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Indirect comparison of lixisenatide versus neutral protamine Hagedorn insulin as add-on to metformin and sulphonylurea in patients with type 2 diabetes mellitus.
Ger Med Sci. 2014; 12:Doc14.GM

Abstract

OBJECTIVE

There is currently a lack of evidence from direct comparisons of treatment outcomes with lixisenatide versus neutral protamine Hagedorn (NPH)-insulin in type 2 diabetes mellitus (T2DM) patients with suboptimal glycaemic control with oral antidiabetic drugs (OADs). Hence, the current analysis indirectly compared available evidence on the risk of hypoglycaemia and weight change between lixisenatide and NPH-insulin based on randomized controlled trial (RCT) data with exenatide, insulin glargine and placebo as common references.

METHODS

A systematic search of PubMed, Embase, the Cochrane database and clinical registries identified English- and German-language articles published from January 1980 to October 2012 reporting data from RCTs. Only publications of trials that reported outcomes from 24 to 30 weeks comparing glucagon-like peptide-1 receptor agonists or basal insulin versus another antidiabetic agent or placebo were included. Hypoglycaemia, patients at glycated haemoglobin (HbA1c) target and discontinuations due to adverse events (AEs) were treated as binary variables, with risk ratios and odds ratios (ORs) calculated. HbA1c and body weight were treated as continuous variables with difference in mean change from baseline (MD) calculated. Meta-analyses were performed with random effects models and indirect comparisons were performed according to Bucher's method.

RESULTS

Seven RCTs (n=3,301 patients) comparing the efficacy and safety of lixisenatide, exenatide, insulin glargine and NPH-insulin with different antidiabetic treatments in adult patients with T2DM were included in the final analysis. In the adjusted indirect comparison, there was a significant difference in symptomatic hypoglycaemia (OR = 0.38; 95% CI = [0.17, 0.85]) and in confirmed hypoglycaemia (OR = 0.46; 95% CI = [0.22, 0.96]) favouring lixisenatide over NPH-insulin and comparable changes in HbA1c from baseline (MD = 0.07%; 95% CI = [-0.26%, 0.41%]). In contrast to NPH-insulin, there was a significant reduction in body weight with lixisenatide (MD = -3.62 kg; 95% CI = [-5.86 kg, -1.38 kg]) at study completion. The number of discontinuations due to AEs numerically favoured NPH-insulin over lixisenatide (OR = 2.64; 95% CI = [0.25, 27.96]), with a broad confidence interval.

CONCLUSIONS

Lixisenatide treatment was associated with a lower risk of hypoglycaemia and a greater weight loss compared with NPH-insulin. Glycaemic control with lixisenatide treatment was comparable with NPH-insulin. These data suggest that lixisenatide is a beneficial treatment option for T2DM patients with inadequate glycaemic control on OADs, and is associated with reduced risk of hypoglycaemia and weight gain.

Authors+Show Affiliations

Sanofi, Paris, France.Sanofi, Paris, France.Sanofi, Frankfurt, Germany.St. Elisabeth-Krankenhaus, Department of Endocrinology, Diabetology, Cardiology and General Medicine, Leipzig, Germany.Institute for Medical Statistics, Informatics and Epidemiology, University of Cologne, Germany.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

