Patients with poorly controlled type 2 diabetes assigned the GLP-1 receptor agonist lixisenatide experienced reductions in HbA1c, fasting plasma glucose and body weight over 26 weeks, even in the setting of markedly diminished beta-cell function, according to a post hoc analysis of the GetGoal trials.
Riccardo C. Bonadonna, MD, associate professor of medicine at the university of Parma, Italy, and colleagues analyzed data from 546 patients with poorly controlled type 2 diabetes participating in three randomized, double blind, placebo-controlled GetGoal trials evaluating the safety and efficacy of lixisenatide (Lyxumia, Sanofi) vs. oral antidiabetes therapies over 26 weeks (n = 273 for each cohort). In this analysis, all included patients were randomly assigned to lixisenatide and had baseline and endpoint measurements for HbA1c and homeostasis model assessment of beta-cell function (HOMA-beta index). Participants were stratified by baseline HOMA-beta index level by using propensity scoring: high (above the median level of 28.49%); median and low (below the median value). Key endpoints included mean change from baseline to endpoint in HbA1c, postprandial plasma glucose, glucose excursion, fasting plasma glucose, body weight, BMI and HOMA-beta index, as well as the proportion of patients reaching an HbA1c target of 7% or less, an FPG target of 6.11 mmol/L or less and switching HOMA-beta index group between baseline and endpoint.
Participants in both the high and low HOMA-beta index groups saw similar reductions in HbA1c during treatment (mean, –0.94% and –0.85%, respectively); a similar proportion of patients in the high and low HOMA-beta index groups reached an HbA1c of 7% or lower over 26 weeks (45.79% and 43.59%, respectively). Both the high and low HOMA-beta groups also experienced similar reductions in postprandial plasma glucose (P = .7511) and glucose excursion (P = .9592), despite a difference in baseline postprandial plasma glucose that was not accounted for in propensity scoring. Both groups also experienced similar reductions in FPG, although a greater proportion of patients in the high HOMA-beta group reached the FPG target of 6.11 mmol/L or less vs. the low group (15.75% vs. 9.89%). The low HOMA-beta group experienced greater weight loss than the high group during treatment (–2.06 kg vs. –1.13 kg; P = .0006).
Researchers observed no between-group differences in achieving the composite endpoint of HbA1c 7% or less with no symptomatic hypoglycemia, HbA1c 7% with no weight gain and HbA1c 7% with no weight gain and no symptomatic hypoglycemia.
“Our findings indicate that treatment with once-daily lixisenatide is effective in reducing hyperglycemia, is well-tolerated and associated with weight loss, even when [beta]-cell function is low, and highlights the importance of the non-[beta]-cell-mediated actions of lixisenatide in improving glycemic control,” the researchers wrote. – by Regina Schaffer
Disclosures: Sanofi sponsored this study. Bonadonna reports serving on advisory panels for Amgen, Eli Lilly, Merck and Sanofi, and has receiving speaking fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Sanofi. Please see the full study for the other authors’ relevant financial disclosures.