Soliqua vs Xultophy: How the Two Insulin + GLP-1 Pens Compare

Soliqua and Xultophy are fixed-ratio insulin + GLP-1 combination pens, and the difference comes down to which insulin and which GLP-1 drug each one pairs. Soliqua 100/33 is insulin glargine plus lixisenatide ^[1]. Xultophy 100/3.6 is insulin degludec plus liraglutide ^[2]. Both are injected under the skin, both list Initial U.S. Approval: 2016, and both are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus ^[1][2]. Neither pen is indicated for weight management — the labels list type 2 diabetes glycemic control only ^[1][2]. In research papers, the insulin glargine + lixisenatide fixed-ratio combination is abbreviated iGlarLixi ^[6].

The biggest practical differences are the dosing caps, the timing rules, and one safety distinction: Xultophy carries a boxed warning about thyroid C-cell tumors tied to its liraglutide component, while the Soliqua label highlights reviewed here show no boxed warning section ^[1][2]. One more note on sources: the Xultophy labeling excerpt used here was revised 06/2022 and carries a notice that it may not be the latest FDA-approved version, so details should be checked against current labeling ^[2].

What does each pen actually contain?

Soliqua 100/33 contains 100 units insulin glargine and 33 mcg lixisenatide per mL, supplied in a 3 mL single-patient-use pen ^[1]. Insulin glargine is an insulin analog and lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist ^[1].

Xultophy 100/3.6 contains 100 units/mL of insulin degludec and 3.6 mg/mL of liraglutide, also in a 3 mL single-patient-use pen ^[2]. Insulin degludec is a long-acting human insulin analog and liraglutide is a GLP-1 receptor agonist ^[2]. Each Xultophy dosage unit contains 1 unit of insulin degludec and 0.036 mg of liraglutide ^[2].

How do the dosing rules differ?

	Soliqua 100/33	Xultophy 100/3.6
Insulin component	Insulin glargine [1]	Insulin degludec [2]
GLP-1 component	Lixisenatide [1]	Liraglutide [2]
Timing	Once a day, within the hour before the first meal [1]	Once a day at the same time each day, with or without food [2]
Pen dose range	15–60 units per injection [1]	10–50 units per injection [2]
Maximum daily dose	60 units (60 units insulin glargine + 20 mcg lixisenatide) [1]	50 units (50 units insulin degludec + 1.8 mg liraglutide) [2]
Starting dose, new to basal insulin or GLP-1 RA	15 units once daily [1]	10 units (10 units degludec + 0.36 mg liraglutide) [2]
Starting dose, already on therapy	15 units once daily also applies to patients currently on less than 30 units of basal insulin or on a GLP-1 RA; 30 units once daily if inadequately controlled on 30–60 units basal insulin [1]	16 units (16 units degludec + 0.58 mg liraglutide) if currently on basal insulin or a GLP-1 RA [2]

Those starting doses are label figures for defined patient groups, not suggestions for any individual. Both labels direct readers to the full prescribing information for titration recommendations (Soliqua section 2.3; Xultophy section 2.3) ^[1][2].

Both pens share the same core administration rules: inject under the skin in the abdomen, thigh, or upper arm ^[1][2]. On site rotation, the labels are worded differently. Soliqua’s label says to rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis ^[1]. Xultophy’s label says to rotate injection sites to reduce the risk of lipodystrophy and localized cutaneous amyloidosis ^[2]. Neither pen may be given intravenously or by infusion pump, and neither may be diluted or mixed with other insulin products or solutions ^[1][2].

Do you have to stop your current insulin or GLP-1 first?

Yes, per both labels. Soliqua says to discontinue basal insulin or a GLP-1 receptor agonist prior to initiation (section 2.2) ^[1]. Xultophy says to discontinue therapy with liraglutide or basal insulin prior to initiation (section 2.2) ^[2].

For a missed Soliqua dose, the Medication Guide says to take the next scheduled dose at the regular time and not to take an extra dose or increase the dose to make up for it ^[3].

Why does Xultophy have a boxed warning and Soliqua does not?

Xultophy’s boxed warning states that liraglutide, one of its components, causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Xultophy causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, because the human relevance of the rodent findings has not been determined ^[2].

Because of that warning, Xultophy is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) ^[2]. The label also states that routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Xultophy ^[2].

