• Soliqua is a combination insulin product that contains insulin glargine and lixisenatide that may be used to treat type 2 diabetes in adults.
• Soliqua works through the combined action of insulin glargine and lixisenatide. Insulin glargine is a biosynthetic human insulin analog of rDNA origin that has been made using genetic engineering technology. Although it resembles human insulin in most of its structure, the amino acid arginine in position A21 has been replaced by glycine and two arginines have been added to the C-terminus of the B-chain. The primary activity of insulin is to allow cells throughout the body to uptake glucose (sugar) and convert it into a form that can be used by these cells for energy.
• Lixisenatide mimics the actions of GLP-1, a naturally occurring hormone that helps to regulate blood glucose levels. By binding to and activating the GLP-1 receptor, it stimulates insulin secretion and lowers glucagon secretion when blood glucose levels are high. It also causes a slowing down in how fast the stomach empties.
• Soliqua belongs to the class of medicines known as antidiabetic combination agents. The ingredients in Soliqua are insulin glargine, which belongs to the class of medicines known as long-acting insulins, and lixisenatide, which belongs to the class of medicines known as glucagon-like peptide-1 (GLP-1) agonists; it may also be called an incretin mimetic.

• May be used alongside diet and exercise to control blood sugar levels in adults with type 2 diabetes who require long-acting insulin.
• Soliqua is an easy-to-use pen injector that is given subcutaneously (under the skin) once a day.
• Available as a fixed-dose combination of insulin glargine 100 units/mL and lixisenatide 33 mcg/mL (Soliqua 100/33). This is the only dose of Soliqua available so this may help eliminate some dosing errors.
• Ideal for people not meeting their A1C goals who are inadequately controlled on basal insulin (less than 60 units daily), lixisenatide, or oral medications for type 2 diabetes such as metformin.
• The insulin glargine contained in Soliqua forms microprecipitates when injected under the skin (subcutaneously), which allows the insulin to be released slowly from the injection site. Lasts for 24 to 36 hours and only needs to be given once a day.
• The pen delivers doses from 15 to 60 units in a single injection. The maximum dose is 60 units daily (this equates to 60 units of insulin glargine and 20mcg of lixisenatide).
• The recommended starting dose is 15 units/day for those on < 30 units of basal insulin daily or 30 units/day for those on 30-60 units of basal insulin/day. Increase dosage upwards or downwards by 2 to 4 units every week until good blood glucose control is reached.
• One Soliqua pen will last between 5 and 20 days depending on the dose.
• Weight gain is not a common side effect of Soliqua (insulin glargine and lixisenatide). An average weight loss of 0.1 and 0.3 kg (0.2 and 0.7 lb) has been reported. In contrast, patients using only insulin glargine had a weight gain of 1.1 and 2 kg (2.6 and 4.4 lb).
• One of the components of Soliqua, lixisenatide may pose a risk to the fetus in pregnant women; therefore, it should only be used in pregnancy if the benefits outweigh the risks. There is not enough data about the risks of taking lixisenatide during breastfeeding and so Soliqua should only be used if the benefits justify the risks. Insulin glargine does not pass into breast milk.
• At usual dosages, lixisenatide does not prolong the QTc interval to any relevant extent.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Low blood sugar levels (hypoglycemia) are the most common side effect of Soliqua. The risk of hypoglycemia increases with tighter blood sugar controls, changes in meal patterns, certain coadministered medications, and changes in physical activity levels. People with liver or kidney disease may be at a higher risk of hypoglycemia.
• Nausea, nasopharyngitis, diarrhea, upper respiratory tract infection, and headache are also commonly reported side effects.
• All insulins can cause potassium levels to go low (this is called hypokalemia). Insulin may also cause sodium retention, fluid retention, and swelling, itching, redness, or lumps around the injection site. There is a risk of infection if a Soliqua pen is shared.
• Not suitable for people with type 1 diabetes or who have a history of allergic reactions to any of the components of Soliqua. Allergic reactions, including anaphylaxis, have been observed more frequently in lixisenatide-treated patients than placebo-treated patients. Advise patients to seek urgent medical attention if these occur.
• May not be suitable for people with a history of pancreatitis or gastroparesis, in combination with prandial insulin, or in combination with any other product that contains a GLP-1 agonist.
• The dosage of Soliqua may need to be reduced for liver or kidney disease. Blood glucose levels should be carefully monitored in people with these conditions.
• Seniors may be more susceptible to the side effects of long-acting insulins, such as insulin glargine. The dosage of Soliqua in elderly people should be conservative. They may also have more difficulty using the pen due to poor vision or dexterity problems, making it difficult to dial the correct dosage or inject the insulin under their skin.
• Additional dosage titration may be needed to minimize the risk of hypoglycemia or hyperglycemia during times of physical activity, changes in meal patterns, renal or hepatic impairment, acute illness, or when used in conjunction with other medications.
• Frequent monitoring of blood glucose levels throughout the day is required in people requiring dosage changes in insulin or in those with concurrent illness
• Soliqua should not be administered intravenously, intramuscularly, or via an insulin pump.
• May not be suitable for people with visual impairment who rely on audible clicks to dial their dose.
• Interacts with several other medications and should not be used with similar types of insulin (brand names include Lantus, Toujeo, or Basaglar) or GLP-1 agonists such as semaglutide.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

