Can a non-insulin drug improve treatment results for patients with uncontrolled type 2 diabetes taking insulin?

This study examined if non-insulin drug lixisenatide (Lyxumia) boosted treatment results from insulin glargine (Lantus) in patients with uncontrolled type 2 diabetes (T2D). Patients who received lixisenatide and glargine had improved blood glucose control and no significant increase in side effects.

Uncontrolled diabetes means that blood glucose levels remain high, despite treatment. Uncontrolled T2D can lead to further complications and should be prevented or treated with different therapies. 

There are several types of treatments available for patients with T2D. These include insulin (including glargine) and other drugs such as GLP-1 receptor agonists (GLP-1RAs). GLP-1RAs increase the production and release of naturally made insulin by the body. Lixisenatide is a GLP-1RA drug. It is unclear if lixisenatide can improve results for patients with T2D taking insulin such as glargine.

502 patients with uncontrolled T2D were divided into two groups. 248 patients were given glargine and lixisenatide (GlarLixi group). 254 patients were given glargine (Glar group). Patients’ responses were measured for 26 weeks.

HbA1c, a measure of blood glucose levels over the previous 3 months, was significantly more reduced in patients receiving lixisenatide. In the GlarLixi group, HbA1c levels dropped from an average of 8.08% (64.8 mmol/mol) to an average of 6.66% (49.3 mmol/mol) after 26 weeks. In the Glar group, HbA1c levels dropped from 8.01% (64 mmol/mol) to 7.26% (55.8 mmol/mol). 

By 26 weeks, 71.5% of patients in the GlarLixi group had controlled HbA1c levels (below 7%). This was compared to 38.5% of patients in the Glar group.

Two hours after a meal, patients in the GlarLixi had a lower blood glucose level than the Glar group by 4.45 mmol/mol. Patients in the GlarLixi group gained less weight (0.26 kg) than the Glar group (1.33 kg).

Hypoglycemia is when blood glucose drops too low and can lead to other complications. During 26 weeks of treatment, 14.2% of the GlarLixi group and 12.3% of the Glar group developed hypoglycemia. 

62.7% of the GlarLixi group and 63.6% of the Glar group developed side effects. The most common side effects were infections (30.8% of GlarLixi and 35.2% of Glar) and side effects in the gut (26.2% of GlarLixi and 14.9% of Glar). 

The authors concluded that lixisenatide safely improved treatment results for patients receiving insulin glargine for uncontrolled T2D.

The manufacturer of lixisenatide, Sanofi, funded this study. This study was carried out in Japan so it may not reflect results seen in other populations. The Glar group was not given a placebo instead of lixisenatide so there may have been some bias in the results.