The Soliqua label highlights reviewed here contain no boxed warning section ^[1]. Soliqua’s contraindications are episodes of hypoglycemia and serious hypersensitivity to insulin glargine, lixisenatide, or any excipient ^[1]. Xultophy shares those two contraindications in addition to the thyroid-cancer history ones ^[2].

What warnings do both pens share?

The two labels overlap heavily on safety:

• Never share a pen between patients, even if the needle is changed ^[1][2].
• Overdose risk from medication errors: each pen contains two drugs, patients are told to check the label before each injection, not to exceed the maximum dose, and not to use other GLP-1 receptor agonists alongside it ^[1][2].
• Hypoglycemia may be life-threatening; monitoring should increase with changes in dosage, coadministered glucose-lowering drugs, meal pattern, or physical activity, and in patients with renal or hepatic impairment or hypoglycemia unawareness ^[1][2].
• Hypokalemia may be life-threatening; potassium should be monitored in at-risk patients ^[1][2].
• Acute gallbladder disease: gallbladder studies are indicated if cholelithiasis or cholecystitis is suspected ^[1][2].
• Fluid retention and heart failure when used with PPAR-gamma agonists (TZDs): observe for heart failure and consider dosage reduction or discontinuation if it occurs ^[1][2].
• Anaphylaxis and severe, life-threatening generalized hypersensitivity reactions can occur with either pen ^[1][2].

On the kidneys, the labels differ in wording. Soliqua warns of acute kidney injury due to volume depletion and states it is not recommended in patients with end-stage renal disease ^[1]. Xultophy’s label says acute kidney injury has been reported postmarketing for liraglutide, usually with nausea, vomiting, diarrhea, or dehydration, sometimes requiring hemodialysis ^[2].

On the pancreas, Soliqua’s label notes acute pancreatitis has been observed with GLP-1 receptor agonists, and its Medication Guide names pancreatitis as the most important information a patient should know ^[1][3]. Xultophy’s label reports postmarketing fatal and non-fatal hemorrhagic or necrotizing pancreatitis for liraglutide and says to discontinue promptly if pancreatitis is suspected ^[2].

What changed recently on the Soliqua label?

Two Soliqua warnings are recent additions. Severe Gastrointestinal Adverse Reactions (section 5.8) was added 5/2025; the label says Soliqua is not recommended in patients with severe gastroparesis ^[1]. Pulmonary Aspiration During General Anesthesia or Deep Sedation (section 5.13) was added 11/2024 ^[1]. Patients are told to inform all healthcare providers that they use Soliqua before any surgery or procedure involving general anesthesia or deep sedation, because GLP-1 receptor agonists have been linked to food or liquid entering the lungs during such procedures ^[1][3].

For comparison, the Xultophy label excerpt used here was revised 06/2022, with Warnings and Precautions section 5.9 listed as the recent major change, and the PDF carries a notice that it may not be the latest FDA-approved version ^[2].

What side effects do people actually report?

The most common adverse reactions reported in at least 5% of patients treated with Soliqua are hypoglycemia, nausea, nasopharyngitis, diarrhea, upper respiratory tract infection, and headache ^[1]. For Xultophy, the list is nasopharyngitis, headache, nausea, diarrhea, increased lipase, and upper respiratory tract infection ^[2].

Both labels include an Immunogenicity section (6.2). Soliqua’s label states that patients may develop antibodies to insulin glargine and lixisenatide, and that alternative antidiabetic therapy should be considered if glycemic control worsens or fails, or if significant injection-site or allergic reactions occur ^[1].

Does Soliqua affect other medications?

Lixisenatide delays gastric emptying, which can affect how oral medications are absorbed. The label says oral contraceptives, antibiotics, and acetaminophen should be taken at least 1 hour before a Soliqua injection or 11 hours after ^[1][3]. The Medication Guide adds that Soliqua may lower the amount of medicine in the blood from oral birth control pills, making them less effective at preventing pregnancy ^[3].

Both labels also warn that antiadrenergic drugs — beta-blockers, clonidine, guanethidine, and reserpine — may blunt or reduce the signs and symptoms of hypoglycemia ^[1][2].

How should a Soliqua pen be stored?

Unused Soliqua pens stay refrigerated at 36–46°F (2–8°C) and protected from light ^[3]. After first use, the pen is stored at room temperature no higher than 77°F (25°C) and used for up to 28 days, then discarded even if medicine remains ^[3]. Do not freeze the pen, and do not store it with the needle attached ^[3].

Where does neither pen belong?

