Overview:
Linagliptin is widely advised for patients suffering from type 2 diabetes mellitus.In 2011, the FDA (Food and Drug Administration) endorsed and sanctioned using Linagliptin to tackle high blood sugar levels in patients with type 2 diabetes mellitus. It can be used as a single drug therapy or incorporated into combination therapy, where Linagliptin is given in conjunction with other potent blood sugar-lowering medicines. It goes even better for patients with compromised kidney and liver function and eliminates the need for dose modifications.
Drug Group:
Linagliptin pertains to a specific category under the antidiabetic group - dipeptidyl peptidase-4 (DPP-4) inhibitors. It possesses a district mechanism in bringing down the blood sugar proportion.
Available Doses and Dosage Forms:
Dosage Forms: Linagliptin is marketed in tablet form only. The FDA has authorized no other dosage forms for type 2 diabetes mellitus patients. It is also made available as combination tablets with distinct proportions of Metformin or Empagliflozin.
Available Doses: It is manufactured and circulated in five-milligram doses.
For Patients:
What Is Diabetes?
Diabetes is a familiar and widely encountered disease with a high prevalence rate. It is a slow-paced condition, which appears to be less alarming and concerning in the initial stages, but on the go, it completely wrecks up the vital organ systems in the body. It develops when the body has trouble managing the blood sugar level within healthy and normal limits.
The blood sugar level is balanced by specific hormones called insulin and glucagon. Insulin gets triggered when the blood gets overloaded with sugar. Immediately after the food is consumed, it is acted upon by specific enzymes and juices in the stomach. The food particles get broken down into simple compounds, including sugar molecules, easily taken up from the intestine. The sudden influx of these sugar molecules into the circulation enhances the blood sugar level and brings insulin into action. Insulin works to bring down the sugar level and help the body re-establish the sugar balance in the blood. But in diabetes, the normal mechanism of blood sugar maintenance gets impaired, which is reflected in the form of a persistent hike in the blood sugar proportion. There are two distinct types of diabetes - type 1 and type 2.
Type 1 diabetes develops due to a decline in the number of cells concerned with insulin production, which is believed to be an immune-mediated condition.
While in type 2, the body's ability to produce insulin declines, or the insulin hormone itself fails to respond to the enhanced sugar level in the blood. Hypoglycemic medicines like Linagliptin are employed for dealing with type 2 and are not fruitful in type 1.
Type 1 diabetic patients experience unexplainable thirst and repeated urination. In addition, the person elicits constant tiredness and worn-out feeling. Despite frequent hunger, there will be a considerable decline in the person's body weight. Small injuries or wounds take a long time to heal and persist in active form (delayed wound healing) for extended periods.
How Does Linagliptin Work?
Linagliptin is a highly efficacious antidiabetic medicine that blocks a specific enzyme called dipeptidyl peptidase-4. DPP-4 is concerned with the deactivation and disabling of certain sugar-level-boosting compounds and thereby aids in bringing down the concentration of sugar in the blood. Linagliptin interferes with the action of DPP-4 and impedes its interaction with the sugar-level-boosting compound. As a result, the sugar level rises further, evoking insulin release (released into the bloodstream). The blood's surplus sugar level more or less influences insulin liberation. So, Linagliptin employs this technique to potentiate insulin liberation, thereby tackling the blood sugar level.
What Is the Dosage of Linagliptin?
A daily dosage of five milligrams of Linagliptin tablet is the indicated dosage regimen for patients who are identified with type 2 diabetes mellitus. Linagliptin can only be purchased from registered pharmacies with a written prescription from the doctor. Studies have shown that Linagliptin is safer even in the presence of kidney and liver conditions, whereas most other drugs entail either drug withdrawal or dose modification.
How Effective Is Linagliptin?
The effectiveness and potential of Linagliptin in dealing with type 2 diabetes mellitus is proven. Clinical trials were conducted to establish the potency and to assess the likelihood of complications associated with Linagliptin. The trials finally ended up flagging a green signal for Linagliptin. Prompt therapy with Linagliptin elicits a remarkable collapse in the glycosylated hemoglobin (hemoglobin molecules coupled with sugar molecules). It goes well with other antidiabetic medicines like Metformin upon dose alteration, which extends its application as a combination drug. The precipitation of hypoglycemia (collapse in the sugar level) is a known side effect concerning most antidiabetic medicines. However, studies have revealed that the tendency to precipitate hypoglycemia is considerably low in the case of Linagliptin compared to other antidiabetic medicines.
What Are the Things to Inform the Doctor Before Taking the Drug?
