Liraglutide: Pharmacology, Diagnosis, and Treatment of Diabetes

This report provides a comprehensive overview of Liraglutide, a pharmaceutical drug classified as a long-acting fatty acylated glucagon-like peptide-1 (GLP-1) derivative, primarily used in the treatment of type 2 diabetes and for chronic weight management. The report details Liraglutide's mechanism of action, its role as a GLP-1 receptor agonist, and its approval by the FDA. It explores the drug's effectiveness in regulating glucose levels, reducing the risk of cardiovascular events in diabetic patients, and its application in weight loss programs. The report further examines the common side effects, including pancreatitis and kidney issues, and discusses research findings on the drug's impact on the brain's reward system and its potential for weight reduction. Diagnosis, treatment, and policy aspects, including NICE guidelines are also included. This report provides a thorough analysis of Liraglutide's pharmacology, clinical applications, and implications for patient care.

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Overview
Liraglutide is a pharmaceutical drug with a long-acting fatty acylated glucagon-like peptide-1
(GLP-1), which is classed as a carboxylic acid REFERENCE. Liraglutide is a once-daily GLP-1
derivative for the treatment of type 2 diabetes, its half-life is approximately 11-15 hours making
it appropriate for once-daily dosing [1]. Enzyme is dipeptidyl peptidase 4
Liraglutide is an injectable glucagon-like peptide (GLP-1) receptor agonist [2]. Which was
approved in 2010 by the US FDA as a treatment for type 2 diabetes mellitus (T2DM) as Victoza,
and more recently has been approved at a higher dose as Saxenda, for chronic weight
management [2]? T2DM is one of the most prevalent metabolic disorders which are
characterized by hyperglycemia due to the detection of insulin secretion or also insulin action
[2]. GLP-1 is a natural incretin hormone which is realized from intestinal L-cells in response to
hormonal, neural and nutrient stimuli [3]. As GLP-1 is used for the treatment of T2DM its half-
life is approximately 11-15 hours, which is suitable for once-daily dosing.
Liraglutide is used with an eating routine as well as exercise program to regulate glucose levels
in grown-ups with sort 2 diabetes (situation where the body does not use insulin typically and in

this way is not able to regulate the amount of sugar in the blood) when different drugs did not
regulate levels alright. Liraglutide is likewise used to diminish the danger of a heart assault,
stroke, or passing in grown-ups with sort 2 diabetes mellitus and heart and vein illness.
Liraglutide is not utilized to treat type 1 diabetes (condition in which the body does not deliver
insulin and along these lines can't control the measure of sugar in the blood) or diabetic
ketoacidosis (a genuine condition that may create if high glucose isn't dealt with) [3].
Liraglutide is utilized alongside a lessened calorie diet and exercise intended to help individuals
who are stout or who are overweight and have weight-related therapeutic issues to get in shape
and to keep from recovering that weight. Liraglutide is not utilized to treat type 2 diabetes.
Liraglutide is in a class of drugs called incretin mimetics [13]. It works by helping the pancreas
to discharge the appropriate measure of insulin when glucose levels are high. Insulin enables the
move to sugar from the blood into other body tissues where it is utilized for vitality. Liraglutide
infusion likewise moderates the exhausting of the stomach and may diminish hunger and cause
weight reduction.
Over the period, individuals who have diabetes and high glucose can create genuine or
dangerous intricacies, including coronary illness, stroke, kidney issues, nerve harm, and eye
issues. Utilizing medication(s), rolling out a way of life improvements (e.g., diet, work out,
stopping smoking), and routinely checking your glucose may deal with your diabetes and
enhance your wellbeing. This treatment may likewise diminish your odds of showing some
kindness assault, stroke, or different diabetes-related confusions, for example, kidney
disappointment, nerve harm (numb, chilly legs or feet; diminished sexual capacity in people),
eye issues, including changes or loss of vision, or gum sickness [4]. Your specialist and other

