medwireNews: Lixisenatide is one of two (the other being liraglutide) daily injectable glucagon-like peptide (GLP)-1 receptor agonists available in Europe and the USA at the time of writing.
In this article, we provide an overview of the GetGoal series of clinical trials, which formed the basis of the medication’s approval, plus other relevant industry-sponsored (Sanofi) phase 3 trials, with links to the published results.
The ELIXA trial tested the cardiovascular safety profile of lixisenatide, and is covered in our Round-up of the GLP-1 receptor agonist CV outcome trials.
See also:
- A quick guide to the SURPASS and SURMOUNT trials (tirzepatide)
- A quick guide to the STEP trials (semaglutide for obesity)
- A quick guide to the PIONEER trials (oral semaglutide)
- A quick guide to the SUSTAIN trials (semaglutide)
- A quick guide to the AWARD trials (dulaglutide)
- A quick guide to the LEAD trials (liraglutide)
- A quick guide to the DURATION trials (exenatide)
The GetGoal series
GetGoal-Mono: Published
Trial population: People with type 2 diabetes treated with diet and exercise | Comparator treatment: Placebo |
As the name suggests, this trial tested lixisenatide in people who were medication-naïve. It is published in Diabetes Care.
Over 12 weeks of treatment, people taking lixisenatide 20 μg experienced an average 0.85% reduction in glycated hemoglobin (HbA1c) levels, compared with a 0.19% reduction in the placebo group, which was a significant difference favoring lixisenatide.
There was no difference for weight outcomes, however, with participants achieving around a 2 kg reduction regardless of treatment allocation.
GetGoal-M: Published
Trial population: People with type 2 diabetes taking metformin | Comparator treatment: Placebo |
Lixisenatide was given in either the morning or evening in this trial, and resulted in an average 0.8–0.9% reduction in HbA1c, which was significant versus the 0.4% decrease among people given placebo.
Again, there was no difference for weight outcomes, with all treatment groups achieving around a 2 kg reduction.
The trial is published in Diabetes Care.
GetGoal-X: Published
Trial population: People with type 2 diabetes taking metformin | Comparator treatment: Exenatide |
This trial, again published in Diabetes Care, showed that a daily injection of lixisenatide delivered statistically noninferior results to a twice-daily exenatide injection, although the numbers were slightly in favor of exenatide.
The average HbA1c reductions at week 24 were 0.79% with lixisenatide and 0.96% with exenatide and the corresponding weight reductions were 2.96 and 3.98 kg.
GetGoal-F1: Published
Trial population: People with type 2 diabetes taking metformin | Comparator treatments: Placebo |
This trial was designed in part to assess the effect of two different titration regimens on the tolerability of lixisenatide. As reported in Diabetic Medicine, one or two titration steps prior to starting the target dose were equally tolerable to the trial participants.
The average HbA1c decreases were 0.8–0.9% with lixisenatide versus 0.4% with placebo, and the corresponding weight reductions were 2.6–2.7 kg and 1.6 kg, with both differences significantly favoring lixisenatide.
GetGoal-S: Published
Trial population: People with type 2 diabetes taking metformin and a sulfonylurea | Comparator treatment: Placebo |
The GetGoal-S trial showed that lixisenatide treatment reduced HbA1c and bodyweight in people with poor glucose control on metformin plus a sulfonylurea.
As reported in the Journal of Diabetes and its Complications, the average HbA1c reductions at week 24 were 0.85% and 0.10% with lixisenatide and placebo, respectively. The corresponding weight reductions were 1.76 and 0.93 kg.
GetGoal-P: Published
Trial population: People with type 2 diabetes taking metformin and pioglitazone | Comparator treatment: Placebo |
This trial showed the glycemic and weight benefits of lixisenatide treatment in people already taking metformin and pioglitazone.
At week 24, the average HbA1c decrease was 0.90% with lixisenatide, which was significantly greater than the 0.34% reduction with placebo, and lixisenatide treatment resulted in an average 0.2 kg reduction in bodyweight compared with a 0.2 kg increase in the placebo group.
GetGoal-P is published in Diabetes, Obesity and Metabolism.
GetGoal-L: Published
Trial population: People with type 2 diabetes treated with basal insulin with/without metformin | Comparator treatment: Placebo |
This trial, reported in Diabetes Care, assessed the efficacy of lixisenatide in people already using basal insulin to control their blood sugar levels.
Lixisenatide reduced HbA1c by an average of 0.7% over 24 weeks of treatment, which was significantly greater than the average 0.4% reduction achieved in the placebo group. Bodyweight decreased by a corresponding 1.8 and 0.5 kg.
GetGoal-Duo 1: Published
Trial population: People with type 2 diabetes poorly controlled on oral antidiabetic medications | Comparator treatment: Placebo |
For this trial, the investigators enrolled participants with poor glucose control but not yet using injectable therapies. The participants were started on insulin glargine and those with persisting high glucose levels after a 12-week titration period (54% of all enrolled) were randomly assigned to receive additional lixisenatide or placebo.
