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Diabetes currently affects more than 260,000 people in New Zealand, including a disproportionate number of Māori and Pacific people, with disease prevalence increasing year on year.[[1]] Approximately 90–95% of these cases are type 2 diabetes, a disease characterised by insulin resistance and insulin deficiency[[2]] and due, in part, to reduced activity of incretin hormones.[[3]] Importantly, poorly controlled type 2 diabetes is associated with significant micro- and macro-vascular damage such that cardiovascular disease is the greatest cause of mortality in this population.[[2]]

Treatment of type 2 diabetes requires a multifaceted approach, including diet, exercise and medication.[[4,5]] The goal of therapy is to lower glycated haemoglobin (HbA1c) levels to generally less than 53mmol/mol (or, where indicated, to an alternative target)[[6,7]] and to reduce cardiovascular and renal risk factors.[[8]] However, management of type 2 diabetes is often suboptimal, with recent data from the Waikato region suggesting that 60% and 32% of patients had an HbA1c value of greater than 53mmol/mol and 64mmol/mol, respectively.[[9]] Similarly, only a third of patients with type 2 diabetes were shown to have blood pressure and/or lipids at or below clinically recommended targets, and up to three quarters of all patients were obese, with a body mass index >30kg/m[[2]].[[9]] Concerningly, it was also shown that there was considerable ethnic inequity in diabetes outcomes, with Māori patients being significantly more likely to have elevated HbA1c[[9–11]] and a greater prevalence of end-stage renal disease, diabetic eye disease, amputation and cardiovascular disease.[[12–15]] Not only does this lead to increased healthcare costs,[[16]] but more importantly an ongoing reduced quality of life for these patients.

Where lifestyle management is insufficient to manage type 2 diabetes, glycaemic control is typically achieved through a stepwise escalation of glucose-lowering therapies.[[17]] Metformin is the usual first-line oral glycaemic agent, with additional agents being added as required.[[5,18]] Vildagliptin, a dipeptidyl peptidase IV inhibitor (DPPIVi) that lowers glucose levels by increasing the activity of endogenous incretins, was added to the funding schedule in New Zealand in October 2018.[[18]] Prior to the long-awaited introduction of sodium-glucose transport protein 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) this year, vildagliptin was the preferred second-line funded agent for patients with type 2 diabetes in New Zealand, as, unlike sulphonylureas, insulin and pioglitazone, it does not cause weight gain or hypoglycaemia. Moreover, vildagliptin is the only currently known agent that can delay the need for insulin therapy when taken in combination with metformin,[[22]] and it has been shown to be a suitable glucose-lowering agent in patients with impaired renal function[[23]] or established cardiovascular disease.[[24]]

However, unlike SGLT2i and GLP1RA, no randomised controlled trials have demonstrated that DPPIVi reduces weight or cardiovascular events, such as myocardial infarctions or strokes. As such, SGLT2i and GLP1RA are now the preferred second-line agents for high-risk patients with type 2 diabetes, though PHARMAC has restricted the use of these medications under special authority, including an ethnicity clause to increase the uptake in Māori and Pacific peoples, which has resulted in significant debate.[[25,26]] In particular, it is unknown whether needing to obtain special authority approval may increase disparities by adding a further barrier for those who already have reduced access to optimal medications in primary care.[[ 26]] Importantly, the impact of a special authority versus open access on medication use has never been explored in a New Zealand context, and the degree of variability seen with open access diabetes medications is largely unknown. Thus, the aim of this study was to determine the variability in open access vildagliptin use in patients with type 2 diabetes in the Waikato region. This was explored by evaluating the initial uptake and usage of vildagliptin (following funding approval in October 2018), including by patient age, gender, ethnicity and/or the affordability of access to primary care (ie, whether a practice was Very Low Cost Access (VLCA) or not).

Methods

Study design

This sub-study was part of a larger project assessing the quality of diabetes care in primary care in New Zealand (including diabetes medication prescribing and dispensing). The aim of this specific study was to characterise the initial use of vildagliptin in patients with type 2 diabetes in the 14-month period following PHARMAC’s approval of open access funding (October 2018). Ethics approval was granted by the New Zealand Health and Disability Ethics Committee (ref: 19/CEN/8).

Data sources

Primary care data were sourced directly from Hauraki Primary Healthcare Organisation (PHO; 17 practices), and then additionally from the electronic patient management systems of 14 general practices affiliated with Pinnacle PHO during September–December 2020.