medicinal services suppliers will converse with you about the most ideal approach to deal with
your diabetes.
Liraglutide injection comes as an answer (fluid) in a prefilled dosing pen to infuse
subcutaneously (under the skin) in your stomach, thigh, or upper arm. It is normally infused once
per day with or without sustenance. Utilize liraglutide infusion at around a similar time each day.
Pursue the bearings on your solution mark deliberately, and ask your specialist or drug specialist
to clarify any part you don't get it. Utilize liraglutide infusion precisely as coordinated [12].
The most common side effects of the drug include:
Irritation of your pancreas (pancreatitis): Quit utilizing Victoza® and call your social insurance
supplier immediately on the off chance that you have serious torment in your stomach territory
(midriff) that won't leave, with or without heaving. You may feel the torment from your guts to
your back.
Low glucose (hypoglycemia): The getting low glucose might be higher on the off chance that
you utilize Victoza® with another drug that can cause low glucose, for example, a sulfonylurea
or insulin [5]. Signs and manifestations of low glucose may include: tipsiness or dazedness,
obscured vision, uneasiness, peevishness or mindset changes, perspiring, slurred discourse,
appetite, disarray or sluggishness, unsteadiness, shortcoming, migraine, quick heartbeat, and
feeling jumpy.
Kidney issues (kidney disappointment): In individuals who have kidney issues, looseness of the
bowels, queasiness, and retching may cause lost liquids (drying out), which may make kidney
issues deteriorate.

Genuine unfavourably susceptible responses: Quit utilizing Victoza® and get medicinal
assistance just on the off chance which one has any manifestations of a genuine unfavourably
susceptible response such as swelling of your face, lips, tongue or throat, issues breathing or
gulping, serious rash or tingling, swooning or feeling mixed up, or an exceptionally fast
heartbeat [14].
Gallbladder issues: Gallbladder issues have occurred in a few people who take Victoza. Tell
your medicinal services supplier immediately in the event that you get side effects of gallbladder
issues which may incorporate torment justified or center upper stomach zone, fever, sickness,
and retching, or your skin or the white piece of your eyes turns yellow.
Research
Another investigation finds that diabetes tranquilize liraglutide prompts weight reduction by
following up on a zone of the cerebrum that controls consideration and potentially making
attractive nourishments less fulfilling. The researchers utilized immunohistochemistry to break
down 22 human cerebrum tissue tests for the nearness of GLP-1 receptors, which are protein
atoms that react to the GLP hormone's signal. She said they found- - out of the blue - that GLP-1
is communicated in the human cerebrum. They supposedly observed proof of this articulation on
neurons, or nerve cells, in the cerebral cortex of the forebrain, a region in charge of the higher
idea [6].
The scientists played out the second report in 18 grown-ups with Type 2 diabetes. Participants
received 17 days of either liraglutide, up to 1.8 milligrams, or a fake treatment (sham
medication) in an arbitrary request. At that point following a three-week "washout" of no drug,

similar members received 17 days of the contrary treatment. Members were unconscious which
treatment they got.
On the 17th day of each of the treatments, participants experienced mind filtering with useful
attractive reverberation imaging (fMRI). Amid fMRI, members saw pictures of different
sustenance. In light of profoundly attractive nourishments, for example, cake, cakes, and singed
sustenance, liraglutide diminished reward enactments in the cortex contrasted and pictures of less
alluring nourishments, for example, organic products, vegetables and other low-calorie, low-fat
nourishments [7] [4].
The lowered activation implies that people on liraglutide find profoundly attractive sustenance
less eye-catching and less remunerating than they ordinarily would without liraglutide," Farr
said. "Consequently, this drug may turn out to be better for weight reduction for individuals who
will, in general, eat all the more high-fat sustenance as a reward, for example, when they are
pushed. Our investigation recognizes neural focuses for more successful weight reduction
therapeutics later on [11].
Diagnosis
Liraglutide is a once-everyday injectable subsidiary of human incretin glucagon-like peptide-1
(GLP-1), for treatment of sort 2 diabetes or even obesity.
Type 2 diabetes: Liraglutide enhances regulation of blood glucose. [6] It decreases feast related
hyperglycemia (for a day after organization) by expanding insulin emission (just) when needed
by expanding glucose levels, postponing gastric purging as well as stifling prandial glucagon
secretion. As of 2017, it is vague in the event that they influence a man's danger of death [7].

