Dr. Ahmed Xultophy Vs Soliqua is a comparison of two injectable diabetes medicines. Both these injections are administered daily subcutaneously, just like insulin.
These are combo medicines and are used along with other diabetes medicines such as metformin, SGLT2 Inhibitors, Insulin, and Sulfonylureas such as Glipizide, Glimepiride, and Glyburide.
Both Xultophy and Soliqua contain two medicines in a fixed dose: basal insulin and a GLP-1 analog. However, they are different as they have different basal insulin and GLP-1 as given in the table below:
Drug | Basal Insulin | GLP-1 analog |
| Xultophy | Degludec | Liraglutide |
| Soliqua | Glargine | Lixisenatide |
Why Do You Need Xultophy or Soliqua?
Xultophy and Soliqua are two injectable fixed-dose combinations of basal insulin and a GLP-1 analog. Basal insulin is the usual preferred injectable medicine when oral medicines fail to achieve the target blood glucose.
Although very effective in controlling blood glucose, insulin use is associated with weight gain and an increased risk of hypoglycemia.
To counteract weight gain and reduce the risk of hypoglycemia associated with insulin, Xultophy and Soliqua have been marketed by NOVO and Sanofi Pharmaceuticals.
People who can benefit the most from Xultophy and Soliqua include the following:
- Those who have not achieved their glycemic goals despite maximum oral antidiabetic medications.
- People who are using basal insulin but have not achieved their glycemic targets or have weight gain and hypoglycemia.
- People who are scared of multiple injections or are too busy to get more than one injection daily.
Both Soliqua and Xultophy offer the advantage of once-daily dosing and provide a basal cover of insulin along with an injectable GLP-1 to prevent post-meal glycemic excursions.
How do Xultophy and Soliqua control your blood glucose without extra weight gain and hypoglycemia?
Xultophy and Soliqua are both a combination of a basal insulin and a GLP-1 analog. Although the risk is minimal, like all insulin, Insulin Degludec and Insulin Glargine can also result in hypoglycemia.
Similarly, there is an increased risk of weight gain with insulins, including basal insulins.
To counter these two common side effects of insulin, Xultophy, a combo of Liraglutide and Degludec, and Soliqua, a combo of Lixisenatide and Glargine, have been formulated.
Both Liraglutide and Lixisenatide lower blood glucose by enhancing insulin release in a glucose-dependent mechanism.
In addition, Liraglutide and Lixisenatide cause a delay in gastric emptying and make a person feel full, and suppress cravings and hunger.
The FDA has approved Liraglutide for weight loss under the brand name Saxenda. The weight loss effect of Liraglutide counters the weight gain effects of Insulin degludec.
Likewise, the weight-gaining effects of insulin glargine are countered to some extent by Lixisenatide.
Xultophy Vs Soliqua: Dosage and Frequency of Administration:
Insulin glargine and Degludec doses can be adjusted up to one unit when used alone. However, Liraglutide is usually titrated in increments of 0.6 mg dose (0.6, 1.2, 1.8 mg, etc), and Lixisenatide (Adlyxin) is administered in a dose of 10 mcg subQ for 14 days followed by 20 mcg per day.
When used in a fixed-dose combination as combo (Xultophy and Soliqua), the doses of both these GLP-1 analogs can be titrated in very small doses.
Xultophy Dose:
Xultophy injection is available as a pen that contains 100 units of Insulin Degludec and 3.6 mg of Liraglutide. That is why it is written as Xultophy 100/3.6.
The usual starting dose is 16 units. These units correspond to the Insulin Degludec dose. 16 units of Xultophy contains 16 units of Insulin degludec and 0.58 units of Liraglutide.
When the dose is increased from 16 to 17, that is one unit of Xultophy, this corresponds to only one unit of Injection Degludec and 0.036 units of Liraglutide. This dose titration is almost 16 times lower for Liraglutide when compared with Injection Victoza (Liraglutide).
