Insulin degludec / liraglutide (IDegLira)
Insulin degludec and liraglutide in a fixed ratio, dosed together in one daily injection
IDegLira combines a long-acting insulin and a GLP-1 drug in a fixed ratio, so each dose step adds one unit of insulin and 0.036 mg of liraglutide. In its trials it lowered HbA1c more than either component alone with less nausea than liraglutide. The liraglutide in it carries a boxed thyroid warning.
What is it?
Insulin lowers blood sugar powerfully but tends to add weight and cause hypoglycaemia; GLP-1 drugs lower it more gently, cut appetite and cause nausea. IDegLira puts the two in one pen at a fixed ratio, so titrating the insulin automatically titrates the liraglutide, and the slow build-up softens the nausea. Each unit carries 1 unit of degludec and 0.036 mg of liraglutide; the label starts people new to either drug at 10 units, those already on one at 16, and caps the dose at 50 units, which is 1.8 mg of liraglutide.
The founding trial, DUAL I, randomised 1,663 adults to IDegLira, degludec alone or liraglutide alone for 26 weeks. HbA1c fell 1.9 points on the combination against 1.4 on degludec and 1.3 on liraglutide, and nausea affected 8.8% on IDegLira against 19.7% on liraglutide. Across six trials it lowered HbA1c about 0.8 points more than degludec alone.
Later trials extended it. DUAL IV added it to sulphonylureas against placebo, and 79.2% reached an HbA1c under 7%. A 52-week trial in 819 Japanese patients and DUAL II China, in people on basal insulin, both found it superior to its components. In people with HbA1c near 11%, it lowered HbA1c just as much with half the hypoglycaemia and far less weight gain.
Much of its use is simplification. Older adults switched from complex insulin regimens kept or improved control with far fewer lows; patients leaving hospital did better on it than on four injections a day; and an Italian cohort stayed on it for four years with lasting HbA1c reductions. A once-weekly successor combining insulin icodec with semaglutide is estimated, indirectly, to outperform it.
Because liraglutide is in it, Xultophy carries liraglutide's boxed warning: liraglutide causes thyroid C-cell tumours in rodents, and the drug is contraindicated in people with a personal or family history of medullary thyroid carcinoma. Previous liraglutide or basal insulin is stopped before starting it.
Mechanism of Action
IDegLira is a fixed-ratio pen of ultra-long-acting insulin degludec and the GLP-1 agonist liraglutide.
Degludec
Ultra-long-acting basal insulin; half-life about 25 hours (label 12.3).
Liraglutide
GLP-1 agonist that lowers post-meal glucose and appetite; half-life about 13 hours.
Fixed ratio
Each unit: 1 unit degludec and 0.036 mg liraglutide, so both rise together (label 2.1).
Published Research
These are the trials that describe IDegLira, read from their PubMed abstracts: four randomised phase 3 trials.
DUAL I: against its components
1,663 insulin-naive adults took IDegLira, degludec or liraglutide 1.8 mg for 26 weeks. HbA1c fell 1.9 points against 1.4 and 1.3; IDegLira was non-inferior to degludec and superior to liraglutide, with nausea in 8.8% against 19.7% on liraglutide.
DUAL IV: on top of sulphonylureas
435 adults uncontrolled on sulphonylurea with or without metformin took IDegLira or placebo for 26 weeks, double-blind. HbA1c fell from 7.9% to 6.4% against 7.4% on placebo, and 79.2% reached under 7%.
52 weeks in Japan
819 Japanese adults uncontrolled on one oral drug took IDegLira, liraglutide 1.8 mg or degludec for 52 weeks. HbA1c fell 26 mmol/mol on IDegLira against 20 on either component, confirming superiority.
DUAL II China: from basal insulin
453 Chinese adults uncontrolled on basal insulin and metformin were randomised 2:1 to IDegLira or degludec, both capped at 50 units, for 26 weeks, testing HbA1c, weight and hypoglycaemia.
Against basal-bolus in very high HbA1c
In 145 adults with type 2 diabetes and HbA1c around 10.8%, IDegLira lowered HbA1c as much as basal-bolus insulin (3.18 against 3.00 points) with less hypoglycaemia (26% against 48%) and less weight gain (1.2 against 5.8 kg).
From hospital to home
In 64 patients leaving hospital with very high HbA1c (11.6%), IDegLira caused fewer hypoglycaemic events than multiple daily injections (6.2% against 31.3% with at least one) on continuous glucose monitoring.
Simplifying in older adults
In 96 older adults (mean 77) mostly on basal-bolus insulin, switching to IDegLira lowered fasting glucose and HbA1c at 6 months while level 1 and 2 hypoglycaemia fell sharply.
Four years of real-world use
In 156 Italian patients starting IDegLira, HbA1c was 1.34 points lower after 48 months in those coming from basal-oral therapy and 1.07 lower in those coming from basal-bolus; mealtime insulin was stopped in the first week.
