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Outcome studies and safety as guide for decision making in treating patients with type 2 diabetes

Abstract

Cardiovascular disease is the leading cause of mortality in patients with diabetes. Over the past 20 years multiple CV outcome studies have been conducted assessing the cardiovascular benefits of tight glycemic control or of particular glucose lowering agents. Improved glycemic control per-se failed to significantly reduce the risk of adverse cardiovascular outcomes in the short term, and it is only after >15 years that a reduction in adverse CV outcomes with tight glycemic control was perceived. Moreover tight glycemic control and increased attendant hypoglycemia led to increased mortality observed in the ACCORD trial. These data highlighted the importance of setting individualized glycemic targets and assessing the CV safety of the individual glucose lowering agents. Three DPP-4 inhibitors have presented CV outcome data to date demonstrating overall CV safety yet the question of increased hospitalization for heart failure with saxagliptin remains unexplained. Lixisenatide was the first GLP-1 receptor agonist to publish CV outcome data which demonstrated overall safety. The SGLT-2 inhibitor empagliflozin demonstrated CV superiority and a reduction in all-cause mortality and hospitalization for heart failure vs. placebo via mechanisms which remain to be fully elucidated. The outcome studies, though large and costly, have had a considerable effect on diabetes guidelines, these now emphasizing the importance of individualization of care. The outcome studies will presumably influence the new guidelines and dictate better tailoring of the drug regimen to the individual patient, matching patient comorbidities to the accumulating data regarding the safety and efficacy of each drug and class.

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Conflict of interests

Avivit Cahn reports receipt of consulting fees and payment for lectures from: AstraZeneca, Boehringer Ingelheim, Elli Lilly, MSD, Novartis, Novo Nordisk and Sanofi.

Simona Cernea received payment for lectures from AstraZeneca, Berlin-Chemie Menarini, Eli Lilly, Novo Nordisk, Sanofi-Aventis, Servier Pharma, for clinical trial Steering Committee meetings as National Lead Investigator for DECLARE-TIMI58 from TIMI Study Group and support for travel to meetings from AstraZeneca, Eli Lilly, Sanofi-Aventis.

Itamar Raz reports: Advisory Board: AstraZeneca/Bristol-Meyers Squibb, Eli Lilly and Company, Merck Sharp & Dohme Limited, Novo Nordisk, Inc., Sanofi, Orgenesis, SmartZyme Innovation Ltd., Labstyle Innovations Ltd., Boehringer Ingelheim. Consultant: AstraZeneca/Bristol-Meyers Squibb, Insuline Medical, Gili Medical, Kamada Ltd., FuturRx Ltd., Nephrogenex Inc.,Diabetes Medical Center (Tel Aviv, Israel). Speaker’s Bureau: AstraZeneca/Bristol-Meyers Squibb, Eli Lilly and Company, Johnson & Johnson, Merck Sharp & Dohme Limited, Novartis Pharma AG, Novo Nordisk, Inc., Sanofi, Teva, Boehringer Ingelheim. Stock/Shareholder: Insuline Medical, Labstyle Innovations, SmartZyme Innovation Ltd., Orgenesis, Glucome Ltd.

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Cahn, A., Cernea, S. & Raz, I. Outcome studies and safety as guide for decision making in treating patients with type 2 diabetes. Rev Endocr Metab Disord 17, 117–127 (2016). https://doi.org/10.1007/s11154-016-9351-6

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  • DOI: https://doi.org/10.1007/s11154-016-9351-6

Keywords

  • Outcome studies
  • Cardiovascular
  • Safety
  • Type 2 diabetes
  • SGLT-2 inhibitors
  • DPP-4 inhibitors
  • GLP-1 receptor agonists
  • Insulin
  • Guidelines