Lixisenatide
The short-acting GLP-1 drug that proved cardiovascular safety and found a second life in Parkinson's
Lixisenatide is a once-daily GLP-1 receptor agonist approved in 2016. Its own cardiovascular trial showed no benefit and no harm, and its most interesting recent result is in a different disease: slower progression of motor disability in early Parkinson's.
What is it?
Lixisenatide arrived late into a crowded class and was always the short-acting one. Its terminal half-life is about 3 hours, so a once-daily dose acts mainly on glucose after meals rather than fasting glucose, which is why it is paired with a basal insulin in a fixed combination.
The mechanism is the stomach. In 30 metformin-treated patients, eight weeks of lixisenatide more than doubled how long a glucose drink stayed in the stomach, and the fall in post-meal glucose tracked how much emptying slowed. Against liraglutide, it lengthened gastric emptying half-time by 52 minutes against 25, without more reflux.
Its cardiovascular outcomes trial, ELIXA, is a clean null: in people with type 2 diabetes and a recent acute coronary syndrome, adding lixisenatide did not significantly change major cardiovascular events, and did not raise serious adverse events, severe hypoglycaemia, pancreatitis, pancreatic neoplasms or allergic reactions against placebo.
The fixed combination with insulin glargine is where it is still used in the US. In 521 patients, the combination lowered HbA1c by 1.40% against 0.76% on glargine alone, with 71.5% against 38.5% reaching below 7% and about 1 kg less weight gain; matched against basal-bolus insulin, it caused about a third as many hypoglycaemia events. A network meta-analysis found no HbA1c difference between it and the degludec-liraglutide combination, though no head-to-head trial exists.
Smaller trials found limits: it did not soften arteries in kidney disease or improve time in range in type 1 diabetes, while in adolescents with type 2 diabetes it improved glucose with mostly gastrointestinal side effects.
The result that put it back in the news is neurological. In LIXIPARK, a phase 2 trial in early Parkinson's disease, lixisenatide produced less progression of motor disability at 12 months than placebo, at the cost of nausea in 46% and vomiting in 13% of participants. That use is investigational.
Adlyxin, the lixisenatide-only pen, left the US market at the start of 2023, so lixisenatide is now available in the US only inside Soliqua 100/33, dosed in units of insulin glargine with lixisenatide carried along at a fixed ratio.
Mechanism of Action
Lixisenatide is a short-acting GLP-1 receptor agonist whose main lever on glucose is slowing the stomach.
GLP-1 receptor
Activates the GLP-1 receptor; after oral glucose it suppressed glucagon and insulin (2020 dual-tracer study).
Slower gastric emptying
More than doubled gastric retention of a glucose drink after 8 weeks; post-meal glucose fell with it (2020 study).
Short-acting
Terminal half-life about 3 hours after repeated doses (Soliqua label 12.3).
Published Research
The trials behind lixisenatide, read from their PubMed abstracts: ELIXA, the glargine combination and its comparison with basal-bolus insulin, add-on and mechanism studies, a comparison with liraglutide, trials in kidney disease, adolescents and type 1 diabetes, LIXIPARK, and a network meta-analysis. Dosing from the Soliqua label read October 6, 2026.
A clean null on the heart
In ELIXA, in people with type 2 diabetes and a recent acute coronary syndrome, adding lixisenatide to usual care did not significantly alter the rate of major cardiovascular events, and was not associated with more serious adverse events, severe hypoglycaemia, pancreatitis, pancreatic neoplasms or allergic reactions than placebo.
The fixed combination with glargine
In 521 patients, the glargine-lixisenatide combination lowered HbA1c by 1.40% against 0.76% on glargine alone, with 71.5% against 38.5% reaching HbA1c below 7% and about 1 kg less weight gain.
Fixed combination against basal-bolus insulin
Matching 195 patients on the glargine-lixisenatide combination with 195 on basal-bolus insulin from another trial, the combination gave slightly more HbA1c reduction (0.28%), 1.32 kg less weight gain and about a third as many hypoglycaemia events, with more gastrointestinal effects.