National Health Index (NHI)-identified patient information was extracted for all patients who had a confirmed diagnosis (≥12 months) of diabetes (read code C10 (diabetes mellitus)) and were aged ≥18 years on 1 October 2017. Extracted data included age (at time of data collection), gender, ethnicity and HbA1c levels (1 October 2017–30 September 2018). Patient records were also checked against the Waikato District Health Board (WDHB) clinical records to retrieve missing demographic and diagnosis information and to exclude patients with confirmed type 1 diabetes. The latter were identified from the clinical register of the WDHB Regional Diabetes Service, where all had their disease confirmed by an endocrinologist as per standard international criteria. Additional NHI-matched HbA1c data were obtained from Pathlab New Zealand for the same time-period, and these were combined and then averaged to provide a mean value for each patient for the study period, which was then used for all analyses. Ethnicity was coded as Level 1 data as collated from the primary care and/or WDHB datasets, with prioritisation to manage multiple ethnicities.[[27]]

NHI-matched medication dispensing data were obtained from the Ministry of Health’s Pharmaceutical Collection database (1 October 2017–31 December 2019). This included the 12-month “pre-funding period” (to exclude any patients who were already receiving unfunded vildagliptin) and the 14-month “post-funding period” (to ascertain who had initiated vildagliptin therapy). An additional two months were included in the post-funding period to allow for any initial delays in general practitioner (GP) awareness of the new funding guidelines.[[28]]

Data processing

For inclusion in the data analysis, patients with type 2 diabetes had to have been dispensed a glucose-lowering therapy (oral hypoglycaemic agents and/or insulin) at least twice during the pre-funding period. This ensured that the dataset only included patients who were being actively treated with medication. Patients were then excluded from this sub-group if they had died between 1 October 2018 and 31 December 2019 (n=46), or if they had been dispensed unfunded vildagliptin at least once during the pre-funding period (n=14).

General practices were coded as “VLCA” or “non-VCLA” based on their published patient fee structures. HbA1c levels were categorised as <53mmol/mol (current glycaemic target),[[6,7]] 53–64mmol/mol (previous Ministry of Health target)[[8, 10]] and >64mmol/mol.

Statistical analyses

Initially, the type 2 diabetes cohort was characterised for the 12-month pre-funding period, including by gender, age group, ethnicity, VLCA status and diabetes medication regimen. Initial vildagliptin use during the 14-month post-funding period (October 2018–December 2019) was then similarly described. The date of the first vildagliptin dispensing was recorded for each patient, and the cumulative uptake of vildagliptin (time to first dispensing) were plotted in a series of cox-regression plots by age, gender, VLCA status, ethnicity, medication adherence and HbA1c levels. Subgroup differences were analysed with chi-squared test, student t-tests and Mann-Whitney U tests.

A cross-sectional logistic regression adjusted for gender, age, ethnicity, rurality, VLCA and diabetes treatment regimen was used to estimate the odds ratio of a patient being dispensed vildagliptin during the post-funding period.

All data analyses were performed in Python 3.7 using the Pandas 0.25.3, Scipy 1.3.2 and Statsmodels 0.10.2 libraries with significance accepted at P<0.05.

Results

We identified a total of 4,031 patients with type 2 diabetes who had been dispensed diabetes medication ≥2 times during the pre-funding period. After excluding patient deaths (n=46) and unfunded-vildagliptin users (n=14), the final pre-funding study cohort consisted of 3,971 patients.

The demographics of the pre-funding type 2 diabetes cohort (n=3,971) are shown in Table 1, with the median age of participants being 64.5±12.8 years. Medication used included metformin monotherapy (37.4%), insulin (alone or in combination; 31.7%) and/or medication combinations. The mean HbA1c was 64.4±18.1mmol/mol, with 40% of patients having an HbA1c of >64mmol/mol (Table 1).

Table 1: Characteristics of the type 2 diabetes study population prior to vildagliptin funding (n=3,971) and then for those patients who initiated therapy after October 2018 (n=724). View Table 1.

