Onglyza (Saxagliptin)

What Is Onglyza and What Is It Used For?

Onglyza (saxagliptin) is an oral diabetes medication that belongs to the dipeptidyl peptidase-4 (DPP-4) inhibitor class. It is used to treat type 2 diabetes in adults aged 18 years and older when diet, exercise, and other oral antidiabetic medications do not provide adequate blood sugar control.

Saxagliptin works by inhibiting the enzyme DPP-4, which normally breaks down the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These incretin hormones are released from the gut after eating and play a crucial role in blood sugar regulation. GLP-1 stimulates insulin secretion from the pancreatic beta cells and suppresses glucagon release from the alpha cells, both in a glucose-dependent manner. By preventing the rapid degradation of these hormones, saxagliptin extends their activity, leading to improved blood sugar control after meals.

A key clinical advantage of this mechanism is that the insulin-stimulating effect of saxagliptin is glucose-dependent. This means that it primarily enhances insulin secretion when blood sugar levels are elevated (such as after a meal) and has minimal effect when blood sugar is normal or low. As a result, the risk of hypoglycaemia (dangerously low blood sugar) is substantially lower with DPP-4 inhibitors compared to sulphonylureas or insulin, particularly when used as monotherapy or in combination with metformin.

Onglyza is approved for use as monotherapy (when metformin is inappropriate due to intolerance or contraindication) or as add-on combination therapy with metformin, sulphonylureas, thiazolidinediones, or insulin. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) consensus guidelines position DPP-4 inhibitors as a second-line option after metformin, particularly for patients where avoiding hypoglycaemia and weight gain are important considerations.

It is essential to understand that Onglyza is not a substitute for insulin in patients who require it. The medication does not work in type 1 diabetes (where the body produces no insulin) and should never be used to treat diabetic ketoacidosis. Patients should continue following the dietary and lifestyle recommendations provided by their healthcare team while taking Onglyza.

What Should You Know Before Taking Onglyza?

Before starting Onglyza, inform your doctor about all your medical conditions, especially any history of heart failure, pancreatitis, kidney or liver disease, and all other medications you are taking. Onglyza must not be used in type 1 diabetes or diabetic ketoacidosis.

Contraindications

You should not take Onglyza if any of the following apply to you:

• Allergy to saxagliptin or any of the inactive ingredients in Onglyza – symptoms of an allergic reaction may include rash, hives, or swelling of the face, lips, tongue, or throat
• Serious allergic reaction to any DPP-4 inhibitor – if you have previously experienced a severe hypersensitivity reaction (such as anaphylaxis or angioedema) to another gliptin, you should not take Onglyza
• Type 1 diabetes – your body does not produce insulin, and Onglyza cannot replace insulin therapy
• Diabetic ketoacidosis – a serious complication of diabetes characterised by high blood sugar, rapid weight loss, nausea, or vomiting. This condition requires urgent treatment with insulin, not oral medications

Warnings and Precautions

Talk to your doctor or pharmacist before taking Onglyza if you have or have had any of the following conditions:

• Heart failure or risk factors for heart failure – the SAVOR-TIMI 53 cardiovascular outcomes trial demonstrated a statistically significant increase in hospitalisation for heart failure in patients taking saxagliptin compared to placebo. Your doctor will inform you about the signs and symptoms of heart failure. Seek immediate medical attention if you develop increasing breathlessness, rapid unexplained weight gain, or swelling of the feet (pedal oedema)
• History of pancreatitis – there have been post-marketing reports of acute pancreatitis in patients taking DPP-4 inhibitors. If you experience severe, persistent abdominal pain that may radiate to the back, accompanied by nausea and vomiting, stop taking Onglyza and contact your doctor immediately
• Kidney impairment – if you have reduced kidney function, your doctor will prescribe the lower 2.5 mg dose. If you are on haemodialysis, Onglyza is not recommended
• Moderate to severe liver disease – Onglyza should be used with caution in moderate hepatic impairment and is not recommended in severe hepatic impairment due to limited clinical data
• Immunocompromised state – if you have a condition that weakens your immune system (such as HIV/AIDS) or are taking immunosuppressive medicines (such as those used after organ transplantation), tell your doctor, as a small reduction in lymphocyte counts has been observed with saxagliptin
• Taking insulin or sulphonylureas – when Onglyza is added to insulin or a sulphonylurea, the risk of hypoglycaemia increases. Your doctor may need to reduce the dose of your insulin or sulphonylurea to minimise this risk