25332702

Citation

Fournier, Marie, et al. "Indirect Comparison of Lixisenatide Versus Neutral Protamine Hagedorn Insulin as Add-on to Metformin and Sulphonylurea in Patients With Type 2 Diabetes Mellitus." German Medical Science : GMS E-journal, vol. 12, 2014, pp. Doc14.
Fournier M, Germe M, Theobald K, et al. Indirect comparison of lixisenatide versus neutral protamine Hagedorn insulin as add-on to metformin and sulphonylurea in patients with type 2 diabetes mellitus. Ger Med Sci. 2014;12:Doc14.
Fournier, M., Germe, M., Theobald, K., Scholz, G. H., & Lehmacher, W. (2014). Indirect comparison of lixisenatide versus neutral protamine Hagedorn insulin as add-on to metformin and sulphonylurea in patients with type 2 diabetes mellitus. German Medical Science : GMS E-journal, 12, Doc14. https://doi.org/10.3205/000199
Fournier M, et al. Indirect Comparison of Lixisenatide Versus Neutral Protamine Hagedorn Insulin as Add-on to Metformin and Sulphonylurea in Patients With Type 2 Diabetes Mellitus. Ger Med Sci. 2014;12:Doc14. PubMed PMID: 25332702.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Indirect comparison of lixisenatide versus neutral protamine Hagedorn insulin as add-on to metformin and sulphonylurea in patients with type 2 diabetes mellitus. AU - Fournier,Marie, AU - Germe,Maeva, AU - Theobald,Karlheinz, AU - Scholz,Gerhard H, AU - Lehmacher,Walter, Y1 - 2014/10/16/ PY - 2013/08/22/received PY - 2014/09/11/revised PY - 2014/10/22/entrez PY - 2014/10/22/pubmed PY - 2015/7/3/medline KW - adjusted indirect comparison KW - basal insulin KW - hypoglycaemia KW - lixisenatide KW - type 2 diabetes KW - weight change SP - Doc14 EP - Doc14 JF - German medical science : GMS e-journal JO - Ger Med Sci VL - 12 N2 - OBJECTIVE: There is currently a lack of evidence from direct comparisons of treatment outcomes with lixisenatide versus neutral protamine Hagedorn (NPH)-insulin in type 2 diabetes mellitus (T2DM) patients with suboptimal glycaemic control with oral antidiabetic drugs (OADs). Hence, the current analysis indirectly compared available evidence on the risk of hypoglycaemia and weight change between lixisenatide and NPH-insulin based on randomized controlled trial (RCT) data with exenatide, insulin glargine and placebo as common references. METHODS: A systematic search of PubMed, Embase, the Cochrane database and clinical registries identified English- and German-language articles published from January 1980 to October 2012 reporting data from RCTs. Only publications of trials that reported outcomes from 24 to 30 weeks comparing glucagon-like peptide-1 receptor agonists or basal insulin versus another antidiabetic agent or placebo were included. Hypoglycaemia, patients at glycated haemoglobin (HbA1c) target and discontinuations due to adverse events (AEs) were treated as binary variables, with risk ratios and odds ratios (ORs) calculated. HbA1c and body weight were treated as continuous variables with difference in mean change from baseline (MD) calculated. Meta-analyses were performed with random effects models and indirect comparisons were performed according to Bucher's method. RESULTS: Seven RCTs (n=3,301 patients) comparing the efficacy and safety of lixisenatide, exenatide, insulin glargine and NPH-insulin with different antidiabetic treatments in adult patients with T2DM were included in the final analysis. In the adjusted indirect comparison, there was a significant difference in symptomatic hypoglycaemia (OR = 0.38; 95% CI = [0.17, 0.85]) and in confirmed hypoglycaemia (OR = 0.46; 95% CI = [0.22, 0.96]) favouring lixisenatide over NPH-insulin and comparable changes in HbA1c from baseline (MD = 0.07%; 95% CI = [-0.26%, 0.41%]). In contrast to NPH-insulin, there was a significant reduction in body weight with lixisenatide (MD = -3.62 kg; 95% CI = [-5.86 kg, -1.38 kg]) at study completion. The number of discontinuations due to AEs numerically favoured NPH-insulin over lixisenatide (OR = 2.64; 95% CI = [0.25, 27.96]), with a broad confidence interval. CONCLUSIONS: Lixisenatide treatment was associated with a lower risk of hypoglycaemia and a greater weight loss compared with NPH-insulin. Glycaemic control with lixisenatide treatment was comparable with NPH-insulin. These data suggest that lixisenatide is a beneficial treatment option for T2DM patients with inadequate glycaemic control on OADs, and is associated with reduced risk of hypoglycaemia and weight gain. SN - 1612-3174 UR - https://www.unboundmedicine.com/medline/citation/25332702/Indirect_comparison_of_lixisenatide_versus_neutral_protamine_Hagedorn_insulin_as_add_on_to_metformin_and_sulphonylurea_in_patients_with_type_2_diabetes_mellitus_ L2 - https://doi.org/10.3205/000199 DB - PRIME DP - Unbound Medicine ER -