Use of vildagliptin during the 14-month post-funding approval

A total of 724/3,971 patients (18.2%) were dispensed vildagliptin at least once in the 14-month post-funding period (October 2018–December 2019). The mean HbA1c of these patients was 72.5±18.2mmol/mol compared to 62.6±17.6mmol/mol in those who did not initiate therapy (P<0.001). The characteristics of patients who started vildagliptin therapy are given in Table 1. Vildagliptin users were more likely to be younger, Asian or Pacific and have a higher HbA1c level (all P<0.001). Patients on more than one diabetes medication were more likely to be prescribed vildagliptin than patients on one medication (62.9% vs 45.8%, p<0.001), and there was no difference in use with regard to gender or the VLCA status of the practice. Overall, 79 of the 724 patients who initiated vildagliptin (12.2%) had a mean study HbA1c of <53mmol/mol, including 20 Asian (19.1%), 42 European (14.6%), nine Māori (5.0%), four Pacific (6.7%) and four Other (30.8%).

Initiation of vildagliptin therapy also varied considerably between general practices (Figure 1). The total proportion of type 2 diabetes patients within each practice who were dispensed vildagliptin at least once ranged from 0.0% to 82.4%. A small number of practices were shown to initiate vildagliptin therapy in a large proportion of patients, and four practices did not add vildagliptin to therapy at all (Figure 1).

Figure 1: Proportion of type 2 diabetes patients within each practice initiating vildagliptin therapy (October 2018–December 2019; blue bars) and mean time to initiation (orange line). Note that practices 28–31 had zero patients commencing vildagliptin therapy.

As shown in Table 2, logistic regression with adjustment for age, gender, medication regimen, VLCA status and HbA1c level showed that there was no difference in initiation of vildagliptin therapy between European, Pacific or other ethnic groups, though vildagliptin was less likely to be dispensed to Māori patients (OR 0.67, 95% CI: 0.53–0.84; P=0.001) and more likely to be dispensed to Asian patients (OR 1.34, 95% CI: 1.02–1.78; p=0.039). Similarly, vildagliptin was less likely to be dispensed to those aged >74 years (OR 0.69, 95% CI: 0.52–0.90; P=0.007), those with an HbA1c of <64mmol/mol and those receiving insulin (OR 0.64, 95% CI: 0.43–0.99; P=0.043; Table 2). However, younger patients were more likely to have vildagliptin added to therapy, as were patients on combination therapy (metformin plus sulfonylureas) compared to those dispensed metformin monotherapy.

Table 2: Odds ratio (with 95% confidence intervals)[[1]] of patients initiating vildagliptin therapy. View Table 2.

Cumulative uptake of vildagliptin (time to first dispensing)

The overall, unadjusted cumulative uptake of vildagliptin after October 2018 by ethnicity, VLCA status and HbA1c band is shown in Figure 2. Māori and European patients had a comparable uptake of vildagliptin during the 14-month post-funding period (P=0.08), and uptake for both was lower than for Asian, Pacific and other ethnic groups. VLCA practices were faster to initiate vildagliptin therapy (P=0.02), but the proportion of patients using the medication in VLCA and non-VLCA practices was comparable by December 2020 (approximately 400 days). Initiation of vildagliptin therapy did not differ between males and females but was slower in older patients (P<0.05). As expected, vildagliptin uptake was highest in those with an HbA1c of >64mmol/mol (P<0.01; Figure 1).

Figure 2: Mean time to first dispensing (with 95% confidence intervals) of vildagliptin following PHARMAC’s approval of open access funding in October 2018 (A) by ethnicity, (B) by VLCA status and (C) by HbA1c group (mmol/mol). View Figure 2.

The mean overall time to first vildagliptin dispensing was 192.1±112.4 days, and nine of the 31 general practices (29%) had a mean time to vildagliptin use of less than 192.1 days (Table 2).

Discussion

Our study shows that initiation and/or early use of vildagliptin was associated with inequity in patients with type 2 diabetes in the Waikato region, with Māori being less likely to receive the medication after adjustment for age, gender, HbA1c level and VLCA status. This agrees with other studies that have shown that Māori are less likely to be dispensed oral diabetes medications,[[29–31]] with many researchers suggesting that this is due to Māori being less engaged with primary care.[[32,33]] The barriers for Māori accessing primary care (and healthcare in general) are well recognised in New Zealand,[[34–36]] and a recent report shows that access to medications has not improved for Māori in recent years.[[37]] It is clear that substantially more work is required to provide equitable access to health services in New Zealand.[[36,38]]

