Saxagliptin (Onglyza) is a DPP-IV inhibitor that is used to treat patients with diabetes mellitus type 2.

It increases the half-life of endogenous incretins and causes glucose-dependent insulin secretion.

Saxagliptin (Onglyza) Uses:

• Diabetes mellitus, type 2:

  • It is used as adjunctive therapy to diet and exercise for improving glycemic control in adults with type 2 diabetes mellitus as monotherapy or in combination therapy.

Saxagliptin (Onglyza) Dose in Adults

Saxagliptin (Onglyza) Dose in the treatment of type 2 Diabetes mellitus:

• Oral: 2.5 to 5 mg OD

Concomitant use with strong CYP3A4/5 inhibitors

• (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin):
  • 5 mg OD

• Concomitant use with insulin or insulin secretagogues:

  • May require reducing the dose of insulin or insulin secretagogues (eg, sulfonylureas).

Use in Children:

Not indicated. 

Pregnancy Risk Category: B

• Poorly controlled diabetes can lead to adverse maternal and fetal outcomes. Preeclampsia and diabetic ketoacidosis are all possible.
• Preventing these negative outcomes is possible by keeping maternal blood glucose and HbA levels as close as possible to their target levels before conception and throughout pregnancy.
• For the treatment of diabetes during pregnancy, agents other than saxagliptin should be considered.

Use of Saxagliptin during lactation

• It is unknown whether breast milk contains saxagliptin.
• According to the manufacturer, there are some things you should consider when considering breastfeeding during therapy.
  • The risk of infant exposure
  • Breastfeeding is good for the infant
  • The mother reaps the benefits of the treatment

Dose in Kidney Disease:

• eGFR >=45mL/minute/1.73m 2Osage adjustment is not required.
• eGFR = 45 mL/minute/1.73 25 mg OD.
• ESRD requires hemodialysis5 mg OD after dialysis
• Peritoneal dialysisThere were no dosage adjustments in the labeling of the manufacturer (has not been tested).

Dose in Liver disease:

• Mild to severe impairment: Dosage adjustment not necessary.

Less Common Side Effects of Saxagliptin (Onglyza):

• Cardiovascular:

  • Peripheral Edema

• Central Nervous System:

  • Headache

• Endocrine & Metabolic:

  • Hypoglycemia

• Genitourinary:

  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Lymphocytopenia
  • Thrombocytopenia

• Hypersensitivity:

  • Hypersensitivity Reaction

Contraindications to Saxagliptin (Onglyza):

Canadian labeling: Additional contraindications:

• Hypersensitivity, including anaphylaxis and angioedema, & exfoliative conditions of the skin (to saxagliptin)
• Hypersensitivity to DPP-4 Inhibitors
• Diabetic ketoacidosis
• Precoma/Diabetic coma
• Type 1 diabetes mellitus

Warnings and precautions

• Arthralgia

  • DPP-IV inhibitor can cause severe and debilitating arthralgia. It may appear within a few days to years after treatment began.
  • The symptoms may disappear if therapy is stopped. If DPPIV inhibitor therapy are resumed, symptoms may recur.

• Bullous pemphigoid

  • Bullous pemphigoid can occur when DPP-4 inhibitor is used.
  • Topical or systemic immunosuppressive therapy may need to be administered. It may also resolve with discontinuation DPP-4 inhibitor therapy.
  • Report any blisters or erosions to your doctor immediately. If you suspect bullous pemphigoid, discontinue treatment and consult a dermatologist.

• Hematologic:

  • A decrease in lymphocyte count (dose-related) was observed.
  • The clinical significance of this finding is not known. Patients with persistent or unusual infections should monitor their lymphocyte count.

• Hypersensitivity reactions

  • Anaphylaxis, exfoliative dermatologic reactions, and angioedema have all been reported as hypersensitivity reactions. If you experience severe symptoms, discontinue use.
  • These events usually occur within the first three month of starting therapy.
  • They may also occur after the initial dose. If you have experienced angioedema from the use of DPP-IV inhibitors, be cautious.

