Awiqli (insulin icodec-abae) is a once-weekly long-acting insulin that was approved by the US Food and Drug Administration (FDA) in 2026 for adults with type 2 diabetes. The medication is designed to be taken only once each week using the Awiqli FlexTouch pen, which may help people who have trouble sticking to daily basal injections.
In clinical trials involving more than 2,600 participants, the once-weekly injection lowered hemoglobin A1c (HbA1c) levels and controlled fasting blood sugar as well as daily basal insulin.
While Awiqli reduces injection frequency, it is still an insulin product and therefore shares many of the risks and side effects seen with daily basal insulins. Understanding these potential effects will help you spot early warning signs so you can work with your healthcare provider to manage them effectively.
1. Hypoglycemia (low blood sugar)
Low blood sugar is the most common side effect of Awiqli and other basal insulins. Insulin helps cells absorb glucose from the bloodstream. Taking too much insulin, skipping meals, exercising more than usual, or drinking alcohol can cause blood sugar to fall. Medication errors, such as mixing up the Awiqli pen with another injectable product or using a syringe to withdraw insulin from the pen, can also lead to overdosing.
According to the prescribing information, severe hypoglycemia is defined as an event that causes significant cognitive impairment requiring help from another person. In clinical trials, up to 12% of insulin-naïve participants experienced at least one episode of severe or clinically significant low blood sugar.
Early symptoms of hypoglycemia include:
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- dizziness
- sweating
- shaking
- fast heartbeat
- hunger
- headache
- mood changes
If blood sugar drops further, confusion, blurred vision, slurred speech, and loss of consciousness may occur. Because Awiqli has a long half-life, increases in blood sugar after treatment for hypoglycemia may be delayed, so repeated monitoring is important.
What to do:
Carry glucose tablets or another high-sugar snack so you can treat low blood sugar immediately. Eat or drink fast-acting carbohydrates, rest, and check your blood sugar again after 15 minutes. If you become unconscious, people around you should turn you on your side and seek emergency medical care.
Severe episodes may require a hormone called glucagon, which a trained person can administer. Discuss hypoglycemia management with your healthcare provider, especially if you frequently experience low blood sugar, drink alcohol, or are physically active.
2. Serious allergic reactions
Allergic reactions occur when your immune system treats the insulin or one of the pen’s ingredients as a foreign substance. Insulin icodec is similar to human insulin but is produced by yeast cells and stabilized with additives. Approximately 0.4% of patients treated with Awiqli developed hypersensitivity reactions during clinical trials.
Severe, life-threatening generalized allergies may also occur, including:
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- anaphylaxis
- angioedema (swelling of deeper layers of skin)
- bronchospasm (tightening of airways)
- low blood pressure
- shock
Symptoms of a severe reaction include a rash over your entire body, trouble breathing, and a fast heartbeat accompanied by sweating.
What to do:
Stop using Awiqli and seek emergency medical care if you develop a widespread rash, swelling of the face or tongue, difficulty breathing, or severe dizziness. Because anaphylaxis can progress quickly, carrying antihistamines will not be enough. This is a medical emergency. People with a history of severe allergies to insulin or any of Awiqli’s ingredients should not take this medication.
3. Hypokalemia (low potassium)
Insulin can cause potassium to move into cells, reducing the amount circulating in the bloodstream. Awiqli may lead to hypokalemia, which can be life-threatening. Low potassium increases the risk of heart rhythm problems, muscle weakness, and paralysis.
Symptoms of hypokalemia include:
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- weakness
- muscle cramps
- tingling
- abnormal heartbeats
- paralysis or respiratory failure, in severe cases
Because hypokalemia often develops gradually, routine blood tests may reveal low potassium before symptoms appear.
Your risk increases if you’re also experiencing diarrhea or vomiting, or taking diuretic medications and other glucose-lowering drugs, which can further lower potassium levels. People with kidney problems may be at higher risk because the kidneys help regulate potassium.