One way to improve access is by making primary care affordable for those in need.[[38]] For example, the VLCA scheme initiated in 2002 provides additional funding (and subsequently lower patient fees) to general practices where at least 50% of the enrolled patients are deemed “high needs”.[[39,40]] Indeed, we show that the mean time to the first dispensing of vildagliptin was lower in VLCA compared to non-VLCA practices, suggesting that that the lower costs associated with these practices may result in a faster uptake of new medications because of increased access to primary care (though there was no difference in the proportion of patients initiating therapy after 12 months). However, our study also showed that the VLCA status of the practice did not influence the proportion of patients with type 2 diabetes who initiated vildagliptin therapy during the 14-month post-funding period. Rather, we demonstrate that the practice (and therefore the GPs themselves) may be one of the most important factors that contribute to variability in initiation of therapy. Similarly, other studies have reported on the substantial variations seen in diabetes medication prescribing in primary care (particularly in the use of second-line medications),[[41,42]] and it has been suggested that this may be due to changes in, and/or lack of ease of use of, national policies and prescribing guidelines,[[42]] as well as differences in clinician-specific and environmental factors.[[43]]

Education has also been identified as a significant factor to consider when evaluating the initiation and update of newly approved medications. Primary care guidelines may change, for example, but doctors are often reluctant to immediately implement these changes; they cite reasons such as lack of evidence, organisational constraints, lack of knowledge about the guideline recommendations[[44]] and the uniqueness of individual cases as reasons.[[45]] Further, updated and/or new data are often not available via a central resource. Indeed, during the study period, the national guidelines on the management of type 2 diabetes were not updated to include vildagliptin,[[46]] and other resources, such as those published by the Best Practice Advocacy Centre (BPAC)[[47]] and the New Zealand Society for the Study of Diabetes,[[48]] may not have reached all prescribers.[[5,17,18,47]] Collectively, these issues cause discontinuity and variation in disease management, and this is congruent with our finding that the proportion of patients who initiated vildagliptin by practice varied from 0.0% to 82.4%.

Importantly, our study showed that, while the time to initiation of vildagliptin therapy was comparable for Māori and European, Māori were less likely to have vildagliptin dispensed. This has impact for the funding and access models used for the provision of other new medications in New Zealand: in particular, whether the ethnicity clause of the special authority criteria for SGLT2i and GLP1RA reduces the disparities in access to glucose-lowering therapies in Aotearoa New Zealand.[[49]] Although the full impact of the special authority criteria will not be known for some time, the data from the current study suggest that inter-practice variability in prescribing may be a significant contributor to medication use over and above whether a medication is available open access or via special authority, and it could be that GP education is required to increase new medication use for Māori patients.

Our study is the first to review the initiation and use of funded vildagliptin in a New Zealand population, though we do note the following study limitations. Firstly, we reviewed the use of vildagliptin without any assessment of whether the medication was clinically indicated. For inclusion in our study, patients with type 2 diabetes needed to have been receiving oral hypoglycaemic therapy, but it is possible that some of these had already met their individual clinical targets and thus did not require escalation of therapy. Indeed, 12.2% of those who initiated vildagliptin in our study had a most recent HbA1c of <53mmol/mol. Further, we did not include patients who had an HbA1c of >53mmol/mol and were not taking any glucose-lowering therapies for legitimate reasons. Thus, further work is required to evaluate the uptake and use of this drug in patients who meet the clinical threshold for use.

Secondly, our study involved only those patients dispensed two or more medications during the study period—that is, patients indicated as already accessing and/or engaging with primary healthcare. Our dataset excluded 1,118 patients who did not meet this criterion, but we do not know the reasons behind why patients had <2 dispensings (eg, it was not clinically indicated, the patient was newly diagnosed and/or the patient had not visited their GP). This warrants further investigation, as at least some of these patients would likely benefit from the use of glucose-lowering therapies.

Our study was also restricted to only those practices in the Waikato region affiliated with two specific PHOs; we had no information about whether patients had moved out of region or changed PHOs during the study period. The inclusion of additional practices, particularly those from the National Hauora Coalition (NHC; the third PHO in the Waikato region) may have altered our findings because of the inclusion of Māori-led healthcare providers. As nearly a third of all patients who initiated vildagliptin in our study were Māori, we suggest that our study was not skewed by a lack of inclusion of NHC patient data. However, we do acknowledge that the Māori-led healthcare providers may have been more proactive at prescribing medication to Māori patients, and where possible these data should be included in future evaluations.

Fourth, our patient cohort was also largely defined using primary care read codes, which can be inaccurate. It is possible that the accuracy of these data may be different for different patient groups (eg, by ethnicity, VLCA status, etc) and the reliability of using read codes to define patient diagnoses should be validated before larger studies are undertaken.

