Soliqua and Xultophy: The Insulin Plus GLP-1 Combination Pens
Two once-daily pens combine basal insulin with a GLP-1 drug in a fixed ratio. Here is what is in each one, who their labels cover, how they are dosed, what they cost, and why they never became popular.
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Two products in the US combine basal insulin and a GLP-1 drug in a single pen. Both were approved on the same day in November 2016. Neither became a blockbuster, and most people who take a GLP-1 have never heard of either.
They are worth understanding anyway, for three reasons. If you have type 2 diabetes and use insulin, one of them may come up. If you have ever wondered what happened to lixisenatide, the answer is that it lives inside Soliqua. And they illustrate something about how the whole class has moved: these pens were designed for an era when GLP-1s were an add-on to insulin, and the field has largely gone the other direction.
This is not medical advice. Every dosing detail below is a summary of the FDA-approved prescribing information and the Instructions for Use packaged with each pen; the schedule that applies to any individual is the one on their own prescription. Insulin dosing in particular is set and adjusted by a prescriber.
Why combine insulin with a GLP-1 at all?
Basal insulin is very good at lowering fasting blood sugar and very reliable about two side effects: weight gain and low blood sugar.
GLP-1 receptor agonists push in the opposite direction on both. They reduce appetite and body weight, and because they only stimulate insulin release when blood sugar is high, they carry little hypoglycemia risk on their own.
Put them together and the theory is appealing. The insulin does the heavy glucose lowering; the GLP-1 blunts the weight gain and, by improving post-meal control, lets you get there with less insulin.
The practical argument was simpler still: one injection instead of two, one pen instead of two, one copay instead of two.
What is Soliqua 100/33?
Sanofi’s product, approved November 21, 2016. It was approved as NDA 208673 and, like all US insulin products, was deemed a biologics license application in March 2020 under the BPCI Act, so the FDA now lists it as BLA 208673. Each milliliter contains 100 units of insulin glargine and 33 mcg of lixisenatide [1]. In the research literature it is often called iGlarLixi.
The label describes injecting it subcutaneously once a day, within the hour before the first meal of the day. The pen delivers 15 to 60 units per injection. The maximum daily dosage is 60 units, which contains 60 units of insulin glargine and 20 mcg of lixisenatide [1].
Starting dosages in the label depend on where you are coming from: 15 units for people who are new to basal insulin, already on a GLP-1 receptor agonist, or on less than 30 units of basal insulin; and 30 units for people inadequately controlled on 30 to 60 units of basal insulin [1]. Basal insulin or a GLP-1 receptor agonist must be discontinued before starting.
Two Warnings and Precautions were added recently: severe gastrointestinal adverse reactions (section 5.8) in May 2025, and pulmonary aspiration during general anesthesia or deep sedation (section 5.13) in November 2024 [1]. The label also instructs patients not to administer Soliqua concurrently with another GLP-1 receptor agonist, and warns that more than 60 units a day would overdose the lixisenatide component [1]. The Medication Guide was revised in March 2026 [3].
Soliqua matters for one more reason. Sanofi announced in October 2022 that it was discontinuing standalone Adlyxin, and it left the US market on January 1, 2023 [4]. Soliqua is now the only US product containing lixisenatide.
What is Xultophy 100/3.6?
Novo Nordisk’s product, also approved November 21, 2016, and likewise transitioned from NDA 208583 to BLA 208583 in March 2020. Each milliliter contains 100 units of insulin degludec and 3.6 mg of liraglutide [2].
The label describes a starting dose of 10 units once daily for people new to basal insulin or a GLP-1 receptor agonist, or 16 units for people already on one. The maximum daily dosage is 50 units, which contains 50 units of insulin degludec and 1.8 mg of liraglutide — the same maximum liraglutide dose used in Victoza. As with Soliqua, liraglutide or basal insulin must be discontinued before starting [2].
Because liraglutide is in the mix, Xultophy carries the class boxed warning for risk of thyroid C-cell tumors [2]. Soliqua does not, because lixisenatide is an exendin-based peptide rather than a human GLP-1 analog.