• Pancreatitis

  • Acute pancreatitis may occur. You should monitor for symptoms and signs of pancreatitis.
  • If there are suspicions, the drug should immediately be stopped. Patients with a history or risk factors for pancreatitis should be treated with caution.

• Bariatric surgery

  • Absorption altered:
    • The gastric bypass and Sleeve Gastrectomy Surgery can cause anatomical and transit changes that may affect absorption.
  • Exposure to Glucagon-like peptide-1 and its therapeutic efficacy
    • You should monitor your symptoms for pancreatitis.
    • Gastric bypass and Sleeve Gastrectomy may increase endogenous glucagon-like Peptide-1 secretion.

• Heart Failure:

  • In a multi-center, randomized, double-blind placebo-controlled trial, heart failure (HF), which required hospitalization, was reported in type 2 diabetes patients who had a history of or are at high risk for cardiovascular events. Patients with preexisting renal impairment or heart failure were at higher risk.
  • In an ambulatory setting with lower baseline cardiovascular risk factors, a population-based retrospective study did not show an increase in the risk of patients taking saxagliptin relative to other agents (eg sitagliptin or pioglitazone),
  • Therapy should be closely monitored for signs and symptoms of heart disease. If the condition worsens, therapy should be stopped immediately.
  • According to the AHA's scientific statement, saxagliptin may be an agent that can exacerbate the underlying myocardial dysfunction (magnitude major).
  • The ADA recommends that patients with HF should not use saxagliptin.

• Renal impairment

  • Patients with moderate or severe renal dysfunction (eGFR 45 mL/minute/1.73 m) and end-stage renal disease, (ESRD), should be cautious. Dosing adjustments may be necessary.

Saxagliptin: Drug Interaction

Monitoring parameters:

• Plasma glucose
• HbA (at minimum 6 months in patients with stable glycemic control who are meeting their treatment goals; 3 months in patients not meeting treatment goal or who need therapy change [ADA 2019,]).
• Renal function (before and periodically after therapy is initiated)
• If there is an unusual or persistent infection, the lymphocyte count will be taken.
• Signs/symptoms of heart failure and/or pancreatitis.

How to administer Saxagliptin?

Oral: May administer without relation to a meal. Should be swallowed as a whole; do not split or cut tablets. 

Mechanism of action of Saxagliptin (Onglyza):

• Saxagliptin inhibits dipeptidyl-peptidase IV enzyme (DPP IV), resulting in long active incretin levels. 
• Incretin hormones, such as glucagon-like protein-1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP], regulate glucose homeostasis.
• They increase insulin synthesis and release from pancreatic beta cells while decreasing the secretion from pancreatic alpha cell glucagon.
• A decrease in glucagon secretion leads to a decrease of liver glucose production. 
• Normal physiological circumstances see the liver release incretin hormones throughout a day.
• These levels increase after meals. The DPP-IV enzyme causes rapid inactivation.

Duration: 24 hours

Protein binding: Negligible

Metabolism: Occurs in the liver via CYP3A4/5 to 5-hydroxy saxagliptin (active; ~50% potency of the parent compound)

Half-life elimination: Saxagliptin: 2.5 hours; 5-hydroxy saxagliptin: 3.1 hours

Time to peak, plasma: Saxagliptin: 2 hours; 5-hydroxy saxagliptin: 4 hours

Excretion:

• Urine (75%, 24% of the total dose as saxagliptin, 36% of the total dose as 5-hydroxy saxagliptin)
• Feces

International Brand Names of Saxagliptin:

• Formigliptin
• Glipitrose
• Glyza
• Ongliza
• Onglyza
• Sixtin

Saxagliptin Brand Names in Pakistan:

No Brands Available in Pakistan.