Liraglutide

Uses

Liraglutide is used for an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease

Liraglutide is also used to associated treatment for these conditions: BMI >30 kg/m2, Cardiovascular Risk Reduction, Type 2 Diabetes Mellitus

How Liraglutide works

Liraglutide is an acylated synthetic glucagon-like peptide-1 analog. Liraglutide is an agonist of the glucagon-like peptide-1 receptor which is coupled to adenylate cyclase. The increase in cyclic AMP stimulates the glucose dependant release of insulin, inhibits the glucose dependant release of glucagon, and slows gastric emptying to increase control of blood sugar.

Dosage

Liraglutide dosage

Inject Liraglutide subcutaneously once-daily at any time of day, independently of meals. Initiate Liraglutide with a dose of 0.6 mg per day for one week. The 0.6 mg dose is a starting dose intended to reduce gastrointestinalsymptoms during initial titration, and is not effective for glycemic control. After one week at 0.6 mg per day, the dose should be increased to 1.2 mg. If the 1.2 mg dose does not result in acceptable glycemic control, the dose can be increased to 1.8 mg. If a dose is missed, resume the once-daily regimen as prescribed with the next scheduled dose. Do not administer an extra dose or increase in dose to make up for the missed dose.

If more than 3 days have elapsed since the last Liraglutide dose, reinitiate Liraglutide at 0.6 mg to mitigate any gastrointestinal symptoms associated with reinitiation of treatment. Upon reinitiation, Liraglutide should be titrated at the discretion of the prescriber.

• Inspect visually prior to each injection. Only use if solution is clear, colorless, and contains no particles.
• Inject Liraglutide subcutaneously in the abdomen, thigh or upper arm. No dose adjustment is needed if changing the injection site and/or timing.
• When using Liraglutide with insulin, administer as separate injections. Never mix.
• It is acceptable to inject Liraglutide and insulin in the same body region but the injections should not be adjacent to each other.

Side Effects

Nausea, diarrhoea, vomiting, constipation, headache, dizziness, upper resp tract infection, influenza, sinusitis, nasopharyngitis, UTI, back pain, dehydration. Increased blood calcitonin, goitre, and thyroid neoplasms.

Toxicity

There is no clinical significance of race or ethnicity on the safety or efficacy of liraglutide. Geriatric patients do not experience clinically significant differences in pharmacokinetics though patients at an especially advanced age may be more susceptible to adverse effects. Female patients have reduced clearance of liraglutide but no dose adjustment is necessary. The risk and benefit of liraglutide in pregnancy must be weighed before prescribing. In animal studies, liraglutide is associated with an increased risk of embryonic death and fetal abnormalities though an HbA1c > 7 is also associated with a 20-25% risk of birth defects. In animal studies, liraglutide is present in the milk of lactating rats at half the plasma concentration of the mother but these results may not translate to humans. Because it is not known if liraglutide is present in breast milk and the effects on infants are also unknown, the risk and benefit of liraglutide in breastfeeding must be considered before prescribing. Liraglutide was shown to be safe and effective in patients up to 160kg in weight but has not been studied in patients at a higher weight. A patient's weight significantly affects the pharmacokinetics of liraglutide. Liraglutide has not been investigated for use in pediatric patients. No dosage adjustments are necessary in patients with renal impairment but studies have not been performed in patients with end stage renal disease. There are no recommendations on dosage adjustment in patients with hepatic impairment, though caution should still be exercised when prescribing to this population.

Precaution

Patients with history of pancreatitis or alcoholism, inflammatory bowel disease, diabetic gastroparesis, pre-existing thyroid disease. Renal impairment. Pregnancy and lactation.

Interaction

Increased risk of hypoglycaemia when used w/ insulin secretagogues (e.g. sulfonylurea, meglitinide). May affect absorption of concomitantly administered oral drugs due to slow gastric emptying.

Food Interaction

• Take with or without food.

