucagon.

Drug combination ;
DPP-4 inhibitors may be used as mono-therapy or in combination with
sulfonylureas, metformin, TZDs, or insulin.
▪︎Unlike incretin mimetics, these drugs do not cause satiety, or fullness,
and are weight neutral.

Pharmacokinetic

18
 The DPP-4
inhibitor are
i) Well absorbed after oral administration. Food does not affect
the extent of absorption.
ii) Alogliptin and sitagliptin are mostly excreted unchanged in
the urine
iii) Saxagliptin is metabolized via CYP450 3A4/5 to an active
metabolite
iv) The primary route of elimination for saxagliptin and the
metabolite is renal route.
v) Linagliptin is primarily eliminated via the enterohepatic system.
All DPP-4 inhibitors except linagliptin require dosage adjustments in
renal dysfunction.

Adverse effects:
DPP-4 inhibitors are well tolerated
with the most common adverse
effects being
i) Nasopharyngitis and
headache
ii) Pancreatitis has occurred with use of all DPP-4
inhibitors.
iii) Strong inhibitors of CYP450 3A4/5, such as ritonavir, atazanavir,
itraconazole, and clarithromycin, may increase levels of
saxagliptin. Therefore, reduced doses of saxa-gliptin should be
used.

Sodium glucose contraspoter-2

inhibitor :
The members of this class are
i) Canaglifozin
ii) Dapaglifozin
are the agents in this category of drugs for type 2 diabetes.

Mechanism of action:
The SGLT2 inhibitor is responsible for reabsorbing filtered glucose in the
tubular lumen of the kidney. By inhibiting SGLT2, these agents decrease
reabsorption of glucose, increase urinary glucose excretion, and lower blood
glucose. Inhibition of SGLT2 also decreases reabsorption of sodium and causes

19
osmotic diuresis. Therefore, SGLT2 inhibitors may reduce systolic blood
pressure. However, they are not indicated for the treatment of hypertension.

Pharmacokinetics :
These agents are
i) Given once daily in the morning.
ii) Canaglifozin should be taken before the frst meal of the day. iii)
Both drugs are mainly metabolized by glucuronidation to
inactive metabolites.
iv) The primary route of excretion for canaglifozin is via the feces, about
one-third of a dose is renally eliminated. These agents should be
avoided in patients with renal dysfunction.

Adverse effects :
The most common adverse effects with SGLT2 inhibitors are
i) Female genital mycotic infections (for example, vulvovaginal
candidiasis)
ii) Urinary tract infections, and urinary frequency.Hypotension
has also occurred, particularly in the elderly or patients on
diuretics.Thus, volume status should be evaluated prior to
starting these agents.

Oral agents:
Both the dopamine agonist bromocriptine and the bile acid sequestrant
colesevelam produce modest reductions in HbA1c.The mechanism of action of
glucose lowering is unknown for both of these drugs

20
Although bromocriptine and colesevelam are indicated for the treat-ment of
type 2 diabetes, their modest efficacy, adverse effects, and pill burden limit their
use in clinical practice.

REFERENCES:

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https://images.app.goo.gl/GPwAo4YpGzcuMaT16
https://images.app.goo.gl/ZY9iynGpPh3qsLrt7

________________________________

21