Original research| Volume 16, ISSUE 2, P271-278, April 2022

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Metformin-based single pill drug combinations for type 2 diabetes in primary care England: A time trend analysis

Published:January 31, 2022DOI:


      • Single pill drug combinations can improve adherence & reduce pill burden.
      • A 1.4-fold increase in prescriptions of metformin-based combinations (2015–2020).
      • Metformin–sitagliptin & metformin–pioglitazone were the most & least prescribed drugs.
      • Metformin-SGLT2 inhibitors had seen a significant rise in their prescriptions.



      There has been an increase in prescribing and costs of oral hypoglycaemic agents in England and other countries. This study aims to investigate the trends in prescriptions, costs, and adverse events of metformin and metformin-based single pill drug combinations from 2015 to 2020 and explore why changes in use or cost are occurring.


      Prescriptions and costs data from Prescription Cost Analysis database and Interactive Drug Analysis Profiles presenting all suspected ADRs reported for each drug were examined. Pharmacy level prices were also obtained. Linear regression analysis was used to investigate the trends in prescribing and costs.


      Prescribing and costs of metformin-based single pill drug combinations (as a percent mean change per year) saw an increase of 8.78% (95% Cl: 7.45%, 10.11%, p = 0.001) and 5.17% (95% Cl: 2.13%, 8.22%, p = 0.009) on average each year, respectively. Metformin was the most prescribed monotherapy drug between 2015 and 2020. The cost of prescribing metformin (as a proportion of total oral hypoglycaemic agents) has been reduced from 30% in 2015 to 17% in 2020. Metformin-dipeptidyl peptidase-4 inhibitor (e.g., metformin–sitagliptin) combination was the most popular metformin-based single pill drug combination. The number of adverse drug reactions per million items dispensed shows that metformin has the lowest adverse drug reactions per million items compared to other oral hypoglycaemic drugs.


      Overall, an increase in prescription items can be seen for metformin-based single pill drug combinations along with an increase in their costs in primary care in England between 2015 and 2020. There was a declining trend for the number of ADRs reported per million prescription items dispensed for metformin-containing single pill combinations, even though their prescription rate increased.


      ADR (adverse drug reactions), DPP4 (dipeptidyl-peptidase 4), MHRA (Medicines and Healthcare Product Regulatory Agency), NHS (National Health Service), NICE (National Institute for Health and Care Excellence), PCA (Prescription Cost Analysis), SGLT2 (sodium–glucose co-transporter-2), UK (United Kingdom)


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