Insulin Glargine (TOUJEO): Do Not Use for Seven Years

TOUJEO (insulin glargine) is a newer, long-acting, once-daily insulin approved by the Food and Drug Administration (FDA) in February 2015 for the treatment of Type 1 and Type 2 diabetes in adults.[1] Long-acting insulins take longer to work than short-acting or “mealtime” insulins, but they can last for more than 12 hours, making them beneficial for controlling blood sugar levels throughout the day.

Public Citizen’s Health Research Group has designated TOUJEO as Do Not Use for Seven Years, because the drug does not represent a major breakthrough for treating diabetes. Importantly, it has not been shown to be more effective or safer than an older, less concentrated oncedaily formulation of insulin glargine (LANTUS).[2] The long-term adverse effects of TOUJEO in patients with Type 1 or Type 2 diabetes are also not known.[3],[4]

LANTUS and TOUJEO are both manufactured by Sanofi-Aventis. LANTUS, the most widely prescribed insulin in the U.S., was approved by the FDA in 2000, and its patent will expire in late 2016. In fact, the FDA has already approved the first generic equivalent to LANTUS (known as a “biosimilar”). The generic form, BASAGLAR, will be available to patients beginning in December 2016.[5],[6]

In an effort to maintain its market share, Sanofi-Aventis has tried to persuade the FDA to approve labeling for TOUJEO indicating that the drug is a more effective and safer alternative to LANTUS in diabetic patients.[7] Evidence from four clinical trials funded by Sanofi-Aventis, however, only demonstrated TOUJEO was “non-inferior” to (or no worse than) LANTUS at reducing a blood chemical called hemoglobin A1c (a measure of blood sugar control following six months of treatment.[8] Moreover, subjects receiving TOUJEO in the clinical trials on average required higher doses of the drug than subjects receiving LANTUS. The FDA therefore did not allow the company to market TOUJEO as a substitute for LANTUS,[9] or to state in the product’s labeling that it was safer or more effective than LANTUS.[10]

FDA medical officers carefully reviewing the clinical trial data for TOUJEO prior to its approval concluded that TOUJEO may actually be less effective than LANTUS in lowering blood sugar, particularly during the first few weeks of treatment.[11] In fact, TOUJEO’s label warns about the risk of hyperglycemia (high blood sugar levels) during the first few weeks of treatment in diabetic patients who start TOUJEO.[12]

Hypoglycemia risk

Despite efforts by the manufacturer to prove to the FDA that TOUJEO carries a lower risk of hypoglycemia (low blood sugar) than LANTUS,[13] the FDA concluded from the clinical trial data that TOUJEO is no safer than LANTUS in this regard.[14] In fact, the FDA-approved label for TOUJEO claims there is no difference in the incidence of hypoglycemia between the two glargine insulin products.[15]

Severe hypoglycemia, a serious safety concern associated with all insulin products, can lead to loss of consciousness, seizures or even death. Pre-approval clinical trial data suggest that TOUJEO may increase the risk for severe hypoglycemia in some diabetic patients. For example, the incidence of severe nocturnal hypoglycemia (hypoglycemia that occurs at night, when a patient is sleeping) was slightly greater in patients with Type 1 diabetes treated with TOUJEO (2.2 percent) than in those using LANTUS (1.8 percent).[16] Severe daytime hypoglycemia occurred more frequently in Type 2 diabetic patients using TOUJEO (4.0 percent) than in those using LANTUS (2.5 percent).[17]

TOUJEO is also associated with an increased risk of severe, life-threatening allergic reactions. In the clinical trials, subjects with Type 1 diabetes were more likely to experience an allergic reaction using TOUJEO (6.6 percent) than using LANTUS (4.6 percent). In fact, during the trials, three cases of serious allergic reactions, including acute respiratory failure (sudden difficulty breathing), were reported in TOUJEO-treated subjects and none in those using LANTUS.[18] Respiratory failure was also the cause of death in one patient treated with TOUJEO during clinical testing.

Injection site reactions, particularly bruising and pain, also occurred more frequently in TOUJEO-treated Type 1 diabetes patients. Product labeling for TOUJEO, like that for LANTUS and most other insulin products, warns about increased risk of fluid retention, which can cause or worsen heart failure, when used with another class of diabetes drugs known as glitazones (for example, pioglitazone [ACTOS]), and hypokalemia (low potassium blood levels), which can lead to arrhythmias (abnormal heart rhythms) or death.

