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Paul Peter, Consultant, County Durham and Darlington NHS Foundation Trust

Steve Cleland, Consultant, Queen Elizabeth University Hospital, Glasgow

Alia Gilani, Health Inequalities Pharmacist, Nithsdale Surgery, Glasgow

Matt Hackett, GP, Weardale Practice, Bishop Auckland

Samina Ali , Prescribing Support Pharmacist, South Sector Headquarters, Glasgow

Denise Rabbette, Medicines Optimisation Manager, Thurrock, Grays

Minesh Unadkat, Takeda UK Ltd, London

Introduction

Clinical practice needs to adapt continually to new evidence on the effectiveness, safety profile, and costs of therapy. However, there is dramatic variation between geographical regions in the timing of implementing new clinical behaviours in response to national guidance.1 Since 2015, NICE guidance (NG28) for the management of type 2 diabetes (T2D) has advised commissioners and prescribers, ‘… when two options in the same class are appropriate, choose the option with the lowest acquisition cost’.2

Financial sustainability is key to ensure that the NHS Long-Term Plan is a service fit for future generations.3 In 2018/2019, in England, 12.5% of the total cost of prescribing was for the treatment of diabetes, which equates to a spend of £1075 million in primary care.4

NICE guidelines consider dipeptidyl peptidase-4 (DPP-4) inhibitors (alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin) as a class.2 A DPP-4 inhibitor in combination with metformin is one of the most widely used combination regimens to treat patients with T2D in the UK, with an estimated 7.1% of patients prescribed this combination, second only to the prescribing of a combination of sulphonylurea with metformin (7.4% of patients with T2D).5 Alogliptin is a DPP-4 inhibitor indicated in adults aged 18 years and older with T2D mellitus to improve glycaemic control in combination with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control.6 Here, we share our experiences of putting the NICE guideline NG28 into practice through switching appropriate patients with T2D from another DPP-4 inhibitor to alogliptin (the lowest acquisition cost option in this class, Table 1).

A systematic review of randomised clinical trials showed similar efficacy and safety for all DPP-4 inhibitors as combination therapy in patients with T2D.7 Alogliptin 25 mg daily has also been shown to have a similar efficacy and safety profile to other DPP-4 inhibitors in patients whose diabetes is inadequately controlled on metformin and sulfonylureas.8 Further, Strain and colleagues showed that switching UK primary care patients to alogliptin from other DPP-4 inhibitors did not result in clinically significant changes in glycaemic control and that, in general, treatment intensification was not needed following the switch.9 It is, therefore, reasonable to consider switching appropriate patients to alogliptin given the lower cost (Table 1), and comparable efficacy and tolerability profile, versus other DPP-4 inhibitors. 

Based on the evidence above, and as part of their healthcare planning for patients with diabetes, three clinical commissioning groups (CCGs)/local health boards (LHBs) chose to switch appropriate patients to alogliptin from alternative DPP-4 inhibitors. Given the different structures and resources available to each CCG/LHB, each developed its own process for the switch. The different structures, switch processes, and outcomes (in terms of costs and clinical benefits) unique to each CCG/LHB are presented below, followed by a discussion of the challenges encountered and how they were overcome.

We believe that by sharing insights gathered from individual experiences, comparing outcomes, and understanding the impact on patient care of switch policies, we can support the implementation of cost-saving initiatives and better use of NHS resources across England, where there is huge variation in the uptake of alogliptin.10

Table 1. Costs of DPP-4 inhibitors currently available in the UK11
DPP-4 inhibitor with/without metformin Net ingredient cost per patient treatment month (28 days’ treatment at standard dose)
Alogliptin £26.60
Alogliptin + metformin £26.60
Linagliptin  £33.26
Linagliptin + metformin £33.26
Saxagliptin £31.60
Saxagliptin + metformin  £31.60
Sitagliptin £33.26
Sitagliptin + metformin £33.26
Vildagliptin £33.35
Vildagliptin + metformin £33.30
Please consult the individual product SmPCs for full prescribing information 

Implementing the switch

Durham Dales, Easington and Sedgefield CCG

The switch to alogliptin in this CCG was part of a broader diabetes treatment review initiative, the County Durham and Darlington Diabetes Alliance, which aimed to improve long-term patient outcomes, upskill primary care physicians for the management of diabetes, and reduce referral levels. 

