Komboglyze (saxagliptin, metformin)

How does Komboglyze work?

• Komboglyze tablets contain two active ingredients, metformin and saxagliptin.
• Metformin is a type of antidiabetic medicine known as a biguanide. It works in a number of ways to decrease the amount of sugar in the blood. Firstly, it reduces the amount of sugar produced by cells in the liver. Secondly, it increases the sensitivity of muscle cells to insulin. This enables these cells to remove sugar from the blood more effectively. Finally, it also delays absorption of sugar from the intestines into the bloodstream after eating.
• Saxagliptin is a type of antidiabetic medicine known as a dipeptidyl peptidase-4 (DPP-4) inhibitor. It helps to reduce blood sugar levels by preventing the breakdown of two incretin hormones, called glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). These hormones are normally produced naturally by the body in response to food intake. They stimulate the pancreas to produce insulin in response to increasing levels of glucose in the blood, and they also reduce the production of glucagon, which is a hormone that normally increases glucose production by the liver. These actions help control blood sugar levels.
• This combination of medicines helps control blood sugar levels both directly after meals and between meals.

How do I take Komboglyze?

• One Komboglyze tablet should be taken twice a day, morning and evening.
• The tablets should be taken with a meal.
• If you forget to take a dose of Komboglyze, take it with your next meal, unless you were due to take a tablet then anyway. In this case just take the dose you are due to take as usual and leave out the forgotten tablet. Do not take a double dose to make up for a missed tablet.

What should I know before taking Komboglyze?

• It is important that you continue to follow the diet and exercise advice given to you by your doctor or nurse while you are taking Komboglyze. This medicine only helps to control your blood sugar levels and should not be used as a substitute for eating healthily and taking regular exercise.
• Hypoglycaemia (low blood glucose) has been commonly reported when Komboglyze is used in combination with sulphonylurea medicines, eg gliclazide or glibenclamide, or with insulin. Symptoms of hypoglycaemia usually occur suddenly and may include cold sweats, cool pale skin, tremor, anxious feeling, unusual tiredness or weakness, confusion, difficulty in concentration, excessive hunger, temporary vision changes, headache, nausea and palpitations. You should talk to your doctor or diabetes specialist about this and make sure you know what to do if you experience these symptoms.

Who shouldn't take Komboglyze?

• People with type 1 diabetes.
• People with diabetic keto-acidosis (due to severe and inadequately treated diabetes).
• People with moderate to severely decreased kidney function.
• People with liver problems.
• People with acute heart failure or who have recently had a heart attack.
• People with conditions that cause breathing to be ineffective, ie to not effectively oxygenate the blood or remove carbon dioxide from the lungs (respiratory failure).
• People with reduced blood flow to vital internal organs (shock).
• People with severe infections or blood poisoning (sepsis).
• People who are dehydrated.
• People who drink large amounts of alcohol or who suffer from alcoholism.
• Women who are pregnant or breastfeeding.
• People who are allergic to any ingredient of the medicine.
• People who have had a serious allergic reaction to another DPP4 inhibitor, eg sitagliptin, vildagliptin.
• Komboglyze is not recommended for children and adolescents under 18 years of age, because its safety and effectiveness have not been established in this age group.

Komboglyze should be used with caution in

• People over 75 years of age.
• People with an underactive immune system, either due to a disease or a treatment.

Can I take Komboglyze while pregnant or breastfeeding?

• The safety of saxagliptin for use during pregnancy has not been established. It should not be used during pregnancy. Diabetes mellitus is usually controlled using insulin during pregnancy, because this provides a more stable control of blood sugar. Metformin many also sometimes be used. However, as Komboglyze contains a combination of metformin and saxagliptin it should not be used during pregnancy.
• If you get pregnant while taking Komboglyze, or want to plan a pregnancy, you should seek medical advice from your doctor.
• It is not known if saxagliptin passes into breast milk. Metformin does pass into breast milk. The manufacturer states that Komoboglyze should not be used by breastfeeding mothers. Seek further medical advice from your doctor.

What are the possible side effects of Komboglyze?

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with Komboglyze. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

Very common 

• Low blood sugar levels (hypoglycaemia - when used with a sulphonylurea or insulin).

Common 

• Upper respiratory tract infection.
• Urinary tract infection.
• Gastroenteritis.
• Sinusitis.
• Inflammation of the nose and throat, causing a blocked or runny nose and sore throat.
• Metallic taste.
• Headache.
• Feeling or being sick.
• Dizziness.
• Muscle pain.
• Indigestion.
• Fatigue.

If you want any more information about the possible side effects of Komboglyze you should talk to your doctor or pharmacist, or read the leaflet that comes with the medicine.

Can I take other medicines with Komboglyze?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with Komboglyze. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to make sure that the combination is safe.

The following medicines may reduce the blood level of saxagliptin and so could make it less effective at controlling blood sugar:

• carbamazepine
• dexamethasone
• phenobarbital
• phenytoin
• rifampicin.

There may be an increased risk of developing lactic acidosis if you take medicines that can affect your kidney function with metformin. These include the following:

• diuretic medicines such as furosemide
• non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen. It's best to check with your doctor before taking this type of painkiller with Komboglyze.

If you are prescribed any of the following medicines with Komboglyze you may be more likely to get low blood sugar (hypoglycaemia), so your doctor may want you to monitor your blood sugar levels more frequently if you start treatment with one of these:

• ACE inhibitors such as captopril
• disopyramide
• MAOI antidepressants, such as phenelzine, tranylcypromine or isocarboxazid
• other antidiabetic medicines, such as sulphonylureas (eg gliclazide, glibenclamide) or insulin.

Medicines that increase blood sugar levels as a side effect may make Komboglyze less effective at controlling blood sugar. Medicines that can increase blood sugar levels include the following:

• antipsychotic medicines, such as chlorpromazine, olanzapine, risperidone
• beta-2-agonists, such as salbutamol, salmeterol
• corticosteroids, such as prednisolone
• glucosamine
• oestrogens and progestogens, such as those found in oral contraceptives or HRT
• diuretics, such as bendroflumethiazide or furosemide.

Your doctor may want to monitor your blood sugar if you start or stop treatment with any of these while taking Komboglyze.

Octreotide and lanreotide may also affect blood sugar levels. If you are being treated with one of these medicines your doctor may want to check your blood sugar levels and adjust your metformin dose if necessary.

The following medicines may increase the blood level of metformin, which could increase the risk of its side effects. Your doctor may need to reduce your metformin dose if you regularly take one of these:

• cimetidine
• dolutegravir
• rilpivirine
• telaprevir
• topiramate
• vandetanib.

A drop in the number of blood cells called platelets in the blood has been seen in some people taking the antihistamine ketotifen in combination with metformin. The manufacturer of ketotifen recommends that it should be avoided in people taking metformin.

References:

https://www.ema.europa.eu/en/documents/product-information/komboglyze-epar-product-information_en.pdf

https://www.netdoctor.co.uk/medicines/diabetic/a8903/komboglyze-saxagliptin-metformin/

https://www.medicines.org.uk/emc/product/7608/pil

https://www.drugs.com/uk/komboglyze.html

https://chealth.canoe.com/drug/getdrug/komboglyze

https://www.ema.europa.eu/en/medicines/human/EPAR/komboglyze