How do they compare side by side?
| Soliqua 100/33 | Xultophy 100/3.6 | |
|---|---|---|
| Maker | Sanofi | Novo Nordisk |
| Insulin | Insulin glargine | Insulin degludec |
| GLP-1 | Lixisenatide (short-acting) | Liraglutide (long-acting) |
| Max daily dose | 60 units (60 units glargine + 20 mcg lixisenatide) | 50 units (50 units degludec + 1.8 mg liraglutide) |
| Timing | Within the hour before the first meal of the day | Once daily |
| Boxed warning | No thyroid C-cell warning | Thyroid C-cell tumors |
| Acquisition cost | $57.09 per mL, about $171 per 3 mL pen | $85.90 per mL, about $258 per 3 mL pen |
| FDA listing runs to | December 31, 2027 | December 31, 2026 |
Costs are National Average Drug Acquisition Cost values effective August 19, 2026 — what pharmacies pay on average, not what patients pay [5]. Listing dates are the listing certification expiry dates in the FDA National Drug Code directory, checked September 14, 2026 [9]. They reflect routine annual certification, not a discontinuation announcement: neither Sanofi nor Novo Nordisk has announced that either pen is being withdrawn, and both products’ Novo Nordisk and Sanofi materials were still being updated in late 2025 and 2026.
The most meaningful clinical difference is the GLP-1 component. Lixisenatide is short-acting and works mainly on after-meal glucose spikes, which is why Soliqua’s label ties dosing to the first meal of the day. Liraglutide is long-acting and works across the day, which is why Xultophy has no meal timing instruction.
What does the evidence show?
The LixiLan program supported Soliqua. LixiLan-O studied patients uncontrolled on oral agents, LixiLan-L studied patients uncontrolled on insulin, and LixiLan-G asked a question directly relevant to this article: what happens if you switch someone off a GLP-1 receptor agonist onto the combination pen?
In LixiLan-G, A1C fell from 7.8 percent at baseline to 6.7 percent with iGlarLixi, versus 7.4 percent for people who stayed on their GLP-1 [6]. That is a real improvement, and it is roughly what you would expect from adding insulin.
One finding is worth knowing about, and it comes straight from the Soliqua label rather than a review: in the Soliqua trials, anti-lixisenatide antibodies developed in approximately 43 percent of patients and anti-insulin-glargine antibodies in 21.0 to 26.2 percent. In the wider pool of nine placebo-controlled lixisenatide studies, 70 percent of exposed patients tested positive for anti-lixisenatide antibodies, and in the 2.4 percent with the highest antibody concentrations the glycemic response was attenuated [1]. Antibody formation is common with peptide drugs and does not automatically mean a drug stops working, but it is a real difference from the human GLP-1 analogs.
On the heart, the picture is mixed and the honest answer is that neither combination has its own cardiovascular outcomes trial. Lixisenatide’s standalone trial, ELIXA, enrolled 6,068 patients with type 2 diabetes and a recent acute coronary syndrome and found a hazard ratio of 1.02 (95 percent CI 0.89 to 1.17) — safe, but no benefit [7]. Liraglutide’s LEADER trial did show a benefit, with a hazard ratio of 0.87 for major cardiovascular events and 0.78 for cardiovascular death [8], but it studied standalone liraglutide, not the fixed-ratio pen.
Why did these never take off?
Four reasons, and they compound.
They are diabetes drugs in a weight-loss moment. Neither is approved for chronic weight management, and neither can be. The public conversation about GLP-1s since 2021 has been almost entirely about weight.
The fixed ratio cuts both ways. Convenience comes at the cost of flexibility. If someone needs more insulin but not more GLP-1, or vice versa, a fixed ratio cannot deliver it. As insulin needs rise, the GLP-1 dose rises with them until the cap is reached.
The GLP-1 components are the weakest in the class. Lixisenatide never showed a cardiovascular benefit and its standalone brand is gone. Liraglutide lost decisively to semaglutide in head-to-head trials on both A1C and weight. A combination built around the strongest available GLP-1 would look different, and no such product exists in the US.
The whole treatment sequence flipped. These pens were designed for a world in which people went to insulin first and added a GLP-1 later. Current practice increasingly puts a GLP-1 in earlier, sometimes well before insulin. A product built to rescue insulin users is aimed at a shrinking group.
What should you take from this?
If you have type 2 diabetes and use basal insulin, these pens are a legitimate option that your prescriber may raise, and the convenience argument is not trivial. One injection is genuinely easier to sustain than two.