Thus, Xultophy allows for smaller dose titration which can indirectly result in better tolerability and fine glucose control without risking side effects, especially hypoglycemia.
Soliqua Dose:
Soliqua injection is available as a pen that contains Insulin Glargine 100 units and an Injection of Lixisenatide 33 units. Hence, it is written as Soliqua 100/33.
Lixisenatide (Adlyxin), when administered as monotherapy, is administered in a starting dose of 10 mcg and then titrated up after 14 days to 20 mcg.
When administered as Soliqua, Lixisenatide is titrated in very small doses of 0.33 units which is 30 times lower than Adlyxin (Lixisenatide) dose titration.
Thus, a lower dose titration allows better tolerability and very fine glucose control with minimal side effects.
Here is a table summarizing the dose of Injection Xultophy Vs Sloiqua:
Dose | Xultophy | Soliqua |
| Dosage form | 100/3.6 per pen (100 units insulin Degludec and 3.6 units Liraglutide) | 100/33 per pen (100 units of insulin Glargine and 33 units of Lixisenatide) |
| Starting Dose | 16 units | 15 units |
| Maximum Daily Dose | 50 units (equivalent to 50 units of Insulin Degludec and 1.8 mg Liraglutide) | 60 units (equivalent to 60 units of Insulin Glargine and 20 mcg of Lixisenatide) |
| Dose titration | One unit increase is equivalent to one unit of Insulin Degludec and 0.036 units of Liraglutide | One unit increase is equivalent to one unit of Insulin Glargine and 0.33 units of Lixisenatide |
How effective is Xultophy Vs Soliqua in controlling blood glucose?
Because Xultophy and Soliqua are fixed-dose combinations of insulin and GLP-1 analog, they are more effective than either drug used alone.
Xultophy is supposedly more effective than Insulin degludec and Liraglutide when used in equivalent doses.
Similarly, Soliqua is more effective than Insulin Glargine (Lantus) and Adlyxin (Lixisenatide) when used alone.
The average A1C reduction observed in clinical trials with Insulin Degludec, Insulin Glargine, Liraglutide, Lixisenatide, Xultophy, and Soliqua are summarized in the table below:
Medications | A1C reduction |
| Insulin Degludec (Tresiba) | -0.36 to -1.67% |
| Liraglutide (Victoza) | -1.2% to -1.5% |
| Xultophy [Ref] | -1.31% (Vs -0.36% with Liraglutide)-1.94% (Vs -1.05% with Insulin Degludec)-1.67% (Vs -1.16% with Insulin Glargine) |
| Insulin Glargine (Lantus) | -0.9 to -1.72% |
| Lixisenatide (Adlyxin) | -0.8% |
| Soliqua [Ref] | -1.1% (Vs -0.6% with Insulin Glargine) |
From the table above, it is obvious that Xultophy is more effective in lowering A1C when compared to Liraglutide, Insulin Degludec, and Insulin Glargine.
Likewise, Soliqua is more effective than Insulin Glargine.
In the Bright study which included patients with impaired renal function, Insulin Glargine performed better than Injection Degludec in terms of A1C reduction (-1.64% Vs -1.59%). However, in the subgroup of patients who had a GFR of more than 90 ml/minute, Insulin Degludec performed better [Ref].
How effective are Xultophy Vs Soliqu when used for weight management?
Insulin causes weight gain while GLP-1 analogs cause weight loss. Since Xultophy and Soliqua are combos of both Insulin and GLP-1, they do not cause significant weight gain or weight loss.
The weight gain/ weight loss effects of each drug are summarized in the table below:
Medications | Weight Gain/ Weight Loss |
| Insulin Degludec (Tresiba) | ⇑ 2.2 – 6.6 lbs (1 to 3 kg) weight gain |
| Liraglutide (Victoza) | ⇓ 6.6 – 13.2 lbs (3 – 6 kg) weight loss |
| Xultophy | ⇑ 4.4 lbs (2 kg) weight gain |
| Insulin Glargine (Lantus) | ⇑ 1.5 to 8.1 lbs (0.7 – 3.7 kg) weight gain |
| Lixisenatide (Adlyxin) [Ref] | ⇓ 2.9 – 6 lbs (-1.36 to – 2.7 kg) weight loss |
| Soliqua | 0.3 kg weight loss vs 1.1 kg weight gain with Glargine alone |
It is obvious that Xultophy is associated with less weight gain when compared to Insulin Degludec. Similarly, Soliqua is associated with less weight gain compared to insulin glargine.