[Moderate] MONITOR: Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists delay gastric emptying, which may impact the absorption of concomitantly administered oral medications.

Mild to moderate decreases in plasma concentrations of coadministered drugs have been demonstrated in pharmacokinetic studies for some GLP-1 receptor agonists (e.g., exenatide, lixisenatide), but not others.

The impact of dual GLP-1 and GIP receptor agonist tirzepatide on gastric emptying was reported to be greatest after a single dose of 5 mg but diminished after subsequent doses.

According to the prescribing information, liraglutide did not affect the absorption of several orally administered drugs to any clinically significant extent, including acetaminophen, atorvastatin, digoxin, griseofulvin, lisinopril, and an oral contraceptive containing ethinyl estradiol-levonorgestrel.

Likewise, no clinically relevant effect on absorption was observed for concomitantly administered oral drugs studied with albiglutide (digoxin, ethinyl estradiol-norethindrone, simvastatin, warfarin), dulaglutide (acetaminophen, atorvastatin, digoxin, ethinyl estradiol-norelgestromin, lisinopril, metformin, metoprolol, sitagliptin, warfarin), or semaglutide (atorvastatin, digoxin, ethinyl estradiol-levonorgestrel, metformin, warfarin).

In addition, coadministration of acetaminophen after a first dose of tirzepatide 5 mg reduced the acetaminophen peak plasma concentration (Cmax) by 50% and delayed its median time to peak plasma concentration (Tmax) by 1 hour, but no significant impact on Cmax and Tmax was observed after coadministration at week 4, and the overall exposure of acetaminophen was unaffected.

Nevertheless, potential clinical impact on other oral medications cannot be ruled out, particularly those with a narrow therapeutic index or low bioavailability, those that depend on threshold concentrations for efficacy (e.g., antibiotics), and those that require rapid gastrointestinal absorption (e.g., hypnotics, analgesics).
br> MANAGEMENT: Pharmacologic response to concomitantly administered oral medications should be monitored more closely following the initiation or discontinuation of treatment with a GLP-1 receptor agonist or a dual GLP-1 and GIP receptor agonist.

Liraglutide Alcohol interaction

[Moderate] GENERALLY AVOID:

Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes.

Hypoglycemia most frequently occurs during acute consumption of alcohol.

Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise.

The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia.

Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion.

By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia.

[Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes.

A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis.

Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan.

Alcohol should not be consumed on an empty stomach or following exercise.

Liraglutide Drug Interaction

Moderate: insulin glargine, lithium, levothyroxineMinor: atorvastatinUnknown: pioglitazone, aspirin, celecoxib, ubiquinone, rosuvastatin, duloxetine, omega-3 polyunsaturated fatty acids, sitagliptin, levocarnitine, escitalopram, pregabalin, metoprolol, esomeprazole, cyanocobalamin, ergocalciferol, cholecalciferol

Liraglutide Disease Interaction

Major: pancreatitis, thyroid carcinoma, depressionModerate: renal dysfunction, cardiovascular disease

Volume of Distribution

13L.

Elimination Route

Bioavailability of liraglutide after subcutaneous injection is approximately 55% and maximum concentrations are reached after 11.7 hours.

Half Life

Terminal half life of 13 hours.

Clearance

1.2L/h.

Elimination Route

6% excreted in urine and 5% excreted in feces.

Pregnancy & Breastfeeding use

Pregnancy category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Personal or family history of medullary thyroid carcinoma (MTC). Patients with multiple endocrine neoplasia syndrome type 2; type 1 DM or diabetic ketoacidosis. Liraglutide is not a substitute for insulin.

Acute Overdose

Overdoses have been reported in clinical trials and post-marketing use of Liraglutide. Effects have included severe nausea and severe vomiting. In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms.

Storage Condition

Store between 2-8° C. Do not freeze. After initial use, it can be stored between 15-30° C for 30 days. Protect from heat and light.

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