The CCG, covering 82 GP practices, was split into seven localities to manage the switch implementation. Each locality relied on a consultant-led, primary care-based team with a full-time diabetes specialist nurse working with a diabetes lead GP or practice nurse in the GP surgery to drive the programme. Monthly monitoring meetings were conducted in each locality. The non-clinical North East Commissioning Support (NECS) group also met with the primary care teams on a weekly basis to help implement the switch plan. A diabetes coordinator was appointed to liaise between primary care teams, consultants and practices, and to establish IT systems.  

The Durham Clinical Advisory Group (DCAG) developed a guidance document outlining patient treatment assessment criteria based on the effectiveness of existing DPP-4 inhibitor treatment and HbA1c levels. Practices performed their own patient audits, after which the GP/practice nurse contacted and explained the switch rationale to relevant patients. Consultants assisted with the initial stages of patient assessments and alogliptin switches. 

Switching of eligible patients began in early 2017. 

Greater Glasgow and Clyde LHB

The cost-saving potential of switching appropriate patients to alogliptin in this LHB, which included 240 practices, was identified by the Pharmacy Prescribing Support Unit (PPSU). The PPSU proposed a primary care-led switch programme to the Managed Clinical Network (MCN), which was subsequently endorsed. The plan was predominantly driven by prescribing support pharmacists, with support from a multidisciplinary team (MDT) of GPs, practice nurses, dietitians, diabetes specialist nurses, and podiatrists. Consultants assisted mainly at the beginning of the programme providing ad hoc support to pharmacists.

Switches were performed differently across practices. They were performed either on an opportunistic basis or following an annual treatment review for selected patients on DPP-4 inhibitors. In these selected patients, in addition to other clinical considerations, a switch was performed based on the HbA1c criteria in Table 2. 

The switch plan was initiated in May 2017 across the LHB but implementation started at different times across practices. Also, patients were advised to finish the supply of their current gliptin before starting alogliptin, so uptake levels reflected this.

Table 2. Switch criteria based on HbA1c measurements in preceding 3–6 months in patients receiving DPP-4 inhibitors
Reduction in HbA1c  in preceding 3–6 months? Within HbA1c target? Switch guidance
Yes Yes Switch to alogliptin
Yes  No Invite patient for review
No No Invite patient for review and a change in glucose-lowering therapy

Thurrock CCG

The high prevalence of T2D in young people in Thurrock CCG (even with a relatively young population), and the increasing costs associated with managing these patients, were key drivers for identifying cost savings while improving the delivery of early care in this population.

The CCG had a very active GP lead for diabetes who worked closely with the Medicines Management Team to review the evidence and potential cost savings that could be generated from a switch to alogliptin. The proposal was discussed at the South West Essex Diabetes Steering Group, which included representation from the Local Pharmaceutical Committee, and provider organisations (including community services, specialist diabetes teams, and the hospital endocrinologists), as well as, CCG GPs, commissioners, public health, and a lay representative. The Steering Group was keen to consider a therapeutic review rather than a switch, so that patients could receive a review of treatment effectiveness and compliance before making any changes. As a result, the Medicines Management Team was tasked with developing a standard operating procedure (SOP) for the review and agreeing this document through the governance structures in the CCG.

The proposal was discussed at the Thurrock Medicines Safety Group and, throughout the development of the SOP and complementary resources, engagement continued with the provider organisations and consultants, and the pharmacy team at the local hospital was also involved. This ensured that patients being admitted to hospital could be reviewed and switched where appropriate. Regular contact was maintained with key stakeholders to address any concerns or queries.

The CCG had a prescribing incentive scheme to help drive quality initiatives in practices, and because of the importance given to this project, the therapeutic review of DPP-4 inhibitors was included in the scheme. 

Once the project and the incentive scheme was signed off by the CCG Board, the resources (practice information, patient letters, and SOP) were circulated to practice-based GPs. This was supported by written information and followed up by the medicines team, who visited practices to explain the incentive scheme. The therapeutic review was optional, although by the end of the financial year all practices had engaged with the reviews, with varying levels of success.