What You Can Do

We recommend that you do not use TOUJEO for seven years after its approval (until February 2022) because there is no evidence that it is more effective or safer than LANTUS in treating Type 1 or Type 2 diabetes. Additionally, the long-term adverse effects of TOUJEO in patients with diabetes are still not known.[19],[20]

If you need insulin, you should avoid starting TOUJEO if you are not currently taking it. You should instead use one of the older long-acting insulin for Type 1 or Type 2 diabetes with a better established safety profile. These include NPH insulin (HUMULIN, NOVOLIN), which is a longacting form of human insulin, and LANTUS.

Along with taking drugs, you should practice healthy exercise and diet, which are often instrumental in controlling blood sugar levels.

For more advice on treatments for diabetes, see the May 2014 issue of Worst Pills, Best Pills News or WorstPills.org.

References

[1] Sanofi-Aventis. Label: insulin glargine injection (TOUJEO). September 2015. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9561d96-124d-48ca-982f-0aa1575bff36. Accessed September 16, 2016.

[2] Insulin glargine (Lantus), a new long-acting insulin. Med Lett Drugs Ther. 2001;43: 65-66.

[3] Riddle MC, Bolli GB, Ziemen M, et al. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin: Glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 1). Diabetes Care. 2014;37(10):2755-2762.

[4] Sanofi-Aventis. Label: insulin glargine injection (TOUJEO). May 2015. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9561d96-124d-48ca-982f-0aa1575bff36. Accessed August 24, 2016.

[5] Eli Lilly and Co., Boeringer Ingelheim. Insulin glargine injection (BASAGLAR). https://www.basaglar.com/#. Accessed August 24, 2016.

[6] Guettier JM. Letter to Eli Lilly and Company. December 16, 2015. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/205692Orig1s000ltr.pdf. Accessed August 24, 2016.

[7] Yanoff L. Cross Disciplinary Team Leader Review for TOUJEO (insulin glargine) NDA 206538. February 3, 2015. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206538Orig1s000CrossR.pdf. Accessed August 24, 2016.

[8] Sanofi-Aventis. Label: insulin glargine injection (TOUJEO) May 2015. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9561d96-124d-48ca-982f-0aa1575bff36. Accessed August 24, 2016.

[9] Yanoff L. Cross Disciplinary Team Leader Review for TOUJEO (insulin glargine) NDA 206538. February 3, 2015. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206538Orig1s000CrossR.pdf. Accessed August 24, 2016.

[10] Sanofi-Aventis. Label: insulin glargine injection (TOUJEO). September 2015. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9561d96-124d-48ca-982f-0aa1575bff36. Accessed September 16, 2016.

[11] Condarco T. Medical Review for TOUJEO (insulin glargine) NDA 206538. January 21, 2015. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206538Orig1s000MedR.pdf. Accessed August 24, 2016.

[12] Sanofi-Aventis. Label: insulin glargine injection (TOUJEO) May 2015. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9561d96-124d-48ca-982f-0aa1575bff36. Accessed August 24, 2016.

[13] Guittier JM. Summary Review for TOUJEO (insulin glargine) NDA 206538. February 25, 2015. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206538Orig1s000SumR.pdf. Accessed August 24, 2016.

[14] Yanoff L. Cross Disciplinary Team Leader Review for TOUJEO (insulin glargine) NDA 206538. February 3, 2015. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206538Orig1s000CrossR.pdf. Accessed August 24, 2016.

[15] Sanofi-Aventis. Label: insulin glargine injection (TOUJEO) May 2015. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9561d96-124d-48ca-982f-0aa1575bff36. Accessed August 24, 2016.

[16] Condarco T. Medical Review for TOUJEO (insulin glargine) NDA 206538. January 21, 2015. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206538Orig1s000MedR.pdf. Accessed August 24, 2016.

[17] Ibid.

[18] Condarco T. Medical Review for TOUJEO (insulin glargine) NDA 206538. January 21, 2015. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206538Orig1s000MedR.pdf. Accessed August 24, 2016.

[19] Riddle MC, Bolli GB, Ziemen M, Muehlen-Bartmer I, Bizet F, Home PD; EDITION 1 Study Investigators. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 1). Diabetes Care. 2014;37(10):2755-2762.

[20] Sanofi-Aventis. Label: insulin glargine injection (TOUJEO). May 2015. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9561d96-124d-48ca-982f-0aa1575bff36. Accessed August 24, 2016.