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Lixisenatide Treatment for Older Patients with Type 2 Diabetes Mellitus Uncontrolled on Oral Antidiabetics: Meta-Analysis of Five Randomized Controlled Trials

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Abstract

Aim

Evaluate the efficacy and safety of lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist, in older patients with type 2 diabetes mellitus (T2DM) insufficiently controlled on oral antidiabetics (OADs).

Methods

A meta-analysis was conducted on data from older patients (≥65 years) from five of the GetGoal trials, in which patients with T2DM were treated with lixisenatide 20 µg once daily or placebo, as an add-on to OADs. The primary endpoint in all trials was change from baseline at week 24 in glycated hemoglobin (HbA1c). Other endpoints included changes in post-prandial plasma glucose (PPG), fasting plasma glucose (FPG) and weight. Composite and safety endpoints were also analyzed.

Results

A total of 501 patients aged ≥65 years were included in this meta-analysis: 304 received lixisenatide plus OADs and 197 received placebo as add-on to OADs. Lixisenatide as an add-on to OADs significantly reduced HbA1c, PPG, FPG and weight, with placebo-corrected treatment effects at week 24 of −0.54% (p < 0.0001), −126 mg/dL (p < 0.0001), −13 mg/dL (p = 0.0005) and −0.90 kg (p = 0.0021), respectively. Patients receiving lixisenatide plus OADs were significantly more likely to achieve composite (HbA1c levels <7%, HbA1c levels <7% and no symptomatic hypoglycemia, and HbA1c levels <7%, no weight gain and no symptomatic hypoglycemia) and safety endpoints than those receiving placebo plus OADs. Symptomatic hypoglycemia was experienced by 8.55% and 3.55% of patients in the lixisenatide plus OADs and placebo plus OADs groups, respectively (p = 0.0276), although no serious hypoglycemic episodes were reported.

Conclusions

Lixisenatide plus OADs improved glycemic control in older patients inadequately controlled on OADs compared with placebo plus OADs. Lixisenatide is well tailored to the pathophysiology of T2DM in older patients.

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Acknowledgments

Sponsorship and article processing charges for this study were funded by Sanfoi SA, Paris, France. Medical writing assistance was provided by Sarah Barnes, PhD, of Caudex Medical and was funded by Sanofi. All named authors meet the ICMJE criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.

Conflict of interest

Markolf Hanefeld has received speaker honoraria from Takeda, GlaxoSmithKline (GSK), Roche, Bayer, Lilly and Sanofi-Aventis, and advisory board honoraria from Sanofi-Aventis, Takeda, Bristol-Myers Squibb (BMS) and GSK. M.H. has no conflicts to declare associated with this manuscript. Rachele Berria is an employee of Sanofi-Aventis. Jay Lin is an employee of Novosys Health, which received funding for the study from Sanofi. Ronnie Aronson has received research support and/or consulting honoraria from Sanofi-Aventis, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi and Takeda. Patrice Darmon has received speaker and/or consulting honoraria from Sanofi, Eli Lilly, Novo Nordisk, Novartis, Merck Sharp & Dohme (MSD), Boehringer Ingelheim, BMS and Takeda. Marc Evans has received research awards and/or consulting honoraria from Novo Nordisk, Sanofi-Aventis, MSD, Takeda and Novartis. Luc Van Gaal is/has been a member of Advisory Boards and Speaker Bureaus of Astra Zeneca/BMS, Boehringer Ingelheim, Eli Lilly, Janssen Johnson & Johnson, MSD, Novartis, Novo Nordisk and Sanofi (period 2011–2013). Luc Van Gaal has also received grant support from the EU (Hepadip & Resolve consortium) and National Research Funds, Belgium.

Compliance with ethics guidelines

The analysis in this article is based on previously conducted studies, and does not involve any new studies of human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. GWT-TUD, Study Centre Prof. Hanefeld, Dresden Technical University, Fiedlerstr. 34, 01307, Dresden, Germany

    Markolf Hanefeld

  2. Sanofi, Bridgewater, NJ, USA

    Rachele Berria

  3. Novosys Health, Flemington, NJ, USA

    Jay Lin

  4. LMC Diabetes and Endocrinology, Toronto, Canada

    Ronnie Aronson

  5. Sainte-Marguerite University Hospital, Marseille, France

    Patrice Darmon

  6. University Hospital Llandough, Llandough, Cardiff, UK

    Marc Evans

  7. Antwerp University Hospital, Edegem-Antwerp, Belgium

    Luc Van Gaal

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  1. Markolf Hanefeld
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Correspondence to Markolf Hanefeld.

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Hanefeld, M., Berria, R., Lin, J. et al. Lixisenatide Treatment for Older Patients with Type 2 Diabetes Mellitus Uncontrolled on Oral Antidiabetics: Meta-Analysis of Five Randomized Controlled Trials. Adv Ther 31, 861–872 (2014). https://doi.org/10.1007/s12325-014-0146-4

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