In these people, 24 weeks of lixisenatide treatment resulted in an HbA1c reduction averaging 0.7%, which was significantly greater than the 0.4% decrease in the placebo group, making it an alternative to prandial insulin for this population.
Bodyweight increased by an average of 0.3 and 1.2 kg in the lixisenatide and placebo groups, respectively, which was also a significant difference. The findings are published in Diabetes Care.
GetGoal Duo-2: Published
Trial population: People with type 2 diabetes poorly controlled on oral antidiabetic medications | Comparator treatment: Insulin glulisine |
Building on the findings of GetGoal-Duo 1, this trial tested lixisenatide against a prandial insulin given one or three times daily in people on titrated basal insulin.
As reported in Diabetes Care, HbA1c declined by an average of 0.6% with lixisenatide, 0.6% with once-daily glulisine, and 0.8% with glulisine three times daily, making lixisenatide noninferior to the insulin. And bodyweight fell by an average of 0.6 kg in people taking lixisenatide, whereas it increased by 1.0–1.4 kg in those using the prandial insulin.
GetGoal-O: Published
Trial population: People with type 2 diabetes aged ≥70 years taking oral antidiabetic medications and/or insulin | Comparator treatment: Placebo |
This trial, also published in Diabetes Care, focused on use of lixisenatide in people aged 70 years or older and found similar efficacy to that in younger cohorts.
During 24 weeks of treatment, HbA1c levels fell by 0.57% on average in participants given lixisenatide versus a very slight increase of 0.06% in the placebo group. Bodyweight reduced by an average of 1.47 kg in the lixisenatide group compared with 0.16 kg with placebo.
Other industry-sponsored phase 3 trials
Efficacy in younger people with obesity
This trial (NCT00976937) compared the weight loss efficacy of lixisenatide with the dipeptidyl peptidase-4 inhibitor sitagliptin in people with type 2 diabetes and obesity younger than 50 years.
The findings have not been published in a journal but the results posted on clinicaltrials.gov indicate that lixisenatide was not statistically superior to sitagliptin for the primary endpoint at week 24. This was the percentage of participants who achieved HbA1c less than 7.0% (53 mmol/mol) and also lost at least 5% of their initial bodyweight, seen in 12.0% and 7.5% of the lixisenatide and sitagliptin groups, respectively.
The timing of lixisenatide injection
Another trial (NCT01517412) compared the efficacy of lixisenatide injections given at breakfast time or with the main meal of the day. The results published in the Journal of Diabetes and its Complications revealed no difference between the two strategies.
Trials in Japanese/Asian populations
GetGoal-Mono-Japan: Published
Trial population: Japanese people with type 2 diabetes not medication-treated except for sulfonylureas or α-glucosidase inhibitors | Comparator treatment: One-step vs two-step lixisenatide titration regimens |
The primary aim of this trial, published in the Journal of Diabetes and its Complications, was to compare the tolerability of titration schemes with one or two dose increments before the target dose. The results supported use of the two-step regimen in Japanese people.
The trial participants achieved average 0.74–0.99% HbA1c reductions and 0.43–1.08 kg weight reductions.
GetGoal-M-Asia: Published
Trial population: Asian people with type 2 diabetes on metformin with/without sulfonylurea | Comparator treatment: Placebo |
This trial tested the efficacy of lixisenatide in participants from China, Malaysia, Thailand, and Hong Kong.
During 24 weeks of treatment, HbA1c level declined by an average of 0.83% with lixisenatide treatment and 0.47% with placebo, which was a significant difference, and bodyweight by a respective 1.50 and 1.24 kg, which was not.
The results are published in Diabetes/Metabolism Research and Reviews.
GetGoal-L-Asia: Published
Trial population: Asian people with type 2 diabetes taking insulin with/without a sulfonylurea | Comparator treatment: Placebo |
Participants of this 24-week trial, published in Diabetes, Obesity and Metabolism, came from Japan, South Korea, Taiwan, and the Philippines.
HbA1c levels fell by an average of 0.77% among those taking lixisenatide but increased by 0.11% in the placebo group. Similarly, there was an average 0.38 kg decrease in bodyweight with lixisenatide versus a 0.06 kg increase with placebo, although this difference was not statistically significant.
GetGoal-L-C: Published
Trial population: People with type 2 diabetes taking insulin with/without metformin | Comparator treatment: Placebo |
Just over half the participants of this trial came from China, and the others from India, South Korea, and Russia.
As reported in Diabetes, Obesity and Metabolism, people taking lixisenatide achieved an average 0.62% reduction in HbA1c, which was significantly greater than the 0.11% reduction for those taking placebo.
The corresponding bodyweight reductions averaged 1.12 and 0.04 kg, with this difference also being statistically significant.
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