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Diabetes drug combo tied to favourable outcomes

Audrey Abella
18 Jan 2018

A titratable, fixed-ratio combination of insulin glargine 100 U/mL and the GLP-1* receptor agonist lixisenatide was associated with favourable glycaemic and gastrointestinal outcomes in patients with type 2 diabetes (T2D), according to several studies presented at IDF 2017.

 

Greater HbA1c reduction

Data from the LixiLan-L** trial demonstrated the efficacy of the insulin glargine-lixisenatide combination vs insulin glargine alone among patients with T2D uncontrolled on basal insulin. Participants were randomized to receive combination therapy (n=366) or continue with insulin glargine alone (n=365) for 30 weeks. [IDF 2017, abstract P-0392]

Among those who reached the maximum dose of 60 U/day (27 percent and 30.7 percent in the combination and insulin glargine arms, respectively), more participants from the combination arm achieved the glycaemic goal of HbA1c ≤7 percent (43 percent vs 24 percent). Combination therapy also resulted in greater mean HbA1c reduction (-1 percent vs -0.5 percent), greater postprandial glucose (PPG) reduction (-90.2 vs -23.8), and less weight gain (-0.2 vs 1.2) at week 30 vs insulin glargine alone.

 

Potential weight loss benefit

Findings from a network meta-analysis support these findings and favour insulin glargine/lixisenatide over premix insulin in terms of HbA1c reduction, given the greater relative mean difference (RMD) in HbA1c reduction (RMD, 0.34, 95 percent credible interval [CrI], -0.32 to 1.00), and decreased likelihood of achieving the ≤7 percent HbA1c glycaemic target associated with premix insulin (odds ratio, 0.33, 95 percent CrI, 0.027–4.0). [IDF 2017, abstract P-0534]

Additionally, an increase in body weight was observed with premix insulin vs insulin glargine/lixisenatide (RMD, 2.5 kg, 95 percent CrI, 0.72–4.4].

Although the results were nonsignificant, the researchers indicated that the insulin glargine-lixisenatide combination “allows comparable control over HbA1c, and a greater advantage for preventing weight gain in comparison with premix-based insulin therapy.”

They added that these results yield an efficacy profile for insulin glargine/lixisenatide. “[Our findings] provide further information [on] the benefit-risk profile for treatment intensification with [insulin glargine/lixisenatide] in patients not reaching glycaemic targets with basal insulin.”

 

Favourable safety profile

Results from a post hoc analysis comparing data from the LixiLan-L and LixiLan-O*** trials demonstrated reduced rates of gastrointestinal adverse events (GI AEs) such as nausea, vomiting, and diarrhoea (≤10 percent vs ≤24 percent). Discontinuation rates due to GI AEs (≤1 percent vs ≤2.6 percent) were also substantially lower with the insulin glargine-lixisenatide combination (LixiLan-L) vs lixisenatide alone (LixiLan-O). [IDF 2017, abstract P-0391]

There was a lower incidence of nausea, vomiting, or diarrhoea within the first 60 days of treatment initiation (9.6 percent vs 27.5 percent), and fewer patients with onset of GI AEs from day 60 to study end (4.1 percent vs 6.9 percent) among insulin glargine/lixisenatide vs lixisenatide recipients.

According to the researchers, the lower incidence and severity of GI AEs among insulin glargine/lixisenatide recipients could be related to the titration protocol for insulin glargine/lixisenatide, resulting in gradual small increases in the lixisenatide dose paralleling the insulin glargine titration according to fasting plasma glucose (FPG) targets. “[This] may mitigate the risk of GI AEs seen when lixisenatide is administered separately as a fixed dose with dose-doubling after 2 weeks (10-20 μg),” they added.

Most GI AEs associated with insulin glargine/lixisenatide were mild (53–78 percent) to moderate (22–45 percent), were predominantly transient, and mostly occurred during the initial 8-week period, subsiding over time.

Overall, these evaluations demonstrate the efficacy of the insulin glargine-lixisenatide combination over basal insulin through their complementary mechanisms of action targeting FPG (insulin glargine) and PPG (lixisenatide). [Diabetes Obes Metab 2013;15:485-502; Diabetes Care 2013;36:2497-2503]

 

 

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Most Read Articles
01 Oct 2017
Antidepressants may be effective for treating depression in patients with schizophrenia, according to a meta-analysis that underscores qualifying conclusions based on the small number of low- or moderate-quality studies.
Jairia Dela Cruz, 09 Jan 2017
The sulfonylurea glimepiride may pose an increased risk of hypoglycaemia in a subgroup of elderly type 2 diabetes (T2D) patients with lower β-cell function when added to a metformin regimen, according to a post-hoc analysis of data from the GENERATION* trial.
10 Apr 2018
Antiviral treatment for colonic cytomegalovirus (CMV) infection significantly improves short- and long-term surgery-free survival in patients with ulcerative colitis (UC), according to the results of a small-scale study.
Audrey Abella, 03 Oct 2017
Once-monthly and once-quarterly administration of paliperidone palmitate had similar efficacy in terms of relapse prevention for schizophrenia in an East Asian population, according to a subgroup analysis.