• Administer one hour before your first meal of the day (ie, an hour before breakfast).
• Tell your doctor if you have ever had an allergic reaction to any type of insulin before you start using Soliqua.
• Soliqua only needs to be administered once a day, but try to inject it at the same time each day. Your doctor will tell you how much you need to use each day.
• Ensure your healthcare provider has shown you how to use Soliqua before attempting to self-administer it yourself.
• Always check the Soliqua 100/33 label before administration. There are many different types of insulin products and medication errors are common. Always check your pens inside the box to ensure they are Soliqua 100/33. The pens are colored light green with an orange injection button. Talk to your doctor or pharmacist if you are unsure.
• Visually inspect the pen for floating particles and discoloration before administration. Only use Soliqua if the solution is clear and colorless to almost colorless. Air bubbles are normal. Check the expiry date on the side of the pen and do not use it if it has expired.
• Soliqua is best administered subcutaneously (under the skin) into the front of your thighs or the lower part of your abdomen, avoiding the area around your belly button (stay an inch away from your belly button). If somebody else is giving you your injection they can also administer it into the outer area of your upper arm. Change your injection site each day so that you are not injecting into the same spot each time. Only inject into clear, healthy skin. Do not inject into any areas that are bruised, tender, red, scaly, or hard. You should also not inject scars, stretch marks, or areas of psoriasis.
• When you are ready to inject, take a new pen out of the refrigerator at least an hour before using it. Cold medicine is more painful to inject. Pull off the green cap. Wipe the rubber seal with an alcohol swab then attach a new needle. Always make sure you dial up the correct dose of Soliqua for you.
• Choose a place to inject and hold the pen at a 90-degree angle to the cleaned injection site (straight up and down). Push the needle into the skin. Place your thumb on the injection button then press in and hold. Keep holding until you see 0 in the dose window, then count to ten. Then remove the pen and needle from the skin, remove the needle, and throw it away in an FDA-approved sharps box.
• Your pen is intended to be used for more than one dose. While a pen is in use, you can leave it out of the refrigerator for up to 28 days. You just need to replace the needle each time you use it.
• Needles are not included in a box of Soliqua. Only use needles that are compatible for use with your Soliqua 100/33 prefilled pen. If you are not sure which needles to use, ask your doctor or pharmacist.
• The dosage of Soliqua needs to be individualized. This may take time, so ensure you monitor your blood sugars regularly when titrating the dosage of Soliqua, and tell your doctor the results.
• Never share your Soliqua with other people. Store your pens as recommended on the label.
• Inject your insulin exactly as directed by your doctor. Take all other medications as prescribed.
• Your insulin requirements may change if you become unwell, develop an infection, or have other medical conditions. Surgery, injury, mental stress, diet, and how much exercise you do can also affect how much insulin you need. Puberty, pregnancy, and menopause can also affect insulin requirements. Conditions that delay food absorption or stomach emptying can slow down the time it takes to break down and absorb food which can change how much insulin you need.
• Be alert for symptoms of hypoglycemia which may include a headache, sweating, trembling, anxiety, confusion, irritability, rapid breathing, or a fast heartbeat. People with hypoglycemia may also faint, and severe hypoglycemia that is left untreated may be fatal. Tell your family, friends, and caregivers to give you some fast-acting sugar (such as some jellybeans, fruit juice, or honey) if they notice you have symptoms of hypoglycemia, and then follow it up with a more substantial meal or glucagon injection if you are unconscious.
• Insulin is easily broken down by extreme temperatures, which means you need to be careful if you live in a part of the U.S. that gets very hot in summer, or very cold in winter.
• Store your unused Soliqua 100/33 pen in the refrigerator at 36°F to 46°F (2°C to 8°C). Protect the pen from light. Do not use past the expiration date. Do not freeze Soliqua 100/33 pens and do not use Soliqua 100/33 if it has been frozen. After your first use, you can store your Soliqua 100/33 pen at room temperature no higher than 77°F (25°C) for up to 28 days. After 28 days, throw it away, even if there is some medicine left in the pen.
• Replace the pen cap after each use to protect it from light. Do not store the Soliqua 100/33 pen with the needle attached. Keep your Soliqua 100/33 pens, pen needles, and all medicines out of the reach of children. When finished, dispose of the Soliqua pen in an FDA-approved sharps container. Do not throw away the Soliqua 100/33 pen in your household trash.
• If you are going out in the sun, always use an insulated bag protected by a cool pack to ensure your Soliqua doesn't heat up; but avoid freezing it. During cold weather, keep your Soliqua close to your skin so your body heat keeps it at a more even temperature. Discard any Soliqua that you think may have inadvertently got too hot or too cold. The expiry date on Soliqua applies to unopened, refrigerated insulin.