Practices that engaged early in the process largely relied on practice diabetes nurses, who identified appropriate patients and led the switch. Some practices requested support from the Medicine Management Team to carry out audits and identify patients, but most practices kept ownership within their own teams. The Diabetes Steering Group was available throughout the switch programme to help address queries. Locality and practice meetings were held regularly to monitor the progress of the switch programme. 

Similar to the Greater Glasgow and Clyde LHB, some practices conducted the switch proactively by identifying appropriate patients and inviting them in for a treatment review, while other practices only intervened when the patient was next due in for review. The switch plan took 4 months to agree with all stakeholders, and patients started switching in 2016.

What were the outcomes of the switch programme?

Across the three CCG/LHBs discussed here, most patients were happy to engage in the switch following a primary care-led discussion regarding the cost-saving rationale for the switch and the comparable effectiveness across all DPP-4 inhibitors. 

Alogliptin prescription share, prescribing volume, and associated cost savings are shown for each CCG in Boxes 1, 2, and 3. Overall, increasing the prescription of alogliptin in place of alternative, more costly, DPP-4 inhibitors, led to considerable cost savings across all three CCG/LHBs in a relatively short timeframe. These figures were based on NHS prescription data to January 2019 for the CCGs in England, and to December 2018 for the Scottish LHB. Cost savings were calculated by Takeda UK Ltd. The methodology is described in Box 4.11

In most cases the switch programme prompted a patient treatment review. As a result, improvements in care also resulted from identifying patients not responding positively to DPP‑4 inhibitor treatment, and subsequently switching them to another treatment in a different treatment class. The patient treatment review also invited discussions with the patient on the importance of not just HbA1c levels, but other treatment targets including cholesterol and blood pressure. Therefore, the switch programme in general helped to ensure patient care was up to date and aligned to current treatment guidelines.

The switch programme also helped to improve partnerships between primary and secondary care networks. Upskilling of primary healthcare professionals was a corollary of the switch programme, which in turn reduced referrals to secondary care and associated time and costs.

Across the CCG/LHBs, savings made in response to the switch programme have generally been used towards improving local patient care and diabetes services. After exploring the outcomes of the switch programme, no negative impact has been reported to date.

Box 1. Alogliptin prescription share and cost savings following switch to alogliptin from alternative DPP-4 inhibitors in Durham Dales, Easington and Sedgefield CCG (to January 2019)

  • Alogliptin prescription share of total DPP-4 inhibitor usage changed from 10% at plan implementation to 64%
  • Alogliptin prescription share rose by more than 50% in under 2 years
  • Actual annual saving of £106,090 (as of January 2019)

Box 2. Alogliptin prescription share and cost savings following switch to alogliptin from alternative DPP-4 inhibitors in Greater Glasgow and Clyde LHB (to December 2018)

  • Alogliptin prescription share of total DPP-4 inhibitor usage changed from 3% at plan implementation to 54%
  • Alogliptin prescription share rose by more than 50% over a 17-month period
  • Actual annual saving of £316,577 (as of December 2018)

Box 3. Alogliptin prescription share and cost savings following switch to alogliptin from alternative DPP-4 inhibitors in Thurrock CCG (to January 2019)

  • Alogliptin prescription share of total DPP-4 inhibitor usage changed from 7% at plan implementation to 75%
  • Alogliptin prescription share rose by more than 68% in under 3 years
  • Actual annual saving of £103,811 (as of January 2019)

Box 4. Cost calculations

Cost-savings analyses were performed by Takeda UK Ltd12

DPP-4 inhibitor prescribing volume was modelled for each of the three CCGs/LHBs and data sets (one for each) were created based on two scenarios (NHS prescription data):

  • Historic data: actual prescription share (% of all DPP-4 inhibitor molecules including combinations of the active DPP-4 inhibitor with metformin where available; alogliptin, vildagliptin, sitagliptin, linagliptin and saxagliptin), and DPP-4 inhibitor prescription share calculated from moving quarterly total (MQT) patient treatment months (PTMs)
  • Estimated savings from pre-implementation: ‘Implementation date’ chosen as the month before significant uplift seen in alogliptin prescribing share. MQT DPP-4 inhibitor prescription shares from this date were pulled through intervening months. Actual MQT prescription share before ‘Implementation date’ remains the same
  • Moving annual total (MAT) DPP-4 inhibitor spend was calculated for the two scenarios by summing four quarterly MQT sales from known Net Ingredient Cost (NIC). Savings were calculated by subtracting from respective scenarios
  • Spending over the course of the switch programme was compared with what would have been spent if there had been no change from pre-implementation.