If you are asking about them because you want a GLP-1 for weight, these are not the products — and a pen that contains insulin is not a small thing to take on.
Some questions worth bringing to an appointment: Which GLP-1 am I actually getting, and how does it compare to the standalone options? What happens if I need more insulin than the cap allows? What does my plan cover? And if I am already on a GLP-1, what happens when I stop it to start this?
That last one matters, because both labels require discontinuing the prior GLP-1 receptor agonist or basal insulin before the combination pen is started — Soliqua’s section 2.2 says so for every starting-dose scenario [1], and Xultophy’s label carries the same requirement [2]. The labels describe a clean stop and start rather than a taper or an overlap; they do not describe an interval, which is why the timing is something a prescriber sets in advance.
Sources
- SOLIQUA 100/33 (insulin glargine and lixisenatide injection) — US prescribing information, US Food and Drug Administration
- XULTOPHY 100/3.6 (insulin degludec and liraglutide injection) — US prescribing information, US Food and Drug Administration
- Soliqua 100/33 Medication Guide, Sanofi
- Diabetes treatment Adlyxin will no longer be available in the US, MPR, 2022
- NADAC (National Average Drug Acquisition Cost), Centers for Medicare & Medicaid Services
- Clinical review of the LixiLan program and iGlarLixi, Advances in Therapy, 2019
- Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome (ELIXA), New England Journal of Medicine, 2015
- Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (LEADER), New England Journal of Medicine, 2016
- National Drug Code Directory, US Food and Drug Administration, openFDA (listing certification expiry checked September 14, 2026)
Questions people ask
What is in Soliqua 100/33?
Insulin glargine at 100 units per mL and lixisenatide at 33 mcg per mL, in a single once-daily pen from Sanofi. Lixisenatide is a short-acting GLP-1 receptor agonist. Soliqua is the only product still sold in the US that contains lixisenatide, since Sanofi withdrew the standalone Adlyxin brand at the start of 2023.
What is in Xultophy 100/3.6?
Insulin degludec at 100 units per mL and liraglutide at 3.6 mg per mL, in a once-daily pen from Novo Nordisk. Liraglutide is the same molecule as Victoza and Saxenda. Because of the liraglutide component, Xultophy carries the class boxed warning for thyroid C-cell tumors.
Are these weight loss drugs?
No. Both are approved only for improving blood sugar in adults with type 2 diabetes. Neither label covers chronic weight management. The GLP-1 component is there partly to offset the weight gain that basal insulin usually causes, not to produce weight loss on its own.
Can you take Soliqua or Xultophy with Ozempic or Trulicity?
No. Both labels require that any basal insulin or GLP-1 receptor agonist be discontinued before starting. Combining two GLP-1 receptor agonists is not recommended in any setting.
Is Xultophy being discontinued?
Novo Nordisk has not announced a discontinuation, but the product's FDA listing certification runs only to December 31, 2026 as of September 2026, and it is a small, niche product. Soliqua's listing runs to December 31, 2027. Listing expiration is a routine annual renewal, not an announcement, so this is a status to check rather than a conclusion.
Why would a doctor choose a combination pen over two separate injections?
One injection instead of two, one pen instead of two, and one copay instead of two. The tradeoff is that you cannot adjust the insulin and the GLP-1 independently, because the ratio is fixed. Whether that tradeoff works for a given person is a clinical judgment.
What does Soliqua cost?
Its National Average Drug Acquisition Cost was $57.09 per milliliter effective August 19, 2026, which is about $171 for a 3 mL pen at pharmacy acquisition cost. Xultophy was $85.90 per milliliter, about $258 per pen. How long a pen lasts depends entirely on your insulin dose, so there is no meaningful monthly figure.
Does the GLP-1 in these pens protect the heart?
Not lixisenatide. Its cardiovascular outcomes trial, ELIXA, found it safe but showed no cardiovascular benefit, with a hazard ratio of 1.02. Liraglutide, the GLP-1 in Xultophy, did show a benefit in its own LEADER trial, but that trial studied standalone liraglutide at doses up to 1.8 mg, not the fixed-ratio combination.
This article summarizes FDA labeling, published research and company information current as of September 14, 2026. It is not medical advice and does not replace a conversation with your own healthcare provider. How we research and verify.