What to do:
Speak to your doctor about potassium monitoring if you are on diuretics, have kidney disease, or notice muscle weakness. Do not take potassium supplements without medical advice, as too much potassium can also be dangerous.
4. Heart failure when used with thiazolidinediones
Thiazolidinediones (TZDs) are oral medications used for type 2 diabetes. When taken together with insulin, TZDs can cause fluid retention and heart failure. Cases of cardiac failure have been reported when pioglitazone (Actos), a TZD, is used with insulin.
Symptoms include:
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- shortness of breath
- sudden weight gain
- swelling of the ankles or feet
- unusual tiredness
- a feeling of tightness in the chest
Because heart failure can develop gradually, weigh yourself regularly and note any rapid changes.
What to do:
If you take TZDs such as pioglitazone, talk to your doctor before starting Awiqli. In many cases, the TZD dose may need to be reduced or discontinued. Report any new or worsening heart symptoms immediately. If you already have heart failure or significant heart disease, your healthcare provider may suggest an alternative to Awiqli.
5. Injection-site reactions
Awiqli is injected under the skin of the thigh, upper arm, or abdomen, and injection-site reactions are common with all injectable medications. These reactions occurred in about 1.8% of Awiqli-treated patients in clinical trials. The most frequent signs were redness (erythema) and itching (pruritus), and most reactions were mild.
Injection-site reactions can also include:
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- bruising
- pain
- injection-site hypersensitivity
- swelling
- hives (urticaria)
- injection-site mass
When insulin is injected into the skin, the body may react to the needle or the solution by releasing inflammatory chemicals. Injecting repeatedly into the same area increases the risk of irritation, lumps, or scar tissue. Using improper technique, injecting into irritated skin, or injecting cold insulin straight from the refrigerator can also trigger reactions.
What to do:
Rotate injection sites within the same body area to reduce the risk of lipodystrophy and localized cutaneous amyloidosis or deposits of protein in the skin. Avoid injecting into areas that are tender, bruised, scarred, or have pits or lumps. Let the insulin come to room temperature before injecting.
If you experience persistent redness, swelling, or pain at the injection site, contact your healthcare provider. Severe injection-site reactions accompanied by hives or difficulty breathing may indicate an allergy and require medical care.
6. Lipodystrophy (skin thickening or thinning)
Repeated injections at the same site can cause lipodystrophy, which is a change in the fat tissue under the skin. This includes lipohypertrophy (thickening) and lipoatrophy (thinning). Although lipodystrophy was reported in very few Awiqli-treated patients during trials, it remains a potential complication.
Lipodystrophy can create visible lumps or dents at injection sites and may reduce the absorption of insulin, leading to unpredictable blood sugar control. Localized cutaneous amyloidosis, which is the formation of hard, lumpy deposits of protein, has also been reported with repeated injections. Both conditions may make it harder to control diabetes and may be cosmetically bothersome.
What to do:
Rotate injection sites with every dose. Do not inject into lumps, thickened areas, or scars. Inspect injection sites regularly for changes in texture or appearance and report any concerns to your doctor. If lipodystrophy develops, your healthcare provider may suggest using an alternative site or adjusting the injection technique.
7. Weight gain
Weight gain can occur with any insulin therapy. In Awiqli clinical trials, patients treated for 26-52 weeks gained an average of 1.4 to 2.8 kg (3-6 lb).
Improved blood sugar control reduces the loss of glucose in the urine and decreases dehydration, so some weight gain is expected. Insulin also has anabolic effects, meaning it encourages the body to store energy as fat and reduces the breakdown of fat tissue. Overeating to avoid hypoglycemia or using excess insulin may also contribute to weight gain.
What to do:
Focus on balanced meals, appropriate portion sizes, and regular physical activity. Work with a dietitian or diabetes educator to create a meal plan that matches your insulin dose and keeps blood sugar stable without excessive calorie intake.