Skin reactions: Diabetic skin lesions are a known complication of diabetes. Rash has been reported with Onglyza and other DPP-4 inhibitors. Follow your doctor's recommendations for skin and foot care. Contact your doctor if you develop skin blistering, as this may be a sign of bullous pemfigoid, a condition that may require you to stop taking Onglyza.

Use in Children and Adolescents

Onglyza is not recommended for children and adolescents under 18 years of age. The safety and efficacy of saxagliptin have not been established in this age group. Type 2 diabetes in children is typically managed with metformin and/or insulin under specialist paediatric endocrinology supervision.

Pregnancy and Breastfeeding

Onglyza should not be used during pregnancy. The safety of saxagliptin in pregnant women has not been established. Animal studies have not shown direct harmful effects on fertility or foetal development, but as a precaution, saxagliptin should be avoided during pregnancy. If you are pregnant, think you might be pregnant, or are planning to become pregnant, tell your doctor before taking Onglyza. Your doctor will likely switch you to insulin, which is the preferred treatment for managing diabetes during pregnancy.

It is not known whether saxagliptin passes into human breast milk. You should not take Onglyza if you are breastfeeding or planning to breastfeed. Discuss alternative treatment options with your doctor.

Driving and Operating Machinery

Do not drive or use tools or machines if you feel dizzy while taking Onglyza. Hypoglycaemia (low blood sugar) can impair your ability to drive and operate machinery, and there is a risk of hypoglycaemia if you take Onglyza in combination with medicines known to cause low blood sugar, such as insulin and sulphonylureas. If you experience symptoms of low blood sugar (shaking, sweating, anxiety, blurred vision), stop what you are doing and treat the hypoglycaemia immediately.

Important Information About Excipients

Onglyza tablets contain lactose (milk sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine. This medicine also contains less than 1 mmol sodium (23 mg) per dose, meaning it is essentially "sodium-free."

How Does Onglyza Interact with Other Drugs?

Saxagliptin is metabolised primarily by the liver enzyme CYP3A4/5. Strong CYP3A4/5 inhibitors increase saxagliptin blood levels (requiring dose reduction to 2.5 mg), while strong enzyme inducers may reduce its effectiveness. Always inform your doctor about all medications, supplements, and herbal products you are taking.

Drug interactions with saxagliptin primarily relate to its hepatic metabolism via the CYP3A4/5 enzyme pathway. Medications that inhibit this enzyme can increase saxagliptin blood concentrations, potentially increasing the risk of side effects. Conversely, medications that induce (speed up) this enzyme can reduce saxagliptin levels, potentially making it less effective at controlling blood sugar. Additionally, combining Onglyza with certain other diabetes medications increases the risk of hypoglycaemia.

Clinically Significant Interactions

Other strong CYP3A4/5 inhibitors that may require Onglyza dose reduction to 2.5 mg include itraconazole, clarithromycin, indinavir, nelfinavir, ritonavir, saquinavir, and telithromycin. Always consult your doctor before starting or stopping any medication while taking Onglyza.

What Is the Correct Dosage of Onglyza?

The recommended dose of Onglyza is 5 mg once daily for most adults. Patients with moderate to severe kidney impairment or those taking strong CYP3A4/5 inhibitors should take 2.5 mg once daily. The tablet should be swallowed whole with water and can be taken with or without food.