Added to basal insulin
Adding once-daily lixisenatide to basal insulin significantly reduced HbA1c and two-hour post-meal glucose, with an HbA1c reduction of 0.56% in Asian and 0.41% in white participants after adjustment, and no difference in treatment effect between the populations.
How it lowers post-meal glucose
In 30 metformin-treated patients, 8 weeks of lixisenatide 20 µg daily more than doubled gastric retention of a glucose drink (AUC ratio 2.19) and slowed glucose entry into the blood; the fall in post-meal glucose tracked how much gastric emptying slowed.
Against liraglutide: stomach and oesophagus
In 57 patients randomised for 10 weeks, gastric emptying half-time lengthened by 52 minutes on lixisenatide and 25 on liraglutide, with no difference in reflux episodes or oesophageal motility.
What it does to blood fats
Lixisenatide reduced chylomicron triacylglycerol by increasing clearance, a metabolic effect beyond glucose.
Arterial stiffness in kidney disease
In 90 analysed people with type 2 diabetes and chronic kidney disease, 24 weeks of lixisenatide lowered HbA1c against placebo but did not change aortic pulse-wave velocity (9.65 against 9.96 m/s), albuminuria or Klotho.
Adolescents with type 2 diabetes
In 10- to 17-year-olds, once-daily lixisenatide (5 to 20 µg) improved glucose, HbA1c and weight against placebo; vomiting and nausea each affected 11.1%, with no symptomatic hypoglycaemia.
Type 1 diabetes: no gain in time in range
In 25 adults with type 1 diabetes, four weeks of added lixisenatide did not raise post-meal time in range or lower HbA1c, though meal-test glucose, glucagon and mealtime insulin fell.
Slower motor decline in early Parkinson's
In LIXIPARK, a phase 2 trial in early Parkinson's disease, lixisenatide produced less progression of motor disability than placebo at 12 months, with nausea in 46% of participants and vomiting in 13%.
The two fixed combinations compared
A network meta-analysis of 29 trials found no direct head-to-head trial and no HbA1c difference between the glargine-lixisenatide and degludec-liraglutide combinations (0.10%), both beating their components.
Dosing Data
In the US lixisenatide is available only in Soliqua 100/33, dosed once daily in units of insulin glargine within an hour before the first meal, titrated to fasting glucose.
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 trials above.
Contraindications & Cautions
Standard for the class.
Legal Status
Approved for diabetes only.
Frequently Asked Questions
?How does lixisenatide differ from the other GLP-1 drugs?
It is short-acting and once-daily, with its main effect on glucose after meals rather than fasting glucose, which is why it is paired with a basal insulin.
?What did its cardiovascular trial show?
ELIXA found no significant change in major cardiovascular events after a recent acute coronary syndrome, and no excess of serious adverse events against placebo.
?Is it a Parkinson's treatment?
Not an approved one. A phase 2 trial found less progression of motor disability at 12 months, with nausea in 46% of participants.
?Why is it combined with insulin glargine?
Its post-meal action complements a basal insulin's fasting control, which is what the fixed-ratio product is for.
?Can I still get lixisenatide on its own?
Not in the US: Sanofi stopped selling Adlyxin from January 1, 2023. It remains available inside Soliqua 100/33.
?How long does it last?
The Soliqua label gives a terminal half-life of about 3 hours after repeated doses, which is why its effect is mostly on the meal after dosing.
?Why does it slow the stomach so much?
Short-acting GLP-1 drugs keep slowing gastric emptying with daily use; in one trial it lengthened emptying half-time by 52 minutes, against 25 for liraglutide.
?Is it better than the degludec-liraglutide combination?
No trial has compared them directly; a network meta-analysis found similar HbA1c lowering.
References
- [pubmed] Pfeffer MA, et al. "Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome." N Engl J Med, 2015;373(23):2247-57. PMID: 26630143.