A prior allergic encounter with Linagliptin exposure should be discussed with the doctor before initiating the treatment regime using Linagliptin. Hyperreactivity to any drugs in the same class should also be given attention and properly communicated with the doctor.
The doctors should be made aware of all the underlying conditions that the person suffers from or previously suffered to analyze the health status and the potential risk of administering the medicine to the person. Apart from the medical history, all the details regarding the medications, even nutritional supplements or Ayurveda products, should be discussed with the doctor to check for unwanted interaction with Linagliptin.
Women who are planning to conceive or who are already pregnant should keep their doctors aware of conception. Certain tablet intake during conception can pose risks to the developing fetus (child in the womb), though Linagliptin is not proven to have such an association. However, to be safer, it is better not to administer any tablet during pregnancy unless the mother's health condition dictates it. The doctor will analyze the condition, considering the child's and mother's health, and decide accordingly. Lactating women should always inform their doctor about their breastfeeding status to check for unwanted reactions in the breastfed baby.
How Is Linagliptin Administered?
Linagliptin is manufactured and made available in tablet form, intended to be taken by mouth and a glass of water. It is advised to take the medicine per the doctor's guidelines and instructions to check overdosing and under-dosing issues. The pill should be taken as a whole without splitting or shattering it.
What Are the Side Effects of Linagliptin?
The incidence of side effects in association with Linagliptin is considerably low. Studies have reported hypoglycemia after Linagliptin therapy, particularly when taken with other blood sugar-lowering drugs. Furthermore, enhanced liberation of the lipase enzyme (act on fat molecules) is also noted with Linagliptin. Less frequently, nasopharyngitis (common cold) and bronchial hyperreactivity (exaggerated collapse of the air passage in response to stimuli) are encountered in patients undergoing Linagliptin therapy. Digestive problems like constipation and skin issues like rashes were also demonstrated in certain patients.
Dietary Considerations:
No specific dietary considerations need to be followed while on Linagliptin therapy. The intake of food does not interfere with the Linagliptin's action. Hence, food intake is not restricted according to the timing of medicine consumption, unlike other antidiabetic medicines. However, the diet plan should be formulated per the patient's sugar level to benefit from Linagliptin therapy.
Missed Dose:
The patient may sometimes miss taking the pill at the specified time. In such cases, patients can take the pill once they become aware of it. However, if the patient realizes the missed dose quite late when it is time for a subsequent dose, it is advised to skip the forgotten dose. Taking two pills to counterbalance the missed one can precipitate unwanted effects like an immediate collapse in blood sugar level.
Overdose:
Overdose studies were conducted with 600 milligrams of Linagliptin administered as a single dose in individuals who were tested to be healthy. Studies could not expose any overdose issues in those individuals. However, clearing the medicine from the stomach is the first-line approach during overdosage. Poison control centers should be immediately contacted to address the overdose issues, and necessary medical interventions should be employed to tackle life-threatening complications.
Storage:
Linagliptin is marketed either in blister packaging or in dispenser bottles. The pills can be safely kept in the packing until consumption, provided the storage temperature should be within the range of 15 to 30 degrees Celsius. Exposure to extreme temperature, light, and heat can influence the stability of the ingredients in the pill, which in turn impacts the drug's action.
For Doctors:
Indication:
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Type 2 diabetes mellitus.
Dose:
The daily dose of five milligrams of Linagliptin is the proposed dosage for type 2 diabetes mellitus. Prompt results in the glycemic status can be achieved when the pill intake is coupled with dietary changes and physical exercises.
Dosing Considerations:
Certain considerations in the dose should be advised when Linagliptin is incorporated with insulin secretagogues as part of combination therapy. The insulin secretagogue concentration and proportion should be minimized to check the development of hypoglycemic attacks. Though Linagliptin is proven to be effective for type 2 diabetes mellitus, its use should not be extended to diabetic ketoacidosis or type 1 diabetes mellitus. Linagliptin does not work well for these two conditions.
What Are the Pharmacological Aspects of Linagliptin?
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Mechanism: Being a potent DPP-4 inhibitor, Linagliptin effectively impedes the activities of DPP-4. Dipeptidyl peptidase-4 (DPP-4) is associated with the breaking down of incretin hormones. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptides are the chief incretin hormones that can exponentially elevate glucose levels. Linagliptin exerts its influence through dipeptidyl peptidase-4 by interacting with the DPP-4 molecule. The drug molecule blocks the DPP-4 by attaching to it, boosting the incretin hormone level in the blood. The elevated glucose concentration enhances insulin's liberation as it is dose-dependent.