Always take Onglyza exactly as your doctor has prescribed. Do not change your dose without consulting your doctor first. Your doctor may prescribe Onglyza alone or together with insulin or other diabetes medications. If you are taking Onglyza in combination with other oral diabetes medicines, remember to take those medicines as instructed by your doctor to achieve the best results for your health.

Adults (Standard Dosing)

Patients with Kidney Impairment

Elderly Patients

No specific dose adjustment is required based on age alone. However, elderly patients are more likely to have reduced kidney function, so your doctor should assess renal function before prescribing and periodically during treatment. The 2.5 mg dose should be used if kidney function is moderately or severely impaired.

Patients with Liver Impairment

No dose adjustment is needed for patients with mild or moderate hepatic impairment. Onglyza is not recommended for patients with severe liver disease due to limited clinical experience in this population.

Missed Dose

If you forget to take a dose of Onglyza, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose. Do not take a double dose to compensate for a forgotten dose. Never take two doses on the same day.

Overdose

Stopping Onglyza

Continue taking Onglyza until your doctor tells you to stop. It helps keep your blood sugar under control. Do not stop taking this medicine without consulting your doctor first, as uncontrolled blood sugar can lead to serious long-term complications including damage to the eyes, kidneys, nerves, and blood vessels.

What Are the Side Effects of Onglyza?

The most common side effects vary depending on which other diabetes medication Onglyza is combined with. When used with a sulphonylurea or insulin, hypoglycaemia (low blood sugar) is very common. Other common side effects include upper respiratory infections, urinary tract infections, headache, and gastrointestinal symptoms. Serious but rare risks include pancreatitis, severe allergic reactions, and heart failure hospitalisation.

Like all medicines, Onglyza can cause side effects, although not everybody gets them. The side effect profile of saxagliptin depends significantly on which other diabetes medications it is combined with.

Side Effects When Used Alone (Monotherapy)

Side Effects When Used with Metformin

Side Effects When Used with a Sulphonylurea

Side Effects When Used with a Thiazolidinedione

Side Effects When Used with Metformin and a Sulphonylurea (Triple Therapy)

Side Effects of Unknown Frequency (All Combinations)

Some patients taking saxagliptin have experienced a small decrease in the number of a type of white blood cells called lymphocytes, shown in blood tests. This has been observed both when Onglyza is used alone and in combination. The clinical significance of this finding is not fully established, but you should inform your doctor if you develop frequent or unusual infections.

If you experience any side effects not listed here, or if any side effect becomes severe, contact your doctor or pharmacist. Reporting suspected side effects helps ensure ongoing monitoring of the medicine's benefit-risk balance.

How Should You Store Onglyza?

Store Onglyza tablets at room temperature in their original blister packaging, out of the reach and sight of children. No special storage conditions are required. Do not use after the expiry date on the packaging.

Keep Onglyza tablets in the original blister pack to protect them from moisture. No specific temperature storage requirements apply – store at normal room temperature. Check the expiry date (marked "EXP" on the carton and blister) before taking any tablet. The expiry date refers to the last day of that month.

Do not use Onglyza if the packaging is damaged or shows signs of tampering. Do not flush unused tablets down the toilet or throw them in household waste. Return any unused or expired medication to your pharmacy for safe disposal to help protect the environment from pharmaceutical contamination.

What Does Onglyza Contain?

Each Onglyza 2.5 mg tablet contains saxagliptin 2.5 mg (as hydrochloride). The tablets also contain lactose, microcrystalline cellulose, and other standard pharmaceutical excipients. The 2.5 mg tablets are pale yellow to light yellow, round, biconvex, with "2.5" printed on one side and "4214" on the other in blue ink.

Active Ingredient

The active substance is saxagliptin. Each 2.5 mg film-coated tablet contains 2.5 mg saxagliptin (as saxagliptin hydrochloride). Each 5 mg film-coated tablet contains 5 mg saxagliptin (as saxagliptin hydrochloride).