Discuss any sudden or unexplained weight gain with your doctor, especially if accompanied by swelling or shortness of breath, which could signal fluid retention or heart issues.
8. Peripheral edema (swelling of hands or feet)
Peripheral edema refers to swelling, typically in the ankles, feet, or hands, due to fluid retention. Insulin can cause the kidneys to retain sodium and water, leading to swelling. The risk increases when insulin is combined with medications that also cause water retention, such as TZDs. Heart or kidney problems can make the body more prone to edema.
In the clinical trials, peripheral edema occurred in 1.2% of patients with type 2 diabetes treated with Awiqli.
What to do:
Contact your doctor if you notice persistent swelling, rapid weight gain, or difficulty breathing. Reducing salt intake, elevating your legs, and engaging in regular physical activity may help with mild edema.
Do not start or stop diuretics (water pills) without medical advice. If edema is related to TZD use, the medication may need to be discontinued.
9. Vision changes and retinopathy
Rapid improvement in blood sugar control can sometimes lead to temporary vision changes, a worsening of diabetic retinopathy, or acute peripheral neuropathy. Intensification or rapid improvement in glucose control has been associated with transitory, reversible changes in eye refraction and worsening of diabetic retinopathy. Long-term glycemic control, however, decreases the risk of eye and nerve complications.
Long-standing high blood sugar can damage the small blood vessels in the eyes. When blood sugar levels drop quickly, it can cause fluid shifts in the lens of the eye, leading to blurry vision. Existing retinopathy may worsen temporarily as the eye adjusts to improved glucose levels.
What to do:
If you experience sudden changes in vision or new floaters after starting Awiqli, contact your eye doctor. Regular eye exams are essential for everyone with diabetes, particularly when changing insulin regimens. Gradual titration of insulin and close monitoring of blood sugar may reduce the risk of vision changes.
In the long run, maintaining good blood sugar control helps protect your eyes.
Who should use caution?
Although Awiqli is indicated for adults with type 2 diabetes, some groups should exercise caution. People with liver or kidney problems, heart failure, or other heart conditions, or who take thiazolidinediones, need close monitoring.
Individuals who drink alcohol may have unpredictable blood sugar and require more frequent testing. Those with impaired vision should not use the pen without assistance to avoid dosing errors.
Because Awiqli is not approved for children or adolescents, its safety and effectiveness in younger populations are unknown.
Bottom line
Awiqli is the first FDA-approved once-weekly basal insulin for adults with type 2 diabetes. Reducing injection frequency can make insulin therapy more manageable and may improve adherence for people who struggle with daily shots.
Like other insulins, the most common side effects of Awiqli are low blood sugar, allergic reactions, injection-site problems, weight gain, and swelling. Some side effects, such as heart failure when combined with pioglitazone, require caution.
Before switching to Awiqli, discuss your medical history, current medications, and lifestyle with your healthcare provider. Ask about strategies to manage hypoglycemia, how to adjust your weekly dosing, and whether your current medications might interact with Awiqli. With careful planning and monitoring, you may find that once-weekly insulin offers a convenient option for controlling your diabetes while maintaining safety.
Frequently Asked Questions
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Sources
PR Newswire. (2026). FDA approves Novo Nordisk’s Awiqli®, the first and only once-weekly basal insulin treatment for adults with type 2 diabetes. https://www.prnewswire.com/news-releases/fda-approves-novo-nordisks-awiqli-the-first-and-only-once-weekly-basal-insulin-treatment-for-adults-with-type-2-diabetes-302726839.html
HIGHLIGHTS OF PRESCRIBING INFORMATION OF AWIQLI. https://www.novo-pi.com/awiqli.pdf
Once-weekly Long-acting Insulin | Awiqli® (insulin icodec) injection 700 U/mL. (n.d.). https://www.awiqli.com/
