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Lixisenatide resensitizes the insulin-secretory response to intravenous glucose challenge in people with type 2 diabetes--a study in both people with type 2 diabetes and healthy subjects.
Diabetes Obes Metab. 2014 Sep; 16(9):793-800.DO

Abstract

AIMS

Glucagon-like peptide-1 (GLP-1) receptor agonists improve blood glucose control by enhancing glucose-sensitive insulin release, delaying gastric emptying and reducing postprandial glucagon secretion. The studies reported here investigated the insulin response to an intravenous (iv) glucose challenge after injection of lixisenatide (LIXI) 20 µg or placebo.

METHODS

Two single-centre, double-blind, randomized, placebo-controlled, single-dose, crossover studies were performed in healthy subjects (HS) and people with type 2 diabetes mellitus (T2DM). Participants received subcutaneous LIXI or placebo 2 h before an iv glucose challenge. Study endpoints included first- and second-phase insulin response, insulin concentration (INS), glucagon response and glucose disposal rate (K(glucose)). LIXI exposure was measured over 12 h.

RESULTS

LIXI 20 µg reached maximum concentration after 2 h and resensitized first-phase insulin secretion by 2.8-fold in T2DM to rates comparable with those in HS on placebo, and raised second-phase insulin secretion by 1.6-fold in T2DM. INS rose correspondingly and glucose disposal was accelerated by 1.8-fold in T2DM. First-phase insulin secretion and glucose disposal were also augmented by LIXI in HS, whereas second-phase insulin secretion reduced blood glucose concentrations to below fasting levels and then ceased, accompanied by a rapid, short-lasting rise in glucagon. Otherwise, suppression of glucagon release subsequent to augmentation of insulin release was unaffected in T2DM and in HS.

CONCLUSIONS

LIXI resensitized the insulin response to an iv glucose challenge in people with T2DM, thereby accelerating glucose disposal to nearly physiological intensity, and did not impair counter-regulation to low glucose levels by glucagon.

Authors+Show Affiliations

Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24521245

Citation

Becker, R H A., et al. "Lixisenatide Resensitizes the Insulin-secretory Response to Intravenous Glucose Challenge in People With Type 2 Diabetes--a Study in Both People With Type 2 Diabetes and Healthy Subjects." Diabetes, Obesity & Metabolism, vol. 16, no. 9, 2014, pp. 793-800.
Becker RH, Stechl J, Msihid J, et al. Lixisenatide resensitizes the insulin-secretory response to intravenous glucose challenge in people with type 2 diabetes--a study in both people with type 2 diabetes and healthy subjects. Diabetes Obes Metab. 2014;16(9):793-800.
Becker, R. H., Stechl, J., Msihid, J., & Kapitza, C. (2014). Lixisenatide resensitizes the insulin-secretory response to intravenous glucose challenge in people with type 2 diabetes--a study in both people with type 2 diabetes and healthy subjects. Diabetes, Obesity & Metabolism, 16(9), 793-800. https://doi.org/10.1111/dom.12278
Becker RH, et al. Lixisenatide Resensitizes the Insulin-secretory Response to Intravenous Glucose Challenge in People With Type 2 Diabetes--a Study in Both People With Type 2 Diabetes and Healthy Subjects. Diabetes Obes Metab. 2014;16(9):793-800. PubMed PMID: 24521245.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lixisenatide resensitizes the insulin-secretory response to intravenous glucose challenge in people with type 2 diabetes--a study in both people with type 2 diabetes and healthy subjects. AU - Becker,R H A, AU - Stechl,J, AU - Msihid,J, AU - Kapitza,C, Y1 - 2014/03/25/ PY - 2013/09/13/received PY - 2013/10/15/revised PY - 2014/02/06/accepted PY - 2014/2/14/entrez PY - 2014/2/14/pubmed PY - 2016/5/7/medline KW - healthy subjects KW - insulin response KW - lixisenatide KW - pharmacodynamics KW - pharmacokinetics KW - type 2 diabetes mellitus SP - 793 EP - 800 JF - Diabetes, obesity & metabolism JO - Diabetes Obes Metab VL - 16 IS - 9 N2 - AIMS: Glucagon-like peptide-1 (GLP-1) receptor agonists improve blood glucose control by enhancing glucose-sensitive insulin release, delaying gastric emptying and reducing postprandial glucagon secretion. The studies reported here investigated the insulin response to an intravenous (iv) glucose challenge after injection of lixisenatide (LIXI) 20 µg or placebo. METHODS: Two single-centre, double-blind, randomized, placebo-controlled, single-dose, crossover studies were performed in healthy subjects (HS) and people with type 2 diabetes mellitus (T2DM). Participants received subcutaneous LIXI or placebo 2 h before an iv glucose challenge. Study endpoints included first- and second-phase insulin response, insulin concentration (INS), glucagon response and glucose disposal rate (K(glucose)). LIXI exposure was measured over 12 h. RESULTS: LIXI 20 µg reached maximum concentration after 2 h and resensitized first-phase insulin secretion by 2.8-fold in T2DM to rates comparable with those in HS on placebo, and raised second-phase insulin secretion by 1.6-fold in T2DM. INS rose correspondingly and glucose disposal was accelerated by 1.8-fold in T2DM. First-phase insulin secretion and glucose disposal were also augmented by LIXI in HS, whereas second-phase insulin secretion reduced blood glucose concentrations to below fasting levels and then ceased, accompanied by a rapid, short-lasting rise in glucagon. Otherwise, suppression of glucagon release subsequent to augmentation of insulin release was unaffected in T2DM and in HS. CONCLUSIONS: LIXI resensitized the insulin response to an iv glucose challenge in people with T2DM, thereby accelerating glucose disposal to nearly physiological intensity, and did not impair counter-regulation to low glucose levels by glucagon. SN - 1463-1326 UR - https://www.unboundmedicine.com/medline/citation/24521245/Lixisenatide_resensitizes_the_insulin_secretory_response_to_intravenous_glucose_challenge_in_people_with_type_2_diabetes__a_study_in_both_people_with_type_2_diabetes_and_healthy_subjects_ L2 - https://doi.org/10.1111/dom.12278 DB - PRIME DP - Unbound Medicine ER -