What to Know About Insulin Degludec Side Effects

Every medication comes with potential side effects, and Insulin Degludec (brand name Tresiba) is no exception. The good news is that most people tolerate this ultra-long-acting basal insulin well. But it's important to know what's normal, what's not, and when you should call your doctor.

This guide covers the common and serious side effects of Insulin Degludec based on FDA labeling, plus practical tips for managing them.

What Is Insulin Degludec?

Insulin Degludec is an ultra-long-acting basal insulin made by Novo Nordisk. It's FDA-approved for type 1 diabetes (adults and children age 1+) and type 2 diabetes (adults). It works by forming a depot under the skin that slowly releases insulin over 42+ hours, giving you a flat, stable glucose-lowering effect with less day-to-day variability than many other basal insulins.

For more details on how it works, see our guide on Insulin Degludec's mechanism of action.

Common Side Effects

These side effects are reported frequently in clinical trials and are usually mild to moderate:

• Hypoglycemia (low blood sugar) — The most common side effect of any insulin. Symptoms include shakiness, sweating, fast heartbeat, dizziness, hunger, and confusion. Mild episodes can be treated with fast-acting glucose (juice, glucose tablets).
• Injection site reactions — Redness, swelling, or itching at the injection site. These usually go away within a few days. Rotating injection sites helps prevent them.
• Weight gain — Insulin therapy often leads to modest weight gain as your body uses glucose more efficiently.
• Peripheral edema — Mild swelling in your hands or feet, especially when starting insulin therapy.
• Lipodystrophy — Thickening or pitting of the skin at injection sites over time. Rotating sites is key to prevention.
• Upper respiratory tract infections — Cold-like symptoms reported in clinical trials.
• Headache — Usually mild and temporary.
• Nasopharyngitis — Sore throat and runny nose, similar to a mild cold.

Serious Side Effects

These are less common but require immediate medical attention:

• Severe hypoglycemia — Blood sugar drops low enough to cause seizures, loss of consciousness, or death. This is a medical emergency. People around you should know how to use glucagon. Call 911 if you can't treat it yourself.
• Hypokalemia (low potassium) — Insulin drives potassium into cells. Severely low potassium can cause muscle weakness, cramps, and dangerous heart rhythm changes. Your doctor may monitor potassium levels.
• Severe allergic reactions — Rare, but anaphylaxis can occur. Signs include whole-body rash, trouble breathing, rapid heartbeat, and swelling of the face or throat. Call 911 immediately.
• Heart failure risk with thiazolidinediones — If you take Pioglitazone (Actos) or Rosiglitazone (Avandia) along with Insulin Degludec, the combination can cause fluid retention and increase the risk of heart failure. Watch for rapid weight gain, shortness of breath, and swelling.

Side Effects in Specific Populations

Children

Insulin Degludec is approved for children age 1 and older with type 1 diabetes. Side effects are similar to adults, with hypoglycemia being the primary concern. Children may have difficulty recognizing or communicating low blood sugar symptoms, so parents and caregivers should monitor closely.

Older Adults

No dose adjustment is needed for older adults, but they may be more vulnerable to hypoglycemia and its consequences (falls, confusion). Careful glucose monitoring is recommended.

Pregnancy and Breastfeeding

There's limited data on Insulin Degludec in pregnancy. Your doctor will weigh the benefits and risks. Insulin is a natural hormone, and exogenous insulin is unlikely to harm a breastfed infant, but discuss it with your provider.

Kidney or Liver Problems

No dose adjustment is required, but insulin clearance may be reduced in people with kidney or liver impairment. Your doctor may ask you to monitor blood sugar more frequently.

How to Manage Side Effects

Managing Hypoglycemia

• Always carry fast-acting glucose (juice box, glucose tablets, candy)
• Check blood sugar regularly, especially when adjusting doses
• Don't skip meals
• Make sure family and coworkers know the signs of low blood sugar and how to help
• Consider wearing a medical alert bracelet

Managing Injection Site Reactions

• Rotate injection sites between your thigh, upper arm, and abdomen
• Don't inject into the same exact spot repeatedly
• Let the insulin reach room temperature before injecting (cold insulin stings more)

Managing Weight Gain

• Work with your doctor or a dietitian on a meal plan
• Regular physical activity helps with blood sugar control and weight management
• Don't reduce your insulin dose to avoid weight gain — this is dangerous

When to Call Your Doctor

Contact your healthcare provider if you experience:

• Frequent or severe low blood sugar episodes
• Signs of an allergic reaction (rash, swelling, difficulty breathing)
• Rapid unexplained weight gain or swelling (could indicate fluid retention)
• Persistent injection site problems that don't improve with rotation
• Any new or worsening symptoms after starting Insulin Degludec

Final Thoughts

Most people do well on Insulin Degludec (Tresiba), and its ultra-long duration means more stable blood sugar with fewer spikes and crashes compared to some other basal insulins. Side effects are generally manageable, and the most important one to watch for — hypoglycemia — can be minimized with proper dosing and monitoring.

If you're having trouble finding Tresiba in stock, Medfinder can help you locate pharmacies near you that have it available. And if cost is a concern, check out our guide to saving money on Insulin Degludec.