- [pubmed] Meissner WG, et al. "Trial of Lixisenatide in Early Parkinson's Disease." N Engl J Med, 2024;390(13):1176-1185. PMID: 38598572.
- [pubmed] Liu F, et al. "Efficacy of once-daily glucagon-like peptide-1 receptor agonist lixisenatide as an add-on treatment to basal insulin in Asian and white adults with type 2 diabetes mellitus: An individual-level pooled analysis of phase III studies." J Diabetes Investig, 2021;12(8):1386-1394. PMID: 33475222.
- [pubmed] Terauchi Y, et al. "Efficacy and safety of insulin glargine/lixisenatide fixed-ratio combination (iGlarLixi 1:1) in Japanese patients with type 2 diabetes mellitus inadequately controlled on oral antidiabetic drugs: A randomized, 26-week, open-label, multicentre study: The LixiLan JP-O2 randomized clinical trial." Diabetes Obes Metab, 2020;22 Suppl 4:14-23. PMID: 32291880.
- [pubmed] Whyte MB, et al. "Lixisenatide Reduces Chylomicron Triacylglycerol by Increased Clearance." J Clin Endocrinol Metab, 2019;104(2):359-368. PMID: 30215735.
- [fda-pi] Adlyxin (lixisenatide) Prescribing Information. Sanofi.
- [manufacturer] Sanofi. Adlyxin healthcare-professional site: 'As of January 01, 2023, Adlyxin will no longer be available in the US.' Read October 5, 2026.
- [clinical-trial] Fountoulakis N, et al. "Effect of lixisenatide on arterial stiffness in people with type 2 diabetes and kidney disease: Results of a randomised controlled trial." Diabetes Obes Metab, 2026;28(4):2953-2961. PMID: 41705420.
- [clinical-trial] Barrientos-Pérez M, et al. "A study on pharmacokinetics, pharmacodynamics and safety of lixisenatide in children and adolescents with type 2 diabetes." Pediatr Diabetes, 2022;23(6):641-648. PMID: 35411611.
- [clinical-trial] Ballav C, et al. "Lixisenatide in type 1 diabetes: A randomised control trial of the effect of lixisenatide on post-meal glucose excursions and glucagon in type 1 diabetes patients." Endocrinol Diabetes Metab, 2020;3(3):e00130. PMID: 32704555.
- [clinical-trial] Rayner CK, et al. "Effects of Sustained Treatment With Lixisenatide on Gastric Emptying and Postprandial Glucose Metabolism in Type 2 Diabetes: A Randomized Controlled Trial." Diabetes Care, 2020;43(8):1813-1821. PMID: 32471908.
- [clinical-trial] Quast DR, et al. "Effects of Lixisenatide Versus Liraglutide (Short- and Long-Acting GLP-1 Receptor Agonists) on Esophageal and Gastric Function in Patients With Type 2 Diabetes." Diabetes Care, 2020;43(9):2137-2145. PMID: 32647054.
- [pubmed] Tabák ÁG, et al. "Efficacy and Safety of iGlarLixi, Fixed-Ratio Combination of Insulin Glargine and Lixisenatide, Compared with Basal-Bolus Regimen in Patients with Type 2 Diabetes: Propensity Score Matched Analysis." Diabetes Ther, 2020;11(1):305-318. PMID: 31848983.
- [pubmed] Visolyi GÁ, et al. "Comparison of Efficacy and Safety of Commercially Available Fixed-Ratio Combinations of Insulin Degludec/Liraglutide and Insulin Glargine/Lixisenatide: A Network Meta-analysis." Can J Diabetes, 2023;47(4):368-377. PMID: 36963632.
- [fda-pi] Soliqua 100/33 (insulin glargine and lixisenatide) injection US prescribing information (DailyMed, revised March 2026), sections 2.2 and 12.3; read October 6, 2026.
Sources & Citations
Trials were read from their PubMed abstracts on October 1, 2026; approvals from Drugs@FDA the same day.
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.