Each label lists limitations of use. Soliqua is not recommended in combination with any other product containing a GLP-1 receptor agonist, and is not recommended for treating diabetic ketoacidosis ^[1]. Xultophy is not recommended as first-line therapy for patients inadequately controlled on diet and exercise, is not for type 1 diabetes or diabetic ketoacidosis, and is not recommended with any other liraglutide-containing product or another GLP-1 receptor agonist ^[2].

It is not known whether Soliqua is safe and effective in children ^[3]. Both labels say use in pregnancy only if the potential benefit justifies the potential risk to the fetus (section 8.1) ^[1][2].

What cardiovascular evidence sits behind each GLP-1 component?

Neither pen has its own cardiovascular outcomes trial in the materials reviewed here. Xultophy’s label section 14.4 covers cardiovascular outcomes trials conducted with liraglutide 1.8 mg and insulin degludec — that is, the separate components, not the fixed combination ^[2].

For lixisenatide, the ELIXA trial enrolled 6,068 patients with type 2 diabetes who had a myocardial infarction or hospitalization for unstable angina within the previous 180 days, with a median follow-up of 25 months ^[7]. The primary composite endpoint (cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina) occurred in 406 patients (13.4%) on lixisenatide versus 399 (13.2%) on placebo — a hazard ratio of 1.02 (95% CI 0.89–1.17), meeting noninferiority (P<0.001) but not superiority (P=0.81) ^[7]. Hospitalization for heart failure showed a hazard ratio of 0.96 (95% CI 0.75–1.23) and death a hazard ratio of 0.94 (95% CI 0.78–1.13) ^[7]. Lixisenatide was not associated with higher rates of serious adverse events, severe hypoglycemia, pancreatitis, pancreatic neoplasms, or allergic reactions than placebo; the trial was funded by Sanofi (NCT01147250) ^[7]. These are component data, not evidence for the Soliqua combination itself.

What happened to standalone lixisenatide (Adlyxin)?

Adlyxin, the standalone lixisenatide injection, is no longer available in the United States, according to Sanofi ^[4]. A posting on the FDA’s Drug Shortages tracker indicated the product was discontinued, as reported in February 2023 ^[4]. Adlyxin had FDA approval in 2016 as an adjunct to diet and exercise for glycemic control in adults with type 2 diabetes ^[4]. Same-class alternatives listed at the time included Bydureon BCise, Byetta, Ozempic, Rybelsus, Trulicity, and Victoza ^[4]. Only standalone Adlyxin is sourced as discontinued — nothing in these materials says either combination pen is being withdrawn ^[4].

What about cost, and what should you ask a prescriber?

No patient price or list price for either pen appears in the materials reviewed here. The closest public benchmark is CMS’s National Average Drug Acquisition Cost (NADAC), weekly reference data searchable by NDC description — but NADAC reflects what pharmacies pay on average to acquire drugs, not a patient price or list price ^[5].

Dose changes should happen only on a prescriber’s instruction, and the prescriber should demonstrate pen technique before first use ^[3]. Because both labels require stopping the prior basal insulin or GLP-1 receptor agonist before starting the combination pen, the timing of that switch is a prescriber decision ^[1][2].

To report suspected adverse reactions: for Soliqua, contact sanofi-aventis at 1-800-633-1610 or FDA at 1-800-FDA-1088 ^[1]; for Xultophy, contact Novo Nordisk Inc. at 1-800-727-6500 or FDA at 1-800-FDA-1088 ^[2].

Sources

1. US Food and Drug Administration. SOLIQUA 100/33 (insulin glargine and lixisenatide) injection, for subcutaneous use. Prescribing information.
2. US Food and Drug Administration. XULTOPHY 100/3.6 (insulin degludec and liraglutide) injection, for subcutaneous use. Prescribing information.
3. Sanofi. SOLIQUA 100/33 (insulin glargine and lixisenatide) injection. Medication Guide.
4. Drug Topics. Diabetes Treatment Adlyxin Will No Longer Be Available in the US.
5. Medicaid.gov. NADAC (National Average Drug Acquisition Cost) 2026. Updated September 8, 2026.
6. Advances in Therapy. Combining GLP-1 Receptor Agonists and Basal Insulin in Older Adults with Type 2 Diabetes: Focus on Lixisenatide and Insulin Glargine. October 23, 2019.
7. PubMed. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome.
8. PubMed. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.
9. openFDA. Drug NDC directory API. Last updated September 11, 2026.