How safe is Xultophy Vs Soliqua?
Insulin and GLP-1 analogs have their side effects. The major side effect of Insulin is hypoglycemia while GLP-1 cause significant GI side effects including constipation, nausea, bloating, pancreatitis, and injection site reactions.
Risk of Hypoglycemia with Injection Xultophy and Soliqua:
Medications | Risk of Severe or Documented Symptomatic Hypoglycemia |
| Xultophy | 0 to 0.5% [Ref] |
| Soliqua | 1.1 to 40% [Ref] |
In the FDA prescribing information, severe hypoglycemia and symptomatic documented hypoglycemia have been documented more with Soliqua Vs Xultophy.
The frequency of severe hypoglycemia is mentioned in the table above.
Injection-site reactions with Injection Xultophy Vs Soliqua:
Medications | Injection-site reactions |
| Xultophy | 2.6% |
| Soliqua | 1.7% |
As mentioned in the table above, injection site reactions are more common with Xultophy compared to Soliqua.
GI side effects of Injection Xultophy Vs Soliqua:
The two common GI side effects mentioned in the FDA prescribing information for both Xultophy and Soliqua are nausea and diarrhea.
It can be seen in the table below that Soliqua is associated with a slightly greater percentage of nausea compared to Xultophy.
GI Side Effects | Xultophy | Soliqua |
| Nausea | 7.8% | 10% |
| Diarrhea | 7.5% | 7% |
| Vomiting | <5% | <5% |
| Constipation | <5% | <5% |
| Dyspepsia | <5% | <5% |
| Abdominal pain | <5% | <5% |
What are the PROS and CONS of Xultophy Vs Soliqua?
The PROS and CONS of Xultophy Vs Soliqua are summarized in the table below:
PROS and CONS | Xultophy | Soliqua |
| Dosing | Once daily | Once daily |
| Titration | one unit insulin Degludec and 0.036 mg Liraglutide | one unit insulin Glargine and 0.33 mg Lixisenatide |
| HbA1C reduction [Ref] | -1.05% Vs Insulin Degludec-0.59% Vs Insulin Glargine | -0.52% Vs Insulin Glargine |
| Body weight | -2.51 kg Vs Insulin Degludec-3.20 kg Vs Insulin Glargine | -1.37 kg Vs Insulin Glargine |
| Daily Insulin Dose reduction | 0 units Vs Insulin Degludec-25.5 units Vs Insulin Glargine | -0.3 units Vs Insulin Glargine |
| Severe Hypoglycemia | 0.66 Vs Insulin Degludec0.43 Vs Insulin Glargine | ORR 1.0 Vs Glargine |
| Injection site reactions | More | Fewer |
| GI side effects | Less | More |
It is clear from the table above that Xultophy is a better fixed-dose combination of long-acting basal insulin and a long-acting GLP-1 analog.
Xultophy is associated with greater weight loss and is more effective in lowering the A1C. In addition, not mentioned here, Lixisenatide, the GLP-1 in SOLIQUA, has no added cardiovascular benefits compared to Liraglutide, the GLP-1 in Xultophy
Conclusion: Choosing the Right Option for You
From the above discussion, it seems that Xultophy has superior glycemic efficacy, fewer gastrointestinal side effects, and less weight gain compared to Soliqua.
However, Soliqua is associated with fewer injection-site reactions compared to Xultophy.
Both Xultophy and Soliqua are administered once daily and dose titration is very fine-tuned allowing greater A1C reduction without an additional risk of hypoglycemia.
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