Against degludec alone: six trials
Across six trials of 3,393 patients, IDegLira lowered HbA1c 0.79 points more than degludec alone, and weight 1.6 kg more.
Against weekly IcoSema
A network meta-analysis estimated that once-weekly insulin icodec plus semaglutide would lower HbA1c 0.4 points more than daily IDegLira, with 3.2 kg more weight loss and fewer serious lows; no head-to-head trial exists.
Dosing Data
Xultophy 100/3.6 is injected once daily at the same time, with or without food, starting at 10 or 16 units and titrated up to 50.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the Xultophy label and the trials above.
Contraindications & Cautions
Set by the label.
Legal Status
IDegLira is approved in the US as Xultophy 100/3.6.
Frequently Asked Questions
?What is IDegLira?
Insulin degludec and liraglutide combined in a fixed ratio in one daily injection, sold as Xultophy 100/3.6.
?Why combine them?
They lower blood sugar in different ways. In DUAL I the combination lowered HbA1c more than either alone, with less nausea than liraglutide.
?What dose is used?
The label starts at 10 units for people new to both drugs and 16 for those already on one, up to 50 units a day.
?Why the boxed warning?
Its liraglutide component causes thyroid C-cell tumours in rodents, so it is contraindicated with a history of medullary thyroid cancer.
?Do I stop my other insulin or GLP-1 drug first?
Yes. The label says to discontinue liraglutide or basal insulin before starting Xultophy, beginning at 16 units if you were on either, or 10 units if on neither.
References
- [fda-pi] Xultophy 100/3.6 (insulin degludec and liraglutide) injection Prescribing Information, sections 1 and 2 (DailyMed version 14, effective October 14, 2025; read September 30, 2026).
- [pubmed] Gough SC, et al. "Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes." Lancet Diabetes Endocrinol, 2014;2(11):885-93. PMID: 25190523.
- [pubmed] Rodbard HW, et al. "Safety and efficacy of insulin degludec/liraglutide (IDegLira) added to sulphonylurea alone or to sulphonylurea and metformin in insulin-naïve people with Type 2 diabetes: the DUAL IV trial." Diabet Med, 2017;34(2):189-196. PMID: 27589252.
- [pubmed] Kaku K, et al. "Superior efficacy with a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with insulin degludec and liraglutide in insulin-naïve Japanese patients with type 2 diabetes in a phase 3, open-label, randomized trial." Diabetes Obes Metab, 2019;21(12):2674-2683. PMID: 31407845.
- [pubmed] Pei Y, et al. "DUAL II China: Superior HbA1c reductions and weight loss with insulin degludec/liraglutide (IDegLira) versus insulin degludec in a randomized trial of Chinese people with type 2 diabetes inadequately controlled on basal insulin." Diabetes Obes Metab, 2021;23(12):2687-2696. PMID: 34387411.
- [clinical-trial] Galindo RJ, et al. "A Randomized Controlled Trial Comparing the Efficacy and Safety of IDegLira Versus Basal-Bolus in Patients With Poorly Controlled Type 2 Diabetes and Very High HbA1c ≥9-15%: DUAL HIGH Trial." Diabetes Care, 2023;46(9):1640-1645. PMID: 37459574.
- [pubmed] Liu Y, et al. "IDeglira vs insulin degludec for type 2 diabetes: a systematic review and meta-analysis." Front Endocrinol (Lausanne), 2025;16:1643386. PMID: 40958912.
- [clinical-trial] Gómez-Medina AM, et al. "Insulin DEgludec/LIraglutide versus multiple daily insulin injections in the transition from hospital to outpatient management assessed by continuous glucose monitoring: the DELI transition trial." Diabetologia, 2025;68(9):1899-1907. PMID: 40760249.
- [pubmed] De Fano M, et al. "The impact of ideglira in treatment simplification in older adults with type 2 diabetes mellitus already on insulin therapy: The stop study." Diabetes Res Clin Pract, 2025;223:112119. PMID: 40174863.
- [pubmed] Di Loreto C, et al. "Effectiveness, Simplification and Persistence of IDegLira in Poorly Controlled People with Type 2 Diabetes: A 4-Year Follow-Up Real-World Study." Diabetes Ther, 2024;15(6):1313-1331. PMID: 38605275.
- [pubmed] Kandalam S, et al. "Efficacy and Safety of Once-Weekly IcoSema Versus Once-Daily IDegLira in People with Type 2 Diabetes: Systematic Literature Review and Network Meta-analysis." Diabetes Ther, 2026;17(4):547-561. PMID: 41762380.
- [fda-pi] Xultophy 100/3.6 (insulin degludec and liraglutide) injection US prescribing information (DailyMed set 21335fe4, effective October 14, 2025), sections 2.1-2.2; read through openFDA October 6, 2026.
Sources & Citations
Studies were read from their PubMed abstracts; the Xultophy label from DailyMed (set 21335fe4, effective October 14, 2025) through openFDA, read October 6, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.