Lixisenatide for Diabetes: What Pharmacists Should Know

MARCH 07, 2017
An estimated 29.1 million individuals in the United States have diabetes with another 86 million adults having pre-diabetes. Despite the introduction of several new classes of antidiabetic medications over the recent years, complications of the disease remain high.1
 
In July 2016, the FDA approved Adlyxin (lixisenatide) to improve glycemic control in adults with type 2 diabetes mellitus. Four months later, the FDA approved Soliqua, a fixed-ratio combination of lixisenatide and insulin glargine for patients with type 2 diabetes who are inadequately controlled on basal insulin (<60 units) or lixisenatide alone. 
 
This article will highlight several key therapeutics areas with lixisenatide that every pharmacist should know.
 
History
Lixisenatide (brand name Lyxumia), has been available since 2013 in many other countries. It is now the fifth GLP-1 receptor agonist to be approved in the United States.
 
Soliqua is 1 of 2 GLP-1 receptor agonist/basal insulin combinations to be FDA approved. Xultophy, a fixed-dose combination of insulin degludec and liraglutide, was approved on the same day as Soliqua. Xultophy is not expected to be launched into the market until May 2017, while Soliqua was introduced in January 2017.2
 
Indication
Both Adlyxin and Soliqua 100/33 are FDA-approved as adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Soliqua 100/33 is indicated specifically in those inadequately controlled on basal insulin (less than 60 units daily) or lixisenatide.3,4
 
Limitations of Use
Both products have not been studied in patients with a history of chronic or unexplained pancreatitis and therefore other antidiabetic therapies should be considered. Additionally, neither is recommended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis and should be avoided in patients with gastroparesis. Neither product has been studied in combination with short acting insulin.
 
Mechanism of Action
Lixisenatide is a GLP-1 receptor agonist that works by increasing glucose-dependent insulin release, decreasing glucagon secretion, and slowing gastric emptying.
 
Insulin glargine works through regulation of glucose metabolism. Specifically, insulin lowers blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production.
 
Formulation, Storage
Adlyxin is formulated as a 3 mL prefilled, single-patient use pen. It comes as a starter pack for treatment initiation and a maintenance pack. The starter pack contains 1 green pen containing 50 mcg/mL of lixisenatide (delivers 14 doses of 10 mcg), and 1 burgundy pen containing 100 mcg/mL (delivers 14 doses of 20 mcg). The maintenance pack contains 2 burgundy pens in the same strength.
 
Soliqua is formulated as a 3 mL prefilled, SoloStar pen. Each pen contains 100 units/mL of insulin glargine and 33 mcg/mL of lixisenatide. The pen delivers from 15 units to 60 units with each injection. It is available as a package of 5 pens.
 
Both products should be stored in the refrigerator prior to first use. Subsequently, they are recommended to be kept at room temperature. Each pen should be discarded 14 days after first use.
 
Dosing
Adlyxin is initiated at 10 mcg once daily for 14 days. On day 15, the dose is increased to 20 mcg once daily.
 
Prior to starting Soliqua 100/33, all basal insulin and GLP-1 agonist therapy should be stopped. In patients inadequately controlled on less than 30 units of basal insulin or on lixisenatide, the starting dosage is 15 units given subcutaneously once daily. In patients inadequately controlled on 30 to 60 units of basal insulin, the starting dosage is 30 units. The maximum recommended dosage is 60 units.
 
Both are recommended to be administered once daily within one hour before the first meal of the day. Preferred injection sites include subcutaneously in thigh, upper arm, or abdomen.
 
Efficacy
Lixisenatide monotherapy was studied in a 12-week, double-blind study with 241 type 2 patients with diabetes. Compared to placebo, lixisenatide resulted in statistically significant reductions in HbA1c from baseline at week 12. No differences were seen in weight loss.
 
Lixisenatide as add-on therapy to metformin, a sulfonylurea, pioglitazone, or insulin was studied in several trials and was found to lower HbA1c and reduce weight.  In one study, patients inadequately controlled on metformin, the addition lixisenatide was noninferior to the addition of exenatide in reducing HbA1C, but exenatide caused more weight loss. In a separate study, lixisenatide was found to be less effective than liraglutide in reducing A1C, while weight loss was similar with both drugs.
 
The efficacy of Soliqua 100/33 was assessed in combination with insulin glargine was assessed in a randomized 30-week, open-label trial in 736 diabetics inadequately controlled on basal insulin and one or two oral antidiabetic drugs. At week 30, there was a statistically significant reduction in HbA1c with the combination group compared to insulin glargine alone. Mean body weight decreased by 0.7 kg with the combination and increased by 0.7 kg with insulin glargine alone.2-5
 
Safety
The most common adverse reactions associated with lixisenatide during clinical trials were hypoglycemia, allergic reactions, nausea, nasopharyngitis, upper respiratory tract infection, and headache.
 
