Switch to Combined GLP1 Receptor Agonist Lixisenatide with Basal Insulin Glargine in Poorly Controlled T2DM Patients with Premixed Insulin Therapy: A Clinical Observation and Pilot Study in Nine Patients.

INTRODUCTION: To prove the feasibility and safety of a conversion to once-daily injected GLP1 agonist (lixisenatide) and long-acting basal insulin analogue (glargine) in patients with T2DM and poorly controlled glycemia previously treated with multiple injections of premixed insulins (iPremix) in an outpatient setting. METHODS: Nine patients with T2DM currently receiving iPremix formulations and poor glycemic control were switched to once-daily injected lixisenatide (Lixi) and basal insulin analogue glargine (iGlar) for a 12-week period. Efficacy was defined as A1c reduction of at least 0.4% and weight loss of 0.5 kg or higher. RESULTS: Five of nine patients achieved A1c reductions of 0.4% (4 mmol/mol) or higher and six of nine patients a weight loss of 0.5 kg or higher. A mean A1C reduction of 0.5% ± 0.5% (6 mmol/mol) and mean weight loss of -1.4 ± 3.6 kg were observed in all patients. Total daily insulin dose after 12 weeks declined from 56 ± 26 IU with iPremix formulations to 47 ± 17 IU in patients taking combined iGlar and Lixi. Corrections with fast acting insulin glulisine (iGlu) were necessary in two patients on a regular basis and in four patients on an irregular basis (2.3 IU mean total daily dose). Two patients did not need additional iGlu. Postprandial glucose profiles were lower in the combined group compared with iPremix throughout the day, which resolved in the afternoon. No metabolic derangements occurred. Mild hypoglycemia and gastrointestinal symptoms were the most often reported adverse events affecting three patients. CONCLUSION: The conversion to once-daily injected GLP1 agonist Lixi and basal iGlar could safely be performed in an outpatient setting and was associated with better postprandial glycemic control throughout the day, except dinner, compared to iPremix. CLINICAL TRIAL REGISTRATION: EU clinical trials register EudraCT number 2013-005334-37 and ClinicalTrials.gov NCT02168491. FUNDING: Sponsored by the Medical University of Vienna and in part supported by Sanofi-Aventis.