Fifth, although our results preliminarily suggest that dispensing of vildagliptin is not reduced in Pacific patients compared to European, we must note that our cohort study was not powered appropriately to assess this outcome. As such, we suggest that further studies comprising larger numbers of Pacific type 2 diabetes patients are warranted. And lastly, it is possible that practice-level factors (eg, nurse-led clinics and/or onsite pharmacists) might influence the usage and uptake of new agents. This too should be evaluated in future studies.

In conclusion, there appears to be inequity in the initial uptake and use of open access vildagliptin in the Waikato region.

Authorship credit

LC, RL, RK and RP all contributed to the conception and design of the study, as well as interpretation of data. LC collected the data and CM analysed it. LC, CM, RP and RL drafted the article for publication. All authors revised it for critically important intellectual content. All authors give their approval for publication.

Summary

Abstract

Aim

To determine what the variation was in the initial use of vildagliptin in patients with type 2 diabetes following approval of open access funding in October 2018, including by ethnicity, gender, age, funding model and patient HbA1c levels.

Method

Data were collected from 31 general practices for all adult patients with type 2 diabetes. National Health Index-matched medication data were obtained from the national Pharmaceutical Collection. Patients were included for analysis if they had received at least one diabetes medication in the 12 months prior to funding approval for vildagliptin. The proportion of patients who initiated vildagliptin therapy following open access funding approval was then evaluated, as was the time taken until the first dispensing (days since funding approval).

Results

A total of 724 of 3,971 (18.2%) of patients initiated vildagliptin therapy; mean time to first dispensing was 192.1±112.4 days. In logistic regression, Asian patients were more likely and Māori less likely to receive vildagliptin than Europeans. Younger patients and those with an HbA1c of >64mmol/mol were also more likely to initiate therapy. Vildagliptin use by general practice ranged from 0.0–82.4%.

Conclusion

Despite open access funding, there was inequity in the initial use of vildagliptin. Substantial variation by general practice indicates that practitioner education may be needed to ensure appropriate and early adoption of new diabetes medications.

Author Information

Lynne Chepulis: Medical Research Centre, University of Waikato, Hamilton. Christopher Mayo: Faculty of Medical and Health Sciences, University of Auckland, Auckland. Ryan Paul: Medical Research Centre, University of Waikato, Hamilton; Waikato District Health Board, Hamilton. Rawiri Keenan: Medical Research Centre, University of Waikato, Hamilton. Ross Lawrenson: Medical Research Centre, University of Waikato, Hamilton; Waikato District Health Board, Hamilton.

Acknowledgements

We would like to thank the New Zealand College of General Practitioners for funding this study.

Correspondence

Lynne Chepulis, Waikato Medical Research Centre, University of Waikato, Private Bag 3105, Hamilton, New Zealand; +64 7 8384193

Correspondence Email

lynnec@waikato.ac.nz

Competing Interests

Nil.

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47. Best Practice Advocacy Centre New Zealand. A rising tide of type 2 diabetes in younger people: what can primary care do? [Internet]. 2019 [cited 2019 Aug]. Available from: https://bpac.org.nz/2018/diabetes.aspx

48. Paul R. Type 2 Diabetes management guidelines: 2021 recommendations from NZSSD [Internet]. 2021 [cited 2021 Jun]. Available from: http://t2dm.nzssd.org.nz

49. Pharmaceutical Management Agency (Pharmac). PHARMAC to fund new diabetes medicines with amended Special Authority criteria [Internet]. 2021 [cited 2021 Jul]. Available from: pharmac.govt.nz

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Diabetes currently affects more than 260,000 people in New Zealand, including a disproportionate number of Māori and Pacific people, with disease prevalence increasing year on year.[[1]] Approximately 90–95% of these cases are type 2 diabetes, a disease characterised by insulin resistance and insulin deficiency[[2]] and due, in part, to reduced activity of incretin hormones.[[3]] Importantly, poorly controlled type 2 diabetes is associated with significant micro- and macro-vascular damage such that cardiovascular disease is the greatest cause of mortality in this population.[[2]]