Drug Interactions
Adrenergic drugs, such as beta-blockers, clonidine, and reserpine, may mask signs and symptoms of hypoglycemia. Additionally, lixisenatide slows gastric emptying and therefore may decrease the rate and extent of absorption of oral medications. It is recommended that oral contraceptives and antibiotics be taken at least 1 hour prior to or 11 hours after these medications.
 
Counseling Points
Instruct patients receiving the Adlyxin starter pack that the green pen, which containers the lower strength, should be used for the full 14 days, before using the burgundy, or maintenance pen.
 
Pen needles are not included with either product. Patients should always use a new needle for each injection to prevent contamination or possible needle blockage.
 
If a patient misses a dose, skip the dose and continue as prescribed on the next day. Patients should never administer 2 doses on the same day or increase the dose to make up a missed dose. This applies to Soliqua 100/33 only. Guidance for missed doses is different for Adlyxin. Per Adlyxin PI, "If a dose is missed, administer Adlyxin within one hour prior to the next meal." 
 
Sanofi has a savings co-pay card for Soliqua 100/33 through their website. If eligible, patients can pay as little as $0 for 12 months. Additionally, the manufacturer offers a coaching program where interested patients can sign up for one-on-one patient support from a registered nurse, plus receive customized info and tools at no cost. There is also a savings program available for Adlyxin. See www.Adlyxin.com for more details. 
 
Product Comparison
Drug Formulations Dosing frequency Cost*
Soliqua 100/33 SoloStar pen QD $152.40
Adlyxin Prefilled pen QD $334.32
Xultophy Prefilled pen QD Not currently available
Insulin glargine (Lantus) Vial or SoloStar pen QD $89.46
Insulin glargine (Basaglar) KwikPen QD $76.04
 
*Cost based on average wholesale price (AWP) for one 3mL pen, per Lexi-Drugs. Cost to the patient will vary based on a patient’s insurance coverage.6
 
Guidelines
The American Diabetes Association’s 2017 Standards of Medical Care in Diabetes recommend GLP-1 agonists as a possible component of dual of triple therapy, in combination with metformin. Basal insulin is typically recommended in those with an HbA1c over 9, or in patients unable to achieve an HbA1c goal with two or three oral agents.
 
The guidelines don’t make specific recommendations for Soliqua, but note that basal insulin plus GLP-1 receptor agonists are associated with less hypoglycemia and weight loss instead of weight gain but may be less tolerable and have a greater cost.7
 
Conclusion
Lixisenatide provides patients with another injectable option to control their diabetes. Although Adlyxin is likely to have a limited role due to other GLP-1 receptor agonists on the market, Soliqua may be useful in those who are inadequately controlled on basal insulin alone.
 
References:
  1. Gregg E, Li Y, Wang J, et al. Changes in Diabetes-Related Complications in the United States, 1990–2010. N Engl J Med. 2014;370:1514-1523.
  2. Helfand C. Sanofi beats Novo to launch with diabetes combo Soliqua, kicking off the market-share grab. FiercePharma. Jan 6 2017. Available at: www.fiercepharma.com/marketing/sanofi-beats-novo-to-launch-diabetes-combo-soliqua-kicking-off-market-share-grab
  3. Adlyxin [Prescribing Information]. Sanofi. Bridgewater, New Jersey. July 2016.
  4. Soliqua [Prescribing Information]. Sanofi. Bridgewater, New Jersey. November 2016.
  5. Lixisenatide for Type 2 Diabetes. Med Lett Drugs Ther. 2017;59(1513):19-21
  6. Lexicomp Online®, Lexi-Drugs®, Hudson, Ohio: Lexi-Comp, Inc.; March 1, 2017.
  7. American Diabetes Association. Standards of Medical Care in Diabetes 2017. Diabet Care. 2017; 4040 (Suppl 1): 1-132.


Timothy O'Shea, PharmD
Timothy O'Shea, PharmD
Timothy O'Shea, PharmD, is a Clinical Pharmacist working at a large health insurance plan on the east coast. Additionally he works per diem at a retail pharmacy chain. He graduated from MCPHS University - Boston in 2015 and subsequently completed a PGY-1 Managed Care Pharmacy Residency. His professional interests include pharmacy legislation and managed care pharmacy. He can be followed on Twitter at @toshea125.
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