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Pharmacodynamics: Besides the DPP-4 inhibition, Linagliptin effectively manipulates glucagon liberation and eventually lowers glucagon levels. The interaction of Linagliptin with DPP-4 molecules is reversible. However, the attachment is specific and spares other DPP molecules like DPP-9 and DPP-8.
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Pharmacokinetics: Only 30 percent of the orally administered Linagliptin gets into circulation and is available for action. It takes one hour and 30 minutes to attain the utmost concentration in the blood. Linagliptin attaches to the DPP-4 molecules, and once all the DPP molecules are overloaded with Linagliptin, further distribution of Linagliptin is carried out by plasma proteins. Unlike other drug molecules, Linagliptin is quite resistant to metabolism by liver enzymes. An insignificant proportion of Linagliptin undergoes enzymatic breakdown into inert molecules. The enterohepatic system is the prime route concerned with Linagliptin removal from the body, while a smaller proportion moves out of the body via urine.
Toxicity:
Nonclinical studies for assessing the toxicity issues failed to elicit a remarkable impact on the animal's fertility. However, carcinogenic changes were reported with a considerably higher dose of Linagliptin. No reliable information is available concerning the toxicity issues in the human population.
Clinical Studies:
Clinical studies have proven the potency of Linagliptin in monotherapy and combination therapy for dealing with type 2 diabetes mellitus. The studies were conducted on a randomized population group of known type 2 diabetes mellitus patients. The effectiveness was assessed by comparing the glycemic control with the placebo population.
What Are the Contraindications of Linagliptin?
There are no significant contraindications for Linagliptin. However, Linagliptin is contraindicated for individuals with known allergies to Linagliptin. Allergic response should be assessed in doubtful patients before regular drug administration. Allergic reactions can be manifested in the form of urticaria, facial puffiness, and breathing troubles.
Warnings and Precautions:
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Simultaneous Intake With Insulin Secretagogue: Patients should be adequately instructed and forewarned about the possibility of hypoglycemic events upon simultaneous exposure to Linagliptin and insulin secretagogue. It is often tackled by altering the dosage of the insulin secretagogue by keeping its dosage on the lower side to check the likelihood of hypoglycemia. In addition to insulin secretagogues, insulin should not be combined with Linagliptin to enhance glycemic control. In such cases, the insulin dose should be restricted to a minimal dose.
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Type 1 Diabetes Mellitus: Linagliptin is unsuitable for patients with type 1 diabetes mellitus. Only type 2 diabetes mellitus patients benefit from Linagliptin therapy.
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Diabetic Ketoacidosis: Similarly, Linagliptin is not advised to be employed for diabetic patients who are diagnosed with diabetic ketoacidosis, which is a grave condition that entails immediate medical attention.
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Acute Pancreatitis: Linagliptin may enhance the risk of acute pancreatitis in susceptible individuals. It is seen following long-term exposure to Linagliptin. Hence, keeping the patients cautioned about pancreatitis and its early manifestations is vital. Periodic assessment of the pancreas helps track developing pancreatitis and timely withdrawal of Linagliptin, which is crucial to check the disease progression.
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Bullous Pemphigoid: Rarely, Linagliptin may precipitate bullous pemphigoid, which demands cessation of Linagliptin therapy.
What Are the Drug Interactions of Linagliptin?
Linagliptin may interact with certain other drugs, which may impact the effectiveness of one or both. Simultaneous intake of Linagliptin and cytochrome 34A inducer drugs impairs Linagliptin's effectiveness.
Linagliptin and Rifampicin, when taken together, significantly collapses the utmost concentration of Linagliptin and thus creates a check on the potency of Linagliptin. Likewise, P-glycoprotein inducer medicines also elicit a similar kind of interaction with Linagliptin, and when given together, it can gear down the potency of Linagliptin.
Specific Considerations:
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Linagliptin During Pregnancy: Linagliptin falls under category B for pregnant women. The lack of reliable human study reports makes it difficult to arrive at a definite conclusion regarding using Linagliptin during conception. However, animal studies at exceptionally high doses elicited a setback in fetal growth. Hence, Linagliptin is advised only after considering the pregnant woman's medicine needs.
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Linagliptin During Breastfeeding: The fact concerning the discharge of Linagliptin via breastmilk still needs to be clarified and more specific. Animal studies have proven the presence of Linagliptin in their breast milk. However, animal study reports are inconclusive for human use. Hence, Linagliptin prescription for lactating mothers entails caution.
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Linagliptin for the Geriatric Population: Clinical study reports favored using Linagliptin in the geriatric population, as it demonstrated analogous effects without much appreciable impairment in drug effectivity.
