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Addition of a single short-acting insulin bolus to basal insulin-supported oral therapy: a systematic review of data on the basal-plus regimen
  1. Jochen Seufert1,
  2. Anja Borck2,
  3. Peter Bramlage3
  1. 1 Division of Endocrinology and Diabetoligy, Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  2. 2 Sanofi, Berlin, Germany
  3. 3 Institute for Pharmacology and Preventive Medicine, Cloppenburg, Germany
  1. Correspondence to Professor Jochen Seufert; jochenseufert{at}


We summarize here clinical and trial data on a once-daily administration of a single bolus to the meal with the largest expected postprandial glucose excursion (basal-plus), and comment on its clinical utility in the treatment of type 2 diabetes. A PubMed search of data published until September 2018 was taken into consideration and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Eighteen reports representing 15 studies were identified (age: 18–80 years; 50–890 patients; follow-up: 8 days to 60 weeks). Data suggest basal-plus is efficacious for improving glycemic control, with a low incidence of (severe) hypoglycemia and minor increases in bodyweight. The timing of short-acting insulin administration and use of different monitoring/titration approaches appear to have minimal impact. When compared with premixed insulin, basal-plus results in largely comparable outcomes. Compared with basal-bolus, it may result in non-inferior glycemic improvements with less weight gain, less hypoglycemia and fewer daily injections. A basal insulin/glucagon-like peptide-1 receptor agonist fixed ratio combination may offer several advantages over the basal-plus regimen, at the cost of gastrointestinal side effects. We conclude that the stepwise introduction of short-acting insulin via the basal-plus strategy represents a viable alternative to a full basal-bolus regimen and may help to overcome barriers associated with multiple injections and anticipated complexity of the insulin regimen.

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  • Contributors PB and JS drafted the first version of the manuscript and all authors revised the article for important intellectual content. All authors approved the final version for publication.

  • Funding Sanofi Aventis Deutschland GmbH supported the systematic literature search underlying this article.

  • Competing interests JS has attended Speaker’s Bureaux for AstraZeneca, Bristol-Myers Squibb, Bayer Healthcare, Berlin Chemie, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Lifescan, Merck Sharp & Dohme, Mundipharma, Novartis, Novo Nordisk, Pfizer, Sanofi and Takeda. PB has received research funding and honoraria for consultancy from AstraZeneca, Bristol-Myers Squibb, Novartis and Sanofi. AB is an employee of Sanofi.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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