Xultophy is a once-daily injection that combines two diabetes medicines in one pen: insulin degludec, a long-acting basal insulin, and liraglutide, a GLP-1 receptor agonist. It is approved for adults with type 2 diabetes who are not adequately controlled on basal insulin alone or on liraglutide alone. In the DUAL trial program Xultophy lowered A1C by roughly 1.5 to 2 percentage points and was generally weight neutral or led to modest weight loss compared with the weight gain typical of basal insulin alone.
What Xultophy Is
Xultophy is a fixed-ratio combination of insulin degludec (brand name Tresiba) and liraglutide (brand name Victoza), packaged in a single multi-dose pen. The strength is labeled 100 units per milliliter of insulin degludec and 3.6 milligrams per milliliter of liraglutide. The pen delivers in “dose steps” — 1 dose step equals 1 unit of insulin degludec plus 0.036 mg of liraglutide. The pen allows 1 to 50 dose steps per injection, equating to up to 50 units of degludec and 1.8 mg of liraglutide per day.
Insulin degludec is an ultra-long-acting basal insulin with a half-life over 24 hours, allowing flat, peakless coverage and flexible timing. Liraglutide is a GLP-1 receptor agonist that increases glucose-dependent insulin secretion, slows gastric emptying, suppresses glucagon, and reduces appetite. Combining them addresses both fasting glucose (insulin) and postprandial glucose plus weight effects (GLP-1).
Who Xultophy Is For
- Adults with type 2 diabetes inadequately controlled on basal insulin (less than 50 units/day) or on liraglutide
- People who need basal insulin but want to limit weight gain
- People on a GLP-1 receptor agonist who need additional fasting glucose control
- People who prefer one daily injection rather than two separate ones
Xultophy is not approved for type 1 diabetes, diabetic ketoacidosis, or as a standalone weight-loss medication. Read more about treatment pathways on our treatment overview.
Xultophy at a Glance
| Feature | Detail |
|---|---|
| Generic ingredients | Insulin degludec + liraglutide |
| Brand | Xultophy 100/3.6 (Novo Nordisk) |
| Drug class | Basal insulin + GLP-1 receptor agonist |
| Indication | Type 2 diabetes (adults) |
| Route | Subcutaneous injection |
| Frequency | Once daily, same time each day |
| Starting dose | 16 dose steps if switching from basal insulin or liraglutide |
| Maximum dose | 50 dose steps per day |
| Titration | 2 dose steps every 3 to 4 days based on fasting glucose |
| A1C reduction | Roughly 1.5 to 2.0 percentage points |
| Weight effect | Neutral or modest loss; less gain than insulin alone |
| Hypoglycemia risk | Moderate (insulin component) |
Benefits and Clinical Evidence
The DUAL clinical trial program studied Xultophy versus comparators across multiple populations:
- DUAL I — Xultophy vs. degludec alone vs. liraglutide alone in insulin-naive patients. A1C dropped 1.9% on Xultophy vs. 1.4% on degludec and 1.3% on liraglutide.
- DUAL II — Xultophy vs. degludec alone in patients on basal insulin. A1C 1.9% reduction vs. 0.9%, with weight loss favoring Xultophy.
- DUAL V — Xultophy vs. up-titrated insulin glargine in patients uncontrolled on basal insulin. A1C 1.8% reduction vs. 1.1%, less weight gain, and fewer hypoglycemic events.
- DUAL VII — Xultophy vs. basal-bolus insulin (glargine plus aspart). Similar A1C reductions but with significantly less hypoglycemia and weight gain on Xultophy.
Across the program Xultophy consistently produced A1C reductions of 1.5 to 2.0 percentage points, with weight neutrality or modest loss and a hypoglycemia rate lower than aggressive basal-bolus regimens.
How to Use Xultophy
- Inject once daily at any time, ideally the same time each day. If you miss a dose by less than 12 hours, take it as soon as you remember; if more, skip it and resume the next day.
- Rotate injection sites among the abdomen, front of thigh, or upper arm. Move at least 1 inch from the prior site.
- Allow the pen to reach room temperature for 15 to 30 minutes before injecting to reduce sting.
- Attach a new needle each time. Do not reuse needles.
- Start at 16 dose steps if switching from basal insulin or liraglutide, then titrate 2 steps every 3 to 4 days targeting a fasting plasma glucose of 72 to 90 mg/dL (or as your clinician sets).
- Do not exceed 50 dose steps in a 24-hour period.
- Store unused pens refrigerated; once in use, keep at room temperature and discard after 21 days.
Side Effects
Side effects combine both components:
- Hypoglycemia — the most common insulin-related side effect; higher risk if combined with sulfonylureas or with skipped meals.
- Nausea — from the liraglutide portion; usually mild and improves over weeks.
- Diarrhea, vomiting, decreased appetite — also GLP-1 related; often transient.
- Injection site reactions — redness, itching, mild swelling; typically resolve in days.
- Upper respiratory tract infections, headache — reported in trials.
- Lipohypertrophy — fatty lumps from repeat injection in the same spot; prevented by rotation.
Serious but Rare Risks
- Pancreatitis — discontinue if persistent severe abdominal pain develops
- Gallbladder disease — cholelithiasis and cholecystitis reported with GLP-1 agonists
- Thyroid C-cell tumors — boxed warning based on rodent data; contraindicated with personal/family history of medullary thyroid carcinoma or MEN 2
- Severe hypoglycemia — particularly with concurrent sulfonylurea or after exercise without dose adjustment
- Acute kidney injury — risk increases with dehydration from GI side effects
- Hypersensitivity reactions including anaphylaxis
Drug Interactions
- Sulfonylureas (glipizide, glyburide) — increased hypoglycemia risk; reduce sulfonylurea dose
- Other insulins — should not be co-administered
- Oral medications — delayed gastric emptying from liraglutide can slow absorption of certain drugs
- Drugs causing hyperglycemia (corticosteroids, atypical antipsychotics) — may require Xultophy dose increase
Cost and Coverage
Xultophy list price is roughly $900 to $1,100 for a typical 30-day supply, although Novo Nordisk savings cards can lower commercial copays substantially. Medicare and Medicaid coverage varies by formulary. The combination may be cost-comparable to taking degludec and liraglutide separately because both components are branded. Generic alternatives do not exist for either active ingredient.
How Xultophy Compares
| Therapy | A1C drop | Weight | Hypoglycemia |
|---|---|---|---|
| Xultophy | 1.5–2.0% | Neutral / modest loss | Moderate |
| Basal insulin alone | 1.0–1.5% | +2 to +4 kg | Moderate to high |
| Liraglutide alone | 1.0–1.5% | −2 to −3 kg | Low |
| Basal-bolus insulin | 1.5–2.0% | +3 to +5 kg | High |
| Soliqua (glargine + lixisenatide) | 1.5–1.8% | Neutral | Moderate |
Lifestyle Pairing
Medications work best alongside diet, activity, and weight management. Read about diet strategies for blood sugar control and A1C targets.
The Bottom Line
Xultophy combines insulin degludec and liraglutide into one daily injection for adults with type 2 diabetes uncontrolled on basal insulin or liraglutide alone. It delivers strong A1C reduction (1.5 to 2 percentage points), modest weight benefit relative to insulin monotherapy, and lower hypoglycemia than basal-bolus regimens. Side effects combine GI symptoms from the GLP-1 component and hypoglycemia from the insulin component. Cost is high without insurance coverage. Talk to your doctor about whether Xultophy fits your goals — particularly if you are gaining weight on insulin alone or need additional fasting glucose control on top of a GLP-1.
