Concentrated Insulin Glargine, TOUJEO: Limited Use for Diabetes

TOUJEO is a concentrated form of the synthetic insulin known as insulin glargine. It contains 300 units per milliliter (U/mL) of insulin glargine and was approved by the Food and Drug Administration (FDA) in 2015 to treat diabetes mellitus.[1] In 2016, Public Citizen’s Health Research Group designated this form of insulin as Do Not Use for Seven Years because the drug was not a major breakthrough for treating diabetes (compared with older, less concentrated, once-daily formulations of insulin glargine containing 100 U/mL [LANTUS], which became available in biosimilar form [BASAGLAR] in 2016) and also because the long-term adverse effects of Toujeo were not yet known.[2]

As seven years have passed since Toujeo’s approval without new major safety concerns being identified, Public Citizen’s Health Research Group has now designated it as Limited Use — a treatment for diabetes that should be used only if treatment with less concentrated and cheaper forms of insulin have first been tried and found to be inadequate.

Toujeo versus other insulins

Insulin glargine remains the most commonly prescribed form of insulin in the U.S. Notably, Sanofi-Aventis developed both Lantus and Toujeo. In an effort to boost its market share, Sanofi-Aventis tried (but failed) to persuade the FDA to permit Toujeo to be labeled as a more effective and safer alternative to Lantus, which lost patent protection in 2016.[3] The FDA denied this request because evidence from four clinical trials only demonstrated that Toujeo was “non-inferior” to (no worse than) Lantus at reducing blood hemoglobin A1c levels (HbA1c, a measure of a patient’s long-term blood sugar control) following six months of treatment.[4] Moreover, subjects receiving Toujeo, on average, required higher doses of the drug than subjects receiving Lantus. In fact, FDA medical officers concluded that it may be less effective than Lantus in lowering blood sugar, particularly during the first few weeks of treatment.[5] Accordingly, since 2015, Toujeo’s product labeling has carried a warning about the risk of hyperglycemia (high blood sugar) during the first few weeks of treatment.[6],[7]

As of August 2022, the FDA-approved product labeling for Toujeo confirms that it is no better than Lantus as a method to control blood sugar in patients with diabetes based on data from several randomized clinical trials in adults, older adults and children.[8]

A 2020 observational study of type 2 diabetes patients in Japan offers some of the most recent published information regarding the safety and effectiveness of Toujeo compared with other insulin products. These researchers followed 1,227 patients new to insulin and another 3,394 patients who switched to Toujeo from another insulin form. They found that HbA1C levels on average decreased from 9.8% to 7.8% after 12 months of Toujeo use in patients not previously treated with insulin but only decreased from 8.0% to 7.8% on average in those who switched from another insulin.[9]

Furthermore, symptomatic hypoglycemia (low blood sugar) was similar in both patient groups, occurring in 3% of the patients not previously treated with an insulin and 4% of the insulin switchers.

Risks of Toujeo

Severe hypoglycemia, a serious safety issue for all insulin products, can lead to loss of consciousness, seizures or even death. Preapproval clinical trials data suggested that Toujeo may increase the risk of severe hypoglycemia in some diabetic patients. For example, the incidence of severe hypoglycemia that occurs at night during sleep was slightly greater in patients with type 1 diabetes treated with Toujeo (2.2%) than in those using Lantus (1.8%).[10] Severe daytime hypoglycemia occurred more frequently in type 2 diabetes patients using Toujeo (4%) than in those using Lantus (2.5%).[11] The August 2022 labeling reports that 5% to 7% of those using Toujeo multiple times per day experienced severe hypoglycemia (requiring the assistance of another person to resuscitate) over a 26-week trial period.[12]

Toujeo also is associated with an increased risk of severe, life-threatening allergic reactions. In clinical trials, subjects with type 1 diabetes were more likely to experience an allergic reaction using Toujeo (6.6%) than using Lantus (4.6%). 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 treated with Lantus.[13] Respiratory failure was also the cause of death in one patient treated with Toujeo during the clinical testing.

The August 2022 product labeling for Toujeo further notes that the most common adverse reactions in adults with diabetes were nasopharyngitis (head colds) and upper respiratory tract infections, which occurred in 6% to 13% of the patients.[14]

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 an increased risk of fluid retention, which can cause or worsen heart failure, when the drug is used with another class of diabetes drugs known as thiazolidinediones or glitazones (for example, pioglitazone [ACTOS]), and hypokalemia (low potassium blood levels), which can lead to arrhythmias (abnormal heart rhythms) or death. Lipodystrophy (depressions in or thickening of the skin) at the injection site may occur and can change insulin absorption if that affected site is used again.[15]

What You Can Do

We recommend that you only use Toujeo after first trying other insulins, including Lantus, Basaglar and NPH insulin (HUMULIN, NOVOLIN).

Contact your doctor immediately if you experience any of the following symptoms while using Toujeo:[16]
 

• rash, hives or itching all over your body
• wheezing or difficulty breathing
• symptoms of hypoglycemia, including rapid heartbeat, shaking, sweating, nervousness or anxiety, confusion and dizziness
• swelling of the eyes, face, lips, tongue or throat
• difficulty swallowing
• hoarseness
• muscle cramps

You should also contact your doctor if you experience any of the following symptoms while using Toujeo that are severe or do not go away:[17]

• redness, swelling, pain or itching at the injection site
• changes in the feel of your skin, skin thickening (fat build-up) or a little depression in the skin (fat breakdown)
• fever, cough, sore throat or other signs of infection

Whenever you are on insulin, it is important to practice healthy exercise and diet, which are often instrumental in controlling blood sugar levels.
 

References

[1] Sanofi-Aventis. Label: insulin glargine (TOUJEO U-300), August 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/206538s016lbl.pdf. Accessed February 7, 2023.

[2] Worst Pills Best Pills News. Insulin Glargine (TOUJEO): Do Not Use for Seven Years. November 2016. https://www.worstpills.org/newsletters/view/1068. Accessed February 7, 2023.

[3] 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 February 7, 2023.

[4] Worst Pills Best Pills News. Insulin Glargine (TOUJEO): Do Not Use for Seven Year. November 2016. https://www.worstpills.org/newsletters/view/1068. Accessed February 7, 2023.

[5] 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 February 7, 2023.

[6] Worst Pills Best Pills News. Insulin Glargine (TOUJEO): Do Not Use for Seven Year. November 2016. https://www.worstpills.org/newsletters/view/1068. Accessed February 7, 2023.

[7] Sanofi-Aventis. Label: insulin glargine (TOUJEO U-300), August 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/206538s016lbl.pdf. Accessed February 7, 2023.

[8] Ibid.

[9] Odawara M, Matsuhisa M, Hirose T et al. Effectiveness and safety of insulin glargine 300 unit/mL in Japanese type 2 diabetes mellitus patients: a 12-month post-marketing surveillance study (X-STAR study). Expert Opin Pharmacother. 2020;21(14):1771-1780.

[10] 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 February 7, 2023.

[11] Ibid.

[12] Sanofi-Aventis. Label: insulin glargine (TOUJEO U-300), August 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/206538s016lbl.pdf. Accessed January 24, 2023.

[13] 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 February 7, 2023.

[14] Sanofi-Aventis. Label: insulin glargine (TOUJEO U-300), August 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/206538s016lbl.pdf. Accessed February 7, 2023.

[15] Ibid.

[16] MedlinePlus. Insulin Glargine (rDNA origin) Injection. August 15, 2022. https://medlineplus.gov/druginfo/meds/a600027.html. Accessed February 14, 2023.

[17] Ibid.