Lixisenatide

Lixisenatide was discontinued in the U.S. in 2023
1. Soliqua (Lixisenatide combined with Insulin Glargine) is still available

See GLP-1 Agonist
Type II Diabetes Mellitus
1. Very effective for weight loss in comorbid Obesity
2. May be used in combination with Basal insulin (e.g. Lantus)
Insulin deficiency and Insulin Resistance
1. Adjunct to Glucophage, Sulfonylureas, Glitazones
Weight Loss
1. At least 50% of weight regained on stopping GLP-1 agents

See GLP-1 Agonist
Type I Diabetes Mellitus
Medullary Thyroid Carcinoma (personal or Family History)
Multiple Endocrine Neoplasia syndrome type 2 (active)
Concurrent prandial Insulin (Bolus Insulin)
1. Basal insulin (e.g. Lantus) may be used
Severe Gastrointestinal Diseases or Gastroparesis
1. Relative contraindication due to the high Incidence of gastrointestinal side effects with GLP-1 Agonists
Severe Chronic Kidney Disease Stage 5 (eGFR <15 ml/min)

Precautions
1. All GLP-1 Agonists are expensive ($600 to $1300 per month in 2024)
2. GLP-1 shortages (esp. Semaglutide and Tirzepatide) have resulted in many online resellers
  1. Buy from only licensed pharmacies (U.S.), and appropriately accredited (e.g. compounding pharmacy)
  2. Certificates of analysis confirm active ingredient
Lixisenatide (Adlyxin)
1. Newer agent of the class (released in 2017)
2. Once daily injection dosing
3. Available in multidose 3 ml pens: 10 mcg dose (50 mcg/ml) or 20 mcg dose (100 mcg/ml)
Combination: Insulin Glargine with Lixisenatide (Soliqua)
1. Addition of Lixisenatide, may spare basal Insulin Dosing
2. However, limits titration of basal Insulin Dosing (fixed dose combinations)
3. Very expensive ($760 to 950 per month in 2024)

Give subcutaneous doses in the upper arm, Abdomen or thigh (and rotate injection sites)
Administer injection within 1 hour of first meal of day
Start 10 mg SQ daily
May increase to 20 mg SQ daily after 14 days

See GLP-1 Agonist
Nausea or Vomiting
1. Eat smaller meals and more slowly, stopping before fullness (satiety)
2. Consider short-term Ondansetron
3. Consider dose reduction until tolerated
Diarrhea
Dizziness
Headache
Hypoglycemia
1. Alone, GLP-1 Agonists do not significantly increase risk of Hypoglycemia
2. Avoid combination with Bolus Insulin (Mealtime Insulin) or Insulin Secretagogues (e.g. Sulfonylureas)
3. With Sulfonylurea: 14.4% at 5 mcg, 35.7% at 10 mcg
4. With Metformin: 4.5% at 5 mcg, 5.3% at 10 mcg
Pancreatitis (occurs with all GLP-1 Agonists)
1. Singh (2013) JAMA Intern Med 173(7):534-9 [PubMed]
Gallbladder disease (Cholelithiasis, Cholecystitis, Choledocholithiasis)
1. Increased by one in 357 patients over 3 years of medication use
2. Increased with longer use, higher dose and when GLP-1 Agonist is used for weight loss
3. Faillie (2016) JAMA Intern Med 176(10): 1474-81 +PMID: 27478902 [PubMed]
Subcutaneous Fat Loss
1. Desired weight loss (esp. Semaglutide) may result in loose, sagging skin ("Ozempic face")
Other serious but uncommon effects (<1%)
1. Acute Kidney Injury
2. Angioedema
3. Suicidality (case reports, FDA is investigating as of 2024)

Unknown safety in Lactation
Most GLP-1 Agonists have unknown safety in pregnancy (avoid)
1. High dose weight loss GLP-1 Agonists (e.g. Saxena, Wegovy) are considered Pregnancy Category X

Avoid using 2 Incretins (e.g. Byetta with Januvia) in combination
1. Raises cost, risk of Pancreatitis without significant benefit
2. (2012) Presc Lett 19(8): 45
Concurrent prandial Insulin (Bolus Insulin)
1. Basal insulin (e.g. Lantus) may be used
Medications that require rapid gastrointestinal absorption
1. Take at least one hour before Immediate release Lixisenatide (Adlyxin)