Evidence Grade A — Regulatory approved. 706 published studies. 60 registered clinical trials.
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Lixisenatide (sold as Adlyxin) is a once-daily injectable GLP-1 treatment for type 2 diabetes that primarily works by slowing the rate at which food leaves the stomach, making it particularly effective at controlling blood sugar spikes after meals. As a standalone product, it has been largely overtaken by more powerful alternatives, but it continues in use as part of the combination product Soliqua (lixisenatide plus insulin glargine).
Lixisenatide is also known by these brand and alternate names:
706 published studies: 472 human, 37 animal, 13 in-vitro, 283 reviews
Lixisenatide was marketed as Adlyxin in the US (approved July 2016), though it has since been discontinued in the US market. The ELIXA cardiovascular trial, involving over 6,000 patients, was the first cardiovascular outcomes trial for any GLP-1 medication to report results. It showed a neutral cardiovascular profile — neither harmful nor beneficial — meeting safety requirements but not demonstrating the heart benefits later shown by semaglutide and liraglutide.
Lixisenatide found its primary clinical role in combination with basal insulin, marketed as Soliqua (lixisenatide plus insulin glargine). This combination addresses both fasting blood sugar (via insulin) and post-meal spikes (via lixisenatide) in a single daily injection. As a standalone treatment, it has been largely superseded by more potent GLP-1 medications.
Lixisenatide targets the same GLP-1 receptor as other medications in this class, but because it is shorter-acting, its main effect is dramatically slowing the rate at which food leaves the stomach. This flattens the blood sugar spike that typically follows a meal. It also promotes some insulin release and reduces glucagon, but these effects are less pronounced than with longer-acting GLP-1 treatments. This makes lixisenatide particularly suited for people whose main challenge is post-meal blood sugar control rather than overall blood sugar levels.
Lixisenatide's main contribution to the evidence base was the ELIXA trial — the first cardiovascular outcomes study completed for any GLP-1 medication, involving over 6,000 patients. It showed a neutral cardiovascular profile (neither harmful nor beneficial), which was adequate for safety but did not match the heart benefits later demonstrated by semaglutide, liraglutide, and dulaglutide. As a standalone agent, lixisenatide was discontinued from the US market because it offered limited advantages over newer, more effective GLP-1 treatments. Its ongoing relevance is as the GLP-1 component in the Soliqua combination product, where its ability to control post-meal blood sugar spikes complements the all-day fasting glucose coverage provided by insulin glargine — addressing two different parts of the blood sugar problem in a single daily injection.
PeptideTrace tracks 60 registered clinical trials for Lixisenatide sourced from ClinicalTrials.gov.
Regimen Transition After Short-Term Intensive Insulin Therapy in Type 2 Diabetes
Efficacy and Safety of iGlarLixi Versus Standard of Care in a Real-world Adult China Population With Uncontrolled Type 2 Diabetes on Oral Agents
Evaluation of the Efficacy and Safety of GLP-1 Receptor Agonist Therapy In Steroid-Induced Diabetes
A Study to Investigate Safety and Efficacy of iGlarLixi in Adult Patients With Type 2 Diabetes Mellitus
iGlarLixi CGM Study in Chinese T2D Individuals After OADs
EMA Marketing Authorisation
FDA ORIG 1
FDA SUPPL 2
FDA SUPPL 3
Health Canada Market Authorisation
FDA SUPPL 7
FDA SUPPL 9
FDA SUPPL 8
FDA SUPPL 11
FDA SUPPL 12
FDA SUPPL 13
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FDA SUPPL 18
Lixisenatide is a 44-amino-acid exendin-4 derivative classified as a short-acting GLP-1 receptor agonist. It primarily targets postprandial glucose excursions rather than providing sustained GLP-1 receptor activation. It is administered once daily via subcutaneous injection.
Lixisenatide activates the GLP-1 receptor via the Gs/cAMP pathway. As a short-acting GLP-1 RA, it predominantly slows gastric emptying (its dominant mechanism for postprandial glucose control) with less sustained insulin secretion enhancement compared to long-acting agents. This pharmacological profile complements basal insulin therapy, leading to its use in fixed-ratio combination with insulin glargine.
Lixisenatide was marketed as Adlyxin in the US (approved July 27, 2016). The ELIXA trial (N=6,068; the first GLP-1 RA cardiovascular outcomes trial to report) demonstrated a neutral cardiovascular result with MACE HR 1.02 (95% CI 0.89–1.17), meeting noninferiority but showing no superiority. Adlyxin standalone marketing was discontinued on January 1, 2023 (Sanofi business decision; NDA remains active). Lixisenatide remains available as a component of Soliqua 100/33 (insulin glargine + lixisenatide, approved November 21, 2016), a fixed-ratio combination targeting both fasting and postprandial glucose.
Linaclotide is marketed as Linzess (approved August 2012). It is taken as a daily oral capsule on an empty stomach, at least 30 minutes before the first meal. The recommended dose is 290 mcg for IBS-C and 72 or 145 mcg for chronic constipation. In clinical trials, approximately 34% of IBS-C patients met the composite improvement endpoint compared to 17% on placebo. Diarrhoea is the most common side effect (approximately 20%) and the leading reason for discontinuation. Linaclotide has a boxed warning against use in children under 6 years due to deaths in young mice, though no such events have been reported in humans. It competes with plecanatide (which targets the same pathway) and other IBS-C treatments.
Elamipretide (Forzinity) was approved by the FDA for Barth syndrome based on the TAZPOWER trial. The randomised crossover phase (12 patients) did not meet its primary endpoints, but the open-label extension (168 weeks) demonstrated durable improvements in walking distance and muscle strength that formed the basis for approval. Barth syndrome affects approximately 1 in 300,000–400,000 births. A larger Phase III trial in primary mitochondrial myopathy (218 patients, MMPOWER-3) did not meet its primary endpoint, and the drug was not approved for that broader indication. Elamipretide remains approved exclusively for Barth syndrome. See also SS-31 (#158) for the research compound context.
Glucagon has been available as an emergency injection since the 1960s and remains the standard rescue treatment for severe hypoglycaemia. Recent innovation has focused on making it easier to administer in emergencies. Baqsimi, approved in 2019, was the first needle-free option as a nasal powder. Gvoke, also approved in 2019, eliminated the need to mix and reconstitute the medication before injection — a significant advance since severe hypoglycaemia often impairs the ability to follow complex preparation steps. Dasiglucagon (Zegalogue), a next-generation stable liquid glucagon approved in 2021, further improved on the convenience of rescue administration. Beyond emergency rescue, glucagon's receptor is now a major research target — dual and triple agonists combining glucagon receptor activity with GLP-1 (such as survodutide and retatrutide) are in advanced clinical trials for obesity and metabolic disease.
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