What to do with diabetes therapies when HbA1c lowering is inadequate: add, switch, or continue? A MASTERMIND study

MASTERMIND consortium, Andrew P. McGovern (Lead / Corresponding author), John M. Dennis, Beverley M. Shields, Andrew T. Hattersley, Ewan R. Pearson, Angus G. Jones

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Background: It is unclear what to do when people with type 2 diabetes have had no or a limited glycemic response to a recently introduced medication. Intra-individual HbA1c variability can obscure true response. Some guidelines suggest stopping apparently ineffective therapy, but no studies have addressed this issue.

Methods: In a retrospective cohort analysis using the UK Clinical Practice Research Datalink (CPRD), we assessed the outcome of 55,530 patients with type 2 diabetes starting their second or third non-insulin glucose-lowering medication, with a baseline HbA1c > 58 mmol/mol (7.5%). For those with no HbA1c improvement or a limited response at 6 months (HbA1c fall < 5.5 mmol/mol [0.5%]), we compared HbA1c 12 months later in those who continued their treatment unchanged, switched to new treatment, or added new treatment.

Results: An increase or a limited reduction in HbA1c was common, occurring in 21.9% (12,168/55,230), who had a mean HbA1c increase of 2.5 mmol/mol (0.2%). After this limited response, continuing therapy was more frequent (n = 9308; 74%) than switching (n = 1177; 9%) or adding (n = 2163; 17%). Twelve months later, in those who switched medication, HbA1c fell (- 6.8 mmol/mol [- 0.6%], 95%CI - 7.7, - 6.0) only slightly more than those who continued unchanged (- 5.1 mmol/mol [- 0.5%], 95%CI - 5.5, - 4.8). Adding another new therapy was associated with a substantially better reduction (- 12.4 mmol/mol [- 1.1%], 95%CI - 13.1, - 11.7). Propensity score-matched subgroups demonstrated similar results.

Conclusions: Where glucose-lowering therapy does not appear effective on initial HbA1c testing, changing agents does not improve glycemic control. The initial agent should be continued with another therapy added.

Original languageEnglish
Article number79
Pages (from-to)1-17
Number of pages17
JournalBMC Medicine
Issue number1
Publication statusPublished - 12 Apr 2019


  • Type 2 diabetes
  • Oral glucose-lowering medication
  • HbA1c
  • Addition
  • Switching
  • Continuation
  • Glycemic control


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