Adlyxin (Lixisenatide) Drug Interactions: What to Avoid and What to Tell Your Doctor

Adlyxin (lixisenatide) was discontinued in the US in January 2023, but its drug interaction profile remains relevant for anyone taking Soliqua 100/33 (which contains lixisenatide) or transitioning to another GLP-1 receptor agonist. Understanding lixisenatide's interactions helps you have an informed conversation with your doctor when switching to any GLP-1 alternative, since many of the same interaction principles apply across the class.

Why Lixisenatide Had So Many Drug Interactions: The Gastric Emptying Effect

The root cause of most lixisenatide drug interactions was its potent inhibition of gastric emptying — slowing how quickly food (and oral medications) left the stomach and were absorbed. When you take an oral medication with food, gastric emptying affects how fast and how completely that drug is absorbed into the bloodstream. Lixisenatide's strong gastric slowing could delay absorption, reduce peak concentrations, and alter the timing of a drug's effect.

Major Interactions: Sulfonylureas and Basal Insulin (Hypoglycemia Risk)

The most clinically significant interactions of lixisenatide were with sulfonylureas (e.g., glimepiride, glipizide) and basal insulin:

Sulfonylureas: When patients on a sulfonylurea added lixisenatide, symptomatic hypoglycemia occurred in 14.5% of Adlyxin patients vs 10.6% on placebo. Sulfonylurea dose reduction was often required

Basal insulin: When lixisenatide was combined with basal insulin (with or without a sulfonylurea), hypoglycemia occurred in 47.2% of Adlyxin patients compared to 21.6% for placebo. Insulin dose reduction was frequently needed

These interactions require dose adjustment to prevent dangerous low blood sugar events. The same risk applies with any GLP-1 receptor agonist added to a sulfonylurea or insulin regimen.

Moderate Interactions: Oral Contraceptives

Because lixisenatide slowed gastric emptying, it could delay absorption of oral contraceptives — potentially reducing their peak blood concentration and altering their efficacy. The FDA-approved prescribing information required that:

Oral contraceptives should be taken at least 1 hour before lixisenatide injection OR at least 11 hours after the lixisenatide dose

This was particularly important because altered contraceptive absorption could affect pregnancy prevention reliability. Women taking hormonal contraceptives who are starting a GLP-1 agent should discuss timing with their prescriber.

Moderate Interactions: Oral Antibiotics and Time-Critical Medications

Oral medications that depend on threshold concentrations for efficacy — particularly antibiotics — needed to be taken at least 1 hour before lixisenatide injection. If an antibiotic's absorption was delayed and its peak concentration fell below the minimum inhibitory concentration needed to fight infection, it could be less effective.

Similarly, medications where a delay in effect is undesirable (such as pain relievers taken for breakthrough pain) should be timed before the lixisenatide injection. This applies similarly to other GLP-1 agents that slow gastric emptying.

Minor Interactions: Acetaminophen (Tylenol)

Clinical studies showed that when acetaminophen was administered 1 or 4 hours after lixisenatide, its maximum concentration (Cmax) was decreased by 29% and 31% respectively, and median time to peak (Tmax) was delayed by 1.75 to 2 hours. However, when acetaminophen was taken 1 hour before lixisenatide, no effect on Cmax or Tmax was observed. No effects on overall exposure (AUC) were noted, meaning the total amount absorbed was not changed — only the timing and peak were affected.

Other Noted Pharmacokinetic Interactions

Digoxin: Overall exposure (AUC) was not affected; however, the time to peak concentration (Tmax) was delayed by 1.5 hours when co-administered with lixisenatide

Ramipril (ACE inhibitor): AUC was increased by 21% while Cmax was decreased by 63%. The AUC and Cmax of the active metabolite ramiprilat were not affected. This interaction was not considered clinically significant but is worth noting

Atorvastatin: Cmax was decreased by 31% and Tmax was delayed by 3.3 hours when atorvastatin was administered with lixisenatide; AUC was not affected

Medications to Tell Your Doctor About Before Starting Any GLP-1

Before starting lixisenatide or any GLP-1 receptor agonist, tell your doctor if you take any of the following:

Sulfonylureas (glimepiride, glipizide, glyburide, glipizide, etc.)

Any form of insulin (basal, rapid-acting, premixed)

Oral contraceptives or other hormonal contraception

Antibiotics or other medications requiring consistent blood concentration

Warfarin or other blood thinners (GLP-1-induced GI changes can affect INR monitoring timing)

Thyroid medications (levothyroxine) — timing should be optimized relative to GLP-1 injection

For more on managing side effects on GLP-1 therapy, see our Adlyxin side effects guide. If you are looking for a GLP-1 alternative to Adlyxin, review our Adlyxin alternatives guide for the best options in 2026.