In like manner to different degrees with other GLP-1 receptor agonists, liraglutide has favorable
circumstances over more conventional treatments for sort 2 diabetes:
 It serves in a glucose-subordinate way, which means it will invigorate insulin discharge
just when the levels of blood glucose are higher than typical, anticipating "overshoot".
Thus, it demonstrates the immaterial danger of hypoglycemia.
 It has the potential for repressing apoptosis and animating recovery of beta cells (found in
creature contemplates).
 It diminishes craving and restrains body weight gain, as appeared in a straight on study
versus glimepiride.
 It brings down blood triglyceride levels.
Obesity: Liraglutide has been endorsed as an injectable extra to a diminished calorie diet and
expanded physical movement for incessant weight administration in grown-up patients. The
predetermined criteria are an underlying weight list (BMI) of 30 kg/m2 or more noteworthy
(large), or 27 kg/m2 or more prominent (overweight), within the sight of something like one
weight-related comorbid condition (e.g. hypertension, type 2 diabetes mellitus, or dyslipidaemia)
[11]. During late 2014, information was accounted for from SCALE™ Obesity and Prediabetes
trial that is randomized, twofold visually impaired, fake treatment controlled, global preliminary
in non-diabetic individuals with heftiness as well as non-diabetic individuals who are overweight
with comorbidities. In this stage 3a preliminary, there were 3,731 members randomized to
treatment using liraglutide 3 mg or fake treatment, both in the mix with eating regimen as well as
exercise. The individuals who finished the 56-week preliminary accomplished a normal weight
reduction of 9.2%, to be contrasted and a 3.5% decrease in the fake treatment group [8].

It is obscure if the weight reduction will be lasting. Hunger concealment might be transitory and
craving may return regardless of whether one keeps on utilizing liraglutide following 56 weeks.
Treatment
Pancreatitis concerns: A meeting at Johns Hopkins in 2013 announced a clearly factually
noteworthy link between hospitalization for intense pancreatitis and earlier treatment with GLP-1
subordinates, (for example, eventide) and DPP-4 inhibitors, (for example, sitagliptin).[17]
accordingly, the United States FDA and the European Medicines Agency directed a survey of
every accessible datum in regards to the conceivable association between incretin mimetics and
pancreatitis or pancreatic malignant growth. In joint 2014 letter to New England Journal of
Medicine, the offices reasoned that "A pooled examination of information from 14,611 patients
with sort 2 diabetes from 25 clinical preliminaries in sitagliptin database gave no convincing
proof of an expanded danger of pancreatitis or pancreatic malignant growth" and "The two
offices are at a consensus that statements concerning a causal link between incretin-based
medications as well as pancreatitis or pancreatic disease, as communicated as of late in the
logical writing and in media, are conflicting with the ebb and flow information [8]. The FDA and
the EMA have not achieved the last end as of now with respect to such a causal relationship. In
spite of the fact that the totality of information that has been looked into gives consolation,
pancreatitis will keep on being viewed as a hazard related with such medications until the point
that more information is accessible; the two organizations keep on researching this security
signal.
Thyroid cancer concerns: At subjections eightfold more prominent than those utilized in
people, liraglutide resulted a factually critical increment in thyroid tumors in rodents. The
clinical importance of such discoveries is not known [9]. In clinical preliminaries, the rate of

thyroid tumors in patients treated using liraglutide was 1.3 per 1000 patient-years (4 individuals)
contrasted with 1.0 for every 1000 patients (1 individual) in examination gatherings. The sole
individual in comparator gathering and four of five people within the liraglutide bunch had
serum markers (hoisted calcitonin) suggestive of prior ailment at baseline. The FDA said serum
calcitonin, a biomarker of medullary thyroid malignancy, was marginally expanded in liraglutide
patients, yet at the same time inside typical reaches, and it required continuous observing for a
long time in a disease library [10].
Policy
Liraglutide is a once every day injectable treatment that demonstrations to assist individuals with
Type 2 diabetes accomplish great glycaemic control by animating the arrival of insulin when
glucose levels get too high and furthermore lessens craving.
NICE has now endorsed Liraglutide 1.2mg once-everyday as a significant treatment alternative
for individuals with Type 2 diabetes as double or triple treatment with an oral treatment.
NICE direction stipulates that medications should just be preceded if blood glucose levels lessen
inside a half year and those experiencing triple treatment figures out how to lose three percent of
their underlying body weight.
NICE suggests considering pharmacological treatment simply after dietary, practice and social
methodologies have been begun and assessed.
The rule prescribes to consider pharmacological treatment for individuals who have not achieved
their objective weight reduction or have achieved a level on dietary, movement and conduct
changes.

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