New Drug Approved for Diabetes.

USFDA approved Adlyxin (lixisenatide), a once-daily injection to improve glycemic control (blood sugar levels), along with diet and exercise, in adults with type 2 diabetes.

Mechanism of action

• Lixisenatide is a selective GLP-1 receptor agonist.
• The GLP-1 receptor is the target for native GLP-1, an endogenous incretin hormone that potentiates glucose-dependent insulin secretion from the pancreatic beta cells.
• Lixisenatide action is mediated via a specific interaction with GLP-1 receptors, leading to an increase in intracellular cyclic adenosine monophosphate (cAMP).
• Lixisenatide stimulates insulin secretion when blood glucose is increased but not at normoglycaemia, which limits the risk of hypoglycaemia.
• In parallel, glucagon secretion is suppressed. In case of hypoglycaemia, the rescue mechanism of glucagon secretion is preserved. Lixisenatide slows gastric emptying thereby reducing the rate at which meal-derived glucose appears in the circulation.

Therapeutic indications

Lixisenatide is indicated for the treatment of adults with type 2 diabetes mellitus to achieve glycaemic control in combination with oral glucose-lowering medicinal products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycaemic control.

Dosage and administration:

• Lixisenatide is to be injected subcutaneously in the thigh, abdomen or upper arm.
• Starting dose: dosing is initiated at 10 mcg Lixisenatide once daily for 14 days.
• Maintenance dose: a fixed maintenance dose of 20 mcg Lixisenatide once daily is started on Day 15.
• Lixisenatide 20 micrograms solution for injection is available for the maintenance dose.
• Lixisenatide is administered once daily, within the hour prior to any meal of the day, preferably the same meal each day.
• If a dose of Lyxumia is missed, it should be injected within the hour prior to the next meal.
• The clinical experience in patients ≥75 years is limited. Limited therapeutic experience in patients with moderate renal impairment (creatinine clearance: 30-50 ml/min) and Lixisenatide should be used with caution in this population.
• There is no therapeutic experience in patients with severe renal impairment (creatinine clearance less than 30 ml/min) or end-stage renal disease and therefore, it is not recommended to use Lixisenatide in these populations.
• The safety and efficacy of Lixisenatide in children and adolescents less than 18 years of age have not yet been established.

SAFETY & EFFICACY

• The drug’s safety and effectiveness were evaluated in 10 clinical trials that enrolled 5,400 patients with type 2 diabetes.
• In these trials, Adlyxin was evaluated both as a standalone therapy and in combination with other FDA-approved diabetic medications, including metformin, sulfonylureas, pioglitazone and basal insulin.
• Use of Adlyxin improved hemoglobin A1c levels (a measure of blood sugar levels) in these trials.
• In addition, more than 6,000 patients with type 2 diabetes at risk for atherosclerotic cardiovascular disease were treated with either Adlyxin or a placebo in a cardiovascular outcomes trial. Use of Adlyxin did not increase the risk of cardiovascular adverse events in these patients.

Adverse reactions:

• Very common: Hypoglycaemia (in combination with a sulphonylurea and / or a basal insulin). Headache. Nausea, vomiting & diarrhoea; These tend to be mostly mild and transient during the first 3 weeks after starting treatment. Thereafter, they progressively decrease during the following weeks.
• Common: Influenza, upper respiratory tract infection, cystitis & viral infection. Hypoglycaemia (in combination with metformin alone). Dizziness, somnolence, dyspepsia, back pain, injection site pruritus.
• Uncommon: Anaphylactic reaction and urticaria. Please consult the Summary of Product Characteristics in relation to other adverse reactions.

The FDA is requiring the following post-marketing studies for Adlyxin:

• Clinical studies to evaluate dosing, efficacy and safety in pediatric patients.
• A study evaluating the immunogenicity of lixisenatide.

Adlyxin is manufactured by Sanofi-Aventis U.S. LLC, of Bridgewater, New Jersey.

References:

1. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002445/WC500140401.pdf
2. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm513602.htm
3. Image Source- http://img.medscape.com/slide/migrated/editorial/cmecircle/2006/6013/images/drucker/slide022.gif