Tresiba (insulin degludec) is an ultra-long-acting basal insulin, and its most common side effects are hypoglycemia, weight gain, and injection site reactions. Because Tresiba has a half-life exceeding 25 hours, longer than most basal insulins, its effects linger in the body. That long duration is actually an advantage for steady blood sugar control, but it also means that if a side effect like low blood sugar occurs, the insulin driving it doesn’t clear quickly.
Hypoglycemia
Low blood sugar is the most frequent side effect of Tresiba, as it is with all insulin therapy. Symptoms include shakiness, sweating, a fast heartbeat, dizziness, confusion, and hunger. In clinical trials, confirmed hypoglycemic episodes occurred at similar rates whether patients used Tresiba or other basal insulins, but one consistent finding stood out: Tresiba caused fewer episodes of nocturnal hypoglycemia (low blood sugar while sleeping) compared to insulin glargine. This held true across both type 1 and type 2 diabetes trials.
Nocturnal lows are particularly concerning because you can’t recognize the warning signs while asleep, so this difference matters in daily life. If you’re switching to Tresiba from another basal insulin, your doctor will likely adjust your dose carefully during the transition period, since the long duration of action means dose changes take a couple of days to fully take effect.
Weight Gain
Weight gain is a well-documented effect of insulin therapy in general, and Tresiba is no exception. Insulin is an anabolic hormone, meaning it promotes the storage of energy as fat and muscle tissue. In the clinical trial program, the average weight gain after 52 weeks was about 1.8 kg (roughly 4 pounds) for people with type 1 diabetes and about 3.0 kg (roughly 6.5 pounds) for people with type 2 diabetes.
Those are averages, and individual variation is wide. Some trials showed more modest changes of 1.3 kg at 26 weeks, while one study of people with type 2 diabetes on a basal-bolus regimen recorded a mean gain of 4.0 kg by 78 weeks. Patients already using a basal insulin before switching to Tresiba tended to gain less, sometimes under 1 kg. The amount of weight change depends heavily on your overall insulin dose, diet, and activity level.
Injection Site Reactions
Redness, swelling, itching, or mild pain at the injection site can occur. These reactions are usually mild and tend to fade within a few days as your body adjusts. Rotating your injection sites (abdomen, thighs, upper arms) helps reduce irritation.
A longer-term concern with any insulin you inject repeatedly is lipodystrophy, where the fat tissue under the skin either thickens into small lumps (lipohypertrophy) or thins out (lipoatrophy). These changes aren’t just cosmetic. Injecting into a thickened area can make insulin absorption unpredictable, which makes blood sugar harder to control. Consistent site rotation is the best way to prevent this.
Allergic Reactions
Serious allergic reactions to Tresiba are rare but possible. Localized reactions at the injection site are the mildest form. In uncommon cases, the reaction can become systemic, producing widespread hives, swelling of the face or throat (angioedema), difficulty breathing, or a rapid drop in blood pressure. These are signs of anaphylaxis and require emergency treatment. If you’ve ever had a severe allergic reaction to insulin degludec or any of the inactive ingredients in Tresiba, you should not use it.
Potassium Drops
All insulins, including Tresiba, push potassium from the bloodstream into cells. This is a normal part of how insulin works, but in some people it can lower blood potassium to a level that causes problems, a condition called hypokalemia. Symptoms can include muscle weakness, cramping, fatigue, or an irregular heartbeat. The risk is higher if you’re also taking medications that lower potassium, such as certain diuretics. Your doctor may monitor your potassium levels periodically, especially early in treatment or if you’re on other medications that affect electrolyte balance.
Cardiovascular Safety
The large DEVOTE trial, which specifically tested whether Tresiba was safe for the heart, found that the risk of major cardiovascular events (heart attack, stroke, or death from cardiovascular causes) was similar between Tresiba and insulin glargine. All-cause mortality was also comparable between the two insulins. These findings held across age groups up to 74 years. In short, Tresiba does not appear to increase cardiovascular risk compared to other basal insulins.
Side Effects in Children
Tresiba is approved for pediatric use, and the side effect profile in children and adolescents looks similar to what’s seen in adults. In a clinical trial comparing Tresiba to insulin detemir in younger patients, the overall rate of adverse events was nearly identical between the two treatments (about 83% of participants in each group reported at least one event over the study period, mostly hypoglycemia-related). Rates of confirmed hypoglycemia, including nocturnal episodes, did not significantly differ between the two insulins in this age group. There was no clustering of hypoglycemic episodes in any specific age bracket, suggesting the safety profile is consistent across pediatric ages.
How Its Long Duration Affects Side Effects
Tresiba works differently from other basal insulins at the molecular level. After injection, it forms long chains of molecules under the skin that slowly break apart and release insulin into the bloodstream over more than 24 hours. This creates a very flat, steady insulin level with less peak-and-trough fluctuation than older basal insulins.
In practical terms, this means two things for side effects. First, the steady release is why nocturnal hypoglycemia rates are lower: there’s no pronounced spike of insulin activity at an inconvenient hour. Second, the long half-life means you have more flexibility in when you take your daily dose. If your injection time shifts by several hours from one day to the next, it has relatively little impact on your blood sugar stability. That said, if you do develop hypoglycemia from too high a dose, the insulin stays active longer, so recovery can take more time compared to shorter-acting basal insulins. Dose adjustments should be made gradually, typically waiting at least three to four days between changes to see the full effect.