Soliqua 100/33 and Xultophy 100/3.6, insulin-GLP-1 combination pens, reach US market

Two once-daily pens that combine a long-acting insulin with a GLP-1 receptor agonist entered the US market on the same day, Nov. 21, 2016: Sanofi's Soliqua 100/33 and Novo Nordisk's Xultophy 100/3.6. FDA drug listing records show a marketing start date of Nov. 21, 2016 for Soliqua 100/33, made by Sanofi-Aventis U.S. LLC, and its prescribing information lists initial US approval in 2016 ^[1][2].

The two products are fixed-ratio combinations: one injection delivers both an insulin and a GLP-1 drug in a set proportion. Soliqua 100/33 contains insulin glargine and lixisenatide at 100 units of insulin glargine and 33 micrograms of lixisenatide per milliliter in a 3 mL single-patient-use pen ^[2]. Insulin glargine is a long-acting basal insulin; lixisenatide is a GLP-1 receptor agonist ^[1][2]. Xultophy 100/3.6 combines insulin degludec and liraglutide. Its pen strengths, dosing and labeling details have not been disclosed in the records reviewed here.

Soliqua is indicated, along with diet and exercise, to improve blood sugar control in adults with type 2 diabetes ^[2]. It is not for type 1 diabetes, and it is not recommended for treating diabetic ketoacidosis ^[2]. The label also states it has not been studied with mealtime (prandial) insulin ^[2].

How it is used and what it requires

The Soliqua pen delivers 15 to 60 units in a single injection, given under the skin once a day within the hour before the first meal of the day. The maximum daily dose is 60 units, which contains 60 units of insulin glargine and 20 micrograms of lixisenatide ^[2].

Starting doses differ by history. For patients who have not used basal insulin or a GLP-1 drug, who are currently on a GLP-1 drug, or who take less than 30 units of basal insulin daily, the starting dose is 15 units once daily. For patients already taking 30 to 60 units of basal insulin daily, the starting dose is 30 units once daily ^[2].

In both cases, the label directs that basal insulin or a GLP-1 receptor agonist be discontinued before Soliqua is started, and it does not recommend using Soliqua with any other product containing a GLP-1 receptor agonist ^[2]. That means patients cannot simply add the combination pen on top of an existing GLP-1 injection or their current basal insulin ^[2]. Changes to an insulin regimen should be made under close medical supervision with more frequent blood sugar monitoring ^[2].

The most common side effects reported in 5% or more of patients in trials were low blood sugar (hypoglycemia), nausea, nasopharyngitis, diarrhea, upper respiratory tract infection and headache ^[2]. The label carries warnings for serious allergic reactions, acute pancreatitis, life-threatening low blood sugar, acute kidney injury from volume depletion, severe gastrointestinal reactions, low potassium, gallbladder disease and pulmonary aspiration during general anesthesia or deep sedation ^[2]. Soliqua is not recommended in patients with severe gastroparesis or end-stage renal disease ^[2]. Lixisenatide slows stomach emptying, so oral contraceptives, antibiotics and acetaminophen should be taken at least one hour before or 11 hours after the injection ^[2].

Why it matters for patients

The arrival of these products created a category that did not exist before: a single daily pen containing both a basal insulin and a GLP-1 drug. For someone already taking two separate daily injections, that means one device instead of two, with the two ingredients locked in a fixed ratio rather than adjusted independently.

The trade-off is flexibility. Because the ratio is fixed, a patient cannot raise the GLP-1 portion without also raising the insulin portion, and the maximum daily dose caps the lixisenatide at 20 micrograms ^[2]. Anyone currently on semaglutide (Ozempic, Wegovy, Rybelsus), dulaglutide, tirzepatide (Mounjaro, Zepbound) or another GLP-1 would need to stop that medicine before starting, since combining GLP-1 drugs is not recommended ^[2]. These are not GLP-1 medicines used for weight loss; they are type 2 diabetes treatments, and their GLP-1 components are lixisenatide and liraglutide rather than semaglutide or tirzepatide.

Cost and coverage have not been disclosed here.

What happens next

The Soliqua label has been revised since launch. The current prescribing information lists a May 2025 update to the severe gastrointestinal adverse reactions warning and a November 2024 update on pulmonary aspiration during general anesthesia or deep sedation ^[2]. Novo Nordisk's Xultophy 100/3.6 was part of the same Nov. 21, 2016 market entry, but its current labeling, dosing and availability have not been reported in the records reviewed here.