Overcoming the barriers to implementing the switch programme

Concerns over implementing the switch programme were evident across all CCG/LHBs. A fundamental challenge was overcoming the fear that a new switch initiative would mean an increase in primary care workload. Since the switch in most cases was carried out as part of a patient’s annual treatment review, any additional work incurred by the need to switch appropriate patients to alogliptin was minimal. This was further helped by the simple, like-for-like (one oral tablet, once-daily) medication switch process.

Each CCG/LHB had to work with the local structures and resources at their disposal to implement the switch. This was demonstrated by the two CCGs adopting a GP/nurse-driven approach, while the LHB implemented a pharmacist-driven approach. In the latter, there was a clear need to upskill pharmacists in the management of patients with T2D as there were too few diabetes specialist pharmacists to support the switch programme. Nevertheless, the pharmacist-driven switch programme was particularly successful in the Greater Glasgow and Clyde LHB as shown by the cost savings achieved to date in this LHB. Upskilling of GPs and nurses might also be needed given the rapidly changing treatment landscape for T2D and scarcity of time for primary care providers to keep up to date with treatment recommendations.

Although patients might have construed the switch as an exclusively cost-driven exercise, many practices sent letters or had face-to-face appointments with patients to explain the rationale for the switch and the comparable effectiveness across DPP-4 inhibitors. Some practices encountered cultural and/or language barriers when explaining the need behind the switch to patients, therefore, development of multilingual patient materials was considered. In most cases, patients were happy to proceed with the switch.

In the two CCGs, care was taken to ensure patients were prescribed the correct dose of alogliptin (and metformin) for their recorded estimated glomerular filtration rate (eGFR). In the Greater Glasgow and Clyde LHB, it was also noted that some practice GPs were not keen on switching to alogliptin in patients with renal impairment given the need to adjust the dose based on (eGFR). Therefore, the following switch criteria were also used: 

  • eGFR <60 mL/min/1.73 m2: patient switched to linagliptin
  • eGFR >60 mL/min/1.73 m2: patient switched to alogliptin.

Insights from case studies

A summary of the key learnings from conducting the switch programme is provided below.

  • A robust clinical evidence base is necessary to bring all stakeholders on board with the programme
  • Cost-saving illustrations help to show the predicted impact of the switch and should be shared with stakeholders
  • A clear roadmap of implementation, roles, and responsibilities based on local needs and available resources is needed for the smooth running of the programme
  • Identifying key stakeholder groups, and developing an engagement plan for them, will help with disseminating information and ensuring appropriate support is put in place
  • Approval for the switch plan from secondary care is key to ensure primary care uptake
  • Decision-support prescribing software can be helpful in supporting and reminding prescribers 
  • The development of central documents (SOPs and protocols) outlining key supporting information to implement the switch (e.g. patient inclusion/exclusion criteria) is needed to ensure consistent delivery of the programme
  • A supportive collaboration between primary and secondary care will help to upskill the primary care network, and thus improve their confidence to make appropriate switches
  • A personal approach for each patient is needed 
  • A patient engagement plan can help to ensure relevant information is communicated to patients.

Summary

Based on the collective experience across three CCG/LHBs, switching appropriate patients with T2D to alogliptin from alternative DPP-4 inhibitors is a relatively simple and cost-saving process that can be managed predominantly by primary healthcare professionals without having a major impact on workload.

Key points

  • According to NICE T2D guidelines (NG28), if two agents within the same class are appropriate, the option with the lowest acquisition cost should be chosen
  • Alogliptin has an established efficacy and safety profile comparable to other DPP-4 inhibitors,7,8 and is currently the DPP-4 inhibitor with the lowest acquisition cost in the UK
  • Switching appropriate patients to alogliptin from an alternative DPP-4 inhibitor is a relatively simple switch that is likely to be supported by primary care, secondary care, and local prescribing groups
  • Switching patients can be implemented efficiently and is associated with notable cost savings within a relatively short time-period (2–3 years)
  • A universal approach for switching appropriate patients is not possible: the process must be tailored according to local needs and available resources
  • The switch can be instigated as part of an annual treatment review plan for each eligible patient
  • No negative impact has been reported to date in response to the switch programme.

