Semaglutide Mechanism precautions & side effects let us discuss one of the new drug Semaglutide. What is this drug? Semaglutide. The suffix glutide indicates that this drug is acting on diabetes.
And Semaglutide is classified as GLP one receptor agonist. GLP is nothing but glucogone like peptide. So this GLP one can control the blood glucose levels by increasing the insulin secretion from the pancreas. And it also increases the glucagon action which opposes in the elevation of blood glucose levels. In this way, GLP one can control the blood glucose levels, but it is having few of the limitations.
Glucogon like peptide is having a short duration of action and it can be converted into metabolites by one of the enzyme DPP four dipeptidyl peptidase four. So this enzyme can control the action of GLP one. So GLP one shows very short duration of action.
So this is the endogenous mediator which can control the glucose levels, but it has a limitation of short duration of action. Now, Semaglutide is a GLP one receptor agonist, which acts just like GLP one.
So it also increases the insulin secretion as well as Glucon action. But at the same time, this drug is not metabolized by DPP four Nging. That’s why this drug is somewhat long acting and it can control the excessive glucose levels in the diabetic patients. So semaglutide is having two advantages it is not metabolized by DPP four enzyme which increase the bioavailability of this drug. And second important thing is that Simon glutide can bind to albumin.
Semaglutide Mechanism precautions & side effects
When this drug binds to albumin, it cannot be easily metabolized, even it cannot be easily cleared by renal clearance. So this drug can stay within the blood circulation for longer periods. That’s why this drug is one of the long acting GLP one agonist. Hence, semagrotide can be used in the management of type two diabetes mellitus along with diet and exercise. And for this purpose, this drug is available as tablet as well as subcutaneous injection.
Semiclutin not only reduce the glucose levels, but it also reduce the appetite. Thereby it can reduce the body weight. That’s why this drug can be used in the management of obesity. In those patients with body mass index greater than 30 kg per square meter, this semaglotide can be given as subcutaneous injection. But one of the important thing is that the subcutaneous injection which is intended for obesity is not equivalent to the subcutaneous injection indicated for diabetes mellitus.
Since the dosage and strengths are somewhat variable, even root of administration is similar, but they are indicated for different purpose. So this drug is useful in the management of type two diabetes mellitus as well as for management of obesity and particularly among the GLP one agonists. Semaglotide is available as oral formulation to control the diabetes Meritis. Similarly, this drug shows beneficial effect in the management of obesity as it reduces appetite, resulting in the decreased body weight in the patients. But this drug is not indicated in the children.
It is only available for the treatment of obesity in the adults. Apart from these, this drug is having few of the limitations. But semogotide should not be given in the patients with pancreatitis. Since this drug produce a pancreatitis, it is not indicated in the patients with any history of pancreatitis. Similarly, this drug is not useful in the treatment of type one diabetes which is associated with insulin deficiency.
And even semiclutrite is not the first line therapy for the management of diabetes mellitus. It can be combined with other drugs to produce efficient control on blood glucose. And this drug is available as a viral tablet form, which improves the patient comprehension. So today in this , we are going to see how this drug acts. What are the important precautions, dosage forms and what are the doses for different clinical indications.
All these things we will discuss in this . Now let us the chemical nature of this drug. Semiclutride is one of the peptide with different sequence of amino acids, just like the GLP one. But the structure is somewhat modified at two portions. One of the portion is the 26th portion, where this amino acid is going to be replaced with a spacer device combined with C 18 fatty diaceid.
So this improves the binding of semagrotide to the serum albumin, which reduces the clearance and metabolism leading to long duration of action. Similarly, the amino acid at the 8th portion is going to be modified such that this drug is not metabolized by DPP four enzyme. So these two modifications result in the increased stability and increased duration of action. Now, let us see how this drug acts. Semiclutide can produce its action by acting on three organs.
Its main action is attributed to its action on pancreas, where from the beta cells it can increase the insulin secretion, resulting in the decreased glucose levels. Similarly, this drug can act on the brain where it can reduce appetite. So, because of loss of appetite, semaglotide can reduce the body weight. That’s why it can be used in the management of obesity. Similarly, this drug can also produce some delayed gastric emptying, resulting in the decreased absorption of glucose.
By all these actions, semaglutide can be used in the treatment of type two diabetes mellitus as well as in the treatment of obesity. So, on the beta cells, GLP one receptors are expressed, which are G protein coupled receptors coupled with alpha beta gamma subunits. Now, semaglutine can act on this GLP one receptor which results in the activation leading to stimulation of adenyl. Cyclic System by activation of this enzyme, now ATP can be converted into cyclic MP. This cyclic amp plays as an important role within the beta cells.
It can stimulate one group of enzymes protein kinase A. This protein kinasea can control the activity of various ion channels. It can impact the activity of ATP sensor potassium channels through which potassium can go outside and voltage gated calcium channels and voltage gated sodium channels. Now, protein kinasea can inhibit this ATP sense to potassium channels, so that potassium cannot go outside. At the same time, it can stimulate the calcium channels.
So, calcium can enter into the beta cells, resulting in the depolarization. Similarly, it can stimulate the sodium channels, resulting in the entry of sodium. By all of these actions, beta cells are depolarized, resulting in the release of insulin from the beta cells. In this way, semaglutide can increase the insulin secretion from the beta cells, thereby it can reduce the blood glucose levels. Similarly, this drug can also increase the glucogon secretion, which reduce the glucose levels.
And this drug can also act on the brain, thereby it can reduce the appetite, leading to a significant reduction in the body weight. Now, let us the precautions of this drug. One of the important precaution of semaglutide is that this drug can act on the pancreas. So it can produce some pancreatitis as one of the important side effect. So in those patients with any history of pancreatitis, this drug should be carefully given.
And during the treatment, if any symptoms such as severe abdominal pain, nausea and vomiting, unexpected weight loss, all this should be carefully monitored. All this may indicate development of pancreatitis. So in such patients, this hemoglobite should be carefully given. Similarly, this drug can increase the risk of diabetic retinopathy. Normally, the excessive glucose levels may result in the diabetic retinopathy.
So in such patients, semaglutide can further increase the risk, even it is going to reduce the glucose levels. But the risk of diabetic retinopathy is increased by semaglotide. So in the diabetic patients with already developed diabetic retinopathy, this drug should not be used. Since this drug is going to reduce the glucose levels, it can produce hypoglycemia. So some weakness can be observed in the patients and this may further increase by other drugs like insulin secretogox.
For instance, sulfurias can act on beta cells and they also increase the secretion of insulin from the beta cells. So this insulin again produce hypoglycemia. So when this semaglotide is combined with insulin secretogox, like sulfanalurias.
this combination may produce significant hypoglycemia. Similarly, insulin preparations can also increase the hypoglycemia produced by semaglotide. So, when these drugs are combined with this semaglotide, care should be taken to reduce the risk of severe hypoglycemia within the patients.