• Starts to lower blood glucose levels two hours after injection and keeps working for at least 24 hours.
• Soliqua was significantly more effective than insulin glargine or lixisenatide at improving HbA1c levels in two randomized studies conducted on people with type 2 diabetes. After 30 weeks of treatment, the mean change in HbA1c from baseline was -1.6 with Soliqua compared to -1.3 with insulin glargine and -0.9 with lixisenatide. 74% of Soliqua patients achieved an HbA1c of < 7% after 30 weeks compared to 59% of those assigned insulin glargine and 33% assigned lixisenatide. In those inadequately controlled with basal insulin, 55.1% achieved an HbA1c < 7% by week 30 compared to 29.6% assigned insulin glargine.
• Weight gain can occur with insulin-containing products, including Soliqua, and has been attributed to the tissue-building (anabolic) effects of insulin, as noted by the manufacturer. In contrast, glucagon-like peptide-1 (GLP-1) agonists typically lead to weight loss. The combined use of these 2 products may help to offset the weight gain that some patients experience with the use of insulin glargine (brand names: Basaglar, Lantus, Toujeo) alone. Research has shown that patients using insulin glargine/lixisenatide (Soliqua) had a weight loss of 0.3 kg (0.6 lbs), while patients who received only insulin glargine had a weight increase of 1.1 kg. Those using only lixisenatide had a weight loss of 2.3 kg.

Medicines that interact with Soliqua may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Soliqua. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Soliqua include:

• aloe vera
• antibiotics, such as doxycycline and minocycline
• antidepressants such as SSRIs (eg, fluoxetine, sertraline), or monoamine oxidase inhibitors (MAOI) such as selegiline, isocarboxazid, and phenelzine
• antiepileptics, such as fosphenytoin and phenytoin
• antipsychotics, such as aripiprazole, chlorpromazine
• antivirals such as amprenavir, atazanavir, and fosamprenavir
• aspirin
• beta-blockers, such as acebutolol, atenolol, or timolol
• diuretics, such as furosemide, chlorthalidone, or hydrochlorothiazide
• fluoroquinolone antibiotics, such as ciprofloxacin or norfloxacin
• gemfibrozil
• heart medications such as captopril, candesartan, or clonidine
• HIV medications such as ritonavir or saquinavir
• hormones, such as estradiol, estrone, and norethindrone
• lithium
• nalidixic acid
• niacin
• pentamidine
• potassium salts
• salmeterol
• steroids, such as cortisone, dexamethasone, fludrocortisone, or prednisone
• sucralfate
• tacrolimus or pimecrolimus
• turmeric
• warfarin
• other insulins
• other medications that affect blood sugar levels or are used for diabetes, such as chlorpropamide, glimepiride, or glipizide.

Lixisenatide slows gastric emptying which may affect the absorption of other medications. Some experts suggest administering medications at least one hour before Soliqua.

Alcohol may also interact with Soliqua by blocking the production of glucose by the liver, causing hypoglycemia.

Note that this list is not all-inclusive and includes only common medications that may interact with Soliqua. You should refer to the prescribing information for Soliqua for a complete list of interactions.