Inactive Ingredients (Excipients)

The other ingredients are:

• Tablet core: lactose monohydrate, microcrystalline cellulose (E460i), croscarmellose sodium (E468), magnesium stearate
• Film coating: polyvinyl alcohol, macrogol 3350, titanium dioxide (E171), talc (E553b), and yellow iron oxide (E172)
• Printing ink: shellac, indigo carmine (E132)

Lactose Content

Onglyza tablets contain lactose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Sodium Content

This medicine contains less than 1 mmol sodium (23 mg) per dose, meaning it is essentially "sodium-free." This is relevant for patients on a sodium-restricted diet.

Tablet Appearance and Packaging

2.5 mg tablets: Pale yellow to light yellow, biconvex, round film-coated tablets. Printed with "2.5" on one side and "4214" on the other side in blue ink.

5 mg tablets: Pink, biconvex, round film-coated tablets. Printed with "5" on one side and "4215" on the other side in blue ink.

Available in aluminium blister packs of 14, 28, or 98 tablets in non-perforated calendar blisters and 30×1 or 90×1 tablets in perforated unit-dose blisters. Not all pack sizes may be marketed in your country.

How Does Onglyza Work in the Body?

Saxagliptin inhibits the enzyme DPP-4, which normally degrades the incretin hormones GLP-1 and GIP. By extending the activity of these hormones, Onglyza enhances glucose-dependent insulin secretion and suppresses glucagon release after meals, thereby lowering blood sugar levels without causing hypoglycaemia when used as monotherapy.

After eating, the intestine releases two key incretin hormones: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones are responsible for what is known as the "incretin effect" – the observation that oral glucose produces a greater insulin response than the same amount of glucose given intravenously. In healthy individuals, GLP-1 and GIP account for approximately 50–70% of the total insulin response after a meal.

In patients with type 2 diabetes, the incretin effect is significantly impaired. While GLP-1 levels may be somewhat reduced, the more important problem is that the pancreatic beta cells become less responsive to GLP-1 signalling. Furthermore, the enzyme dipeptidyl peptidase-4 (DPP-4) rapidly degrades both GLP-1 and GIP, with a half-life of only 1–2 minutes in the bloodstream. This means that even the incretin hormones that are released are quickly inactivated.

Saxagliptin selectively and reversibly binds to the DPP-4 enzyme, blocking its ability to degrade GLP-1 and GIP. This results in 2–3 fold higher levels of active intact incretins circulating after a meal. The elevated GLP-1 levels then stimulate glucose-dependent insulin secretion from the pancreatic beta cells and suppress inappropriate glucagon secretion from the alpha cells. The crucial word here is "glucose-dependent" – when blood sugar is normal or low, the incretin-mediated insulin stimulation diminishes, which is why DPP-4 inhibitors carry a much lower risk of hypoglycaemia compared to sulphonylureas.

Pharmacokinetic Profile

After oral administration, saxagliptin is rapidly absorbed, reaching peak plasma concentrations within approximately 2 hours (4 hours for its active metabolite, 5-hydroxy saxagliptin). The metabolism of saxagliptin occurs primarily via the CYP3A4/5 enzyme system, producing the active metabolite which is approximately half as potent as saxagliptin at inhibiting DPP-4. The terminal half-life is 2.5 hours for saxagliptin and 3.1 hours for the active metabolite, but the clinical duration of DPP-4 inhibition extends to 24 hours, supporting once-daily dosing.

Approximately 75% of the administered dose is excreted by the kidneys (24% as unchanged saxagliptin, 36% as the active metabolite), with 22% eliminated via the faecal route. This significant renal excretion explains why dose reduction is necessary in patients with moderate to severe kidney impairment. Saxagliptin is not highly protein-bound (negligible binding), which reduces the potential for protein displacement drug interactions.

Frequently Asked Questions About Onglyza