Acknowledgements

This article was initiated and funded by Takeda UK Ltd and included medical writing support provided by Grey Bear Consultancy. NHS Prescription Data analysis was conducted by Takeda UK Ltd. The article was reviewed by Takeda to ensure compliance with the ABPI code of practice.

Conflicts of interest

Paul Peter, Steve Cleland, Alia Gilani, Matt Hackett and Samina Ali received honoraria from Takeda UK Ltd during the development of this supplement. Some of the authors have also received consultancy fees from pharmaceutical companies, including Takeda UK Ltd, for activities other than the development of this supplement.

References

  1. Walker AJ, Pretis F, Powell-Smith A, Goldacre B. Variation in responsiveness to warranted behaviour change among NHS clinicians: novel implementation of change detection methods in longitudinal prescribing data. BMJ 2019; 367: l5205.
  2. NICE. Type 2 diabetes in adults: management. NICE Guideline 28. NICE, 2015 (last updated August 2019). Available at: www.nice.org.uk/guidance/ng28
  3. NHS England. NHS Long Term Plan. January 2019. Available at: www.longtermplan.nhs.uk
  4. NHS Digital. Prescribing for Diabetes in England 2008/09–2018/19. Available at: www.digital.nhs.uk/data-and-information/publications/statistical/prescribing-for-diabetes/2008-09—2018-19
  5. LPD. IQVIA Ltd. Incorporating data derived from THIN. A Cegedim Database Nov 2019.
  6. Takeda UK Ltd. Vipidia 6.25 mg, 12.5mg, and 25 mg film‑coated tablets. Summary of Product Characteristics. Available at:  www.medicines.org.uk/emc/search?q=vipidia (Accessed 6 February 2020).
  7. Craddy P, Palin H-J, Johnson KI. Comparative effectiveness of dipeptidylpeptidase-4 inhibitors in type 2 diabetes: a systematic review and mixed treatment comparison. Diabetes Ther 2014; 5: 1–41. These analyses were conducted and funded by Takeda.
  8. Kay S, Strickson A, Puelles J, et al. Comparative effectiveness of adding alogliptin to metformin plus sulfonylurea with other DPP-4 inhibitors in Type 2 diabetes: a systematic review and network meta-analysis. Diabetes Ther 2017; 8 (2): 251–273. 
  9. Strain WD, McEwan P, Howitt H, Meadowcroft S. Retrospective database analysis evaluating the clinical outcomes of changing treatment of people with Type 2 diabetes mellitus (T2DM) from other DPP-4 inhibitor therapy to alogliptin in a primary care setting. Diabetes Ther 2019; 10: 1499–1507.
  10. Open Prescribing. Search GP prescribing data. Items for Alogliptin vs Antidiabetic drugs by all CCGs. Available at: www.openprescribing.net/analyse/#org=CCG&numIds=0601023AK&denomIds=6.1.2&selectedTab=map (Accessed 27 January 2020)
  11. NHS Business Services Authority. NHS Prescription Service. Drug Tariff Part VIII. www.nhsbsa.nhs.uk/pharmacies-gp-practices-and-appliance-contractors/drug-tariff/drug-tariff-part-viii (Accessed 6 February 2020).
  12. Peter P, Unadkat M, Beusnard-Bee T. Cost-saving analyses when switching appropriate patients from existing DPP-4 inhibitors to alogliptin within licence – experiences across five CCGs/Health Boards. Presented at the JoMO–UKCPA Joint Meeting. Medicines Optimisation in Diabetes. May 2019.

This supplement has been commissioned and funded by Takeda UK Ltd, it has been developed in partnership with Grey Bear Consultancy and published by Guidelines in Practice. Takeda UK Ltd suggested the topic and authors, approved the scope documents, and carried out full medical approval on all materials to ensure compliance with regulations. The funding included honoraria for the authors. The views and opinions in this supplement are not necessarily those of Grey Bear or of Guidelines in Practice, its publisher, advisors, or advertisers. The copyright of Guidelines in Practice (including the Guidelines in Practice brand, logo, and the design and format of the journal) rests with MGP Ltd unless otherwise stated. No part of this publication may be reproduced in any form without the permission of the publisher.

UK/VIP/2001/0003a

Date of preparation: April 2020