Treatment of type 2 diabetes requires a multifaceted approach, including diet, exercise and medication.[[4,5]] The goal of therapy is to lower glycated haemoglobin (HbA1c) levels to generally less than 53mmol/mol (or, where indicated, to an alternative target)[[6,7]] and to reduce cardiovascular and renal risk factors.[[8]] However, management of type 2 diabetes is often suboptimal, with recent data from the Waikato region suggesting that 60% and 32% of patients had an HbA1c value of greater than 53mmol/mol and 64mmol/mol, respectively.[[9]] Similarly, only a third of patients with type 2 diabetes were shown to have blood pressure and/or lipids at or below clinically recommended targets, and up to three quarters of all patients were obese, with a body mass index >30kg/m[[2]].[[9]] Concerningly, it was also shown that there was considerable ethnic inequity in diabetes outcomes, with Māori patients being significantly more likely to have elevated HbA1c[[9–11]] and a greater prevalence of end-stage renal disease, diabetic eye disease, amputation and cardiovascular disease.[[12–15]] Not only does this lead to increased healthcare costs,[[16]] but more importantly an ongoing reduced quality of life for these patients.

Where lifestyle management is insufficient to manage type 2 diabetes, glycaemic control is typically achieved through a stepwise escalation of glucose-lowering therapies.[[17]] Metformin is the usual first-line oral glycaemic agent, with additional agents being added as required.[[5,18]] Vildagliptin, a dipeptidyl peptidase IV inhibitor (DPPIVi) that lowers glucose levels by increasing the activity of endogenous incretins, was added to the funding schedule in New Zealand in October 2018.[[18]] Prior to the long-awaited introduction of sodium-glucose transport protein 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) this year, vildagliptin was the preferred second-line funded agent for patients with type 2 diabetes in New Zealand, as, unlike sulphonylureas, insulin and pioglitazone, it does not cause weight gain or hypoglycaemia. Moreover, vildagliptin is the only currently known agent that can delay the need for insulin therapy when taken in combination with metformin,[[22]] and it has been shown to be a suitable glucose-lowering agent in patients with impaired renal function[[23]] or established cardiovascular disease.[[24]]

However, unlike SGLT2i and GLP1RA, no randomised controlled trials have demonstrated that DPPIVi reduces weight or cardiovascular events, such as myocardial infarctions or strokes. As such, SGLT2i and GLP1RA are now the preferred second-line agents for high-risk patients with type 2 diabetes, though PHARMAC has restricted the use of these medications under special authority, including an ethnicity clause to increase the uptake in Māori and Pacific peoples, which has resulted in significant debate.[[25,26]] In particular, it is unknown whether needing to obtain special authority approval may increase disparities by adding a further barrier for those who already have reduced access to optimal medications in primary care.[[ 26]] Importantly, the impact of a special authority versus open access on medication use has never been explored in a New Zealand context, and the degree of variability seen with open access diabetes medications is largely unknown. Thus, the aim of this study was to determine the variability in open access vildagliptin use in patients with type 2 diabetes in the Waikato region. This was explored by evaluating the initial uptake and usage of vildagliptin (following funding approval in October 2018), including by patient age, gender, ethnicity and/or the affordability of access to primary care (ie, whether a practice was Very Low Cost Access (VLCA) or not).

Methods

Study design

This sub-study was part of a larger project assessing the quality of diabetes care in primary care in New Zealand (including diabetes medication prescribing and dispensing). The aim of this specific study was to characterise the initial use of vildagliptin in patients with type 2 diabetes in the 14-month period following PHARMAC’s approval of open access funding (October 2018). Ethics approval was granted by the New Zealand Health and Disability Ethics Committee (ref: 19/CEN/8).

Data sources

Primary care data were sourced directly from Hauraki Primary Healthcare Organisation (PHO; 17 practices), and then additionally from the electronic patient management systems of 14 general practices affiliated with Pinnacle PHO during September–December 2020.

National Health Index (NHI)-identified patient information was extracted for all patients who had a confirmed diagnosis (≥12 months) of diabetes (read code C10 (diabetes mellitus)) and were aged ≥18 years on 1 October 2017. Extracted data included age (at time of data collection), gender, ethnicity and HbA1c levels (1 October 2017–30 September 2018). Patient records were also checked against the Waikato District Health Board (WDHB) clinical records to retrieve missing demographic and diagnosis information and to exclude patients with confirmed type 1 diabetes. The latter were identified from the clinical register of the WDHB Regional Diabetes Service, where all had their disease confirmed by an endocrinologist as per standard international criteria. Additional NHI-matched HbA1c data were obtained from Pathlab New Zealand for the same time-period, and these were combined and then averaged to provide a mean value for each patient for the study period, which was then used for all analyses. Ethnicity was coded as Level 1 data as collated from the primary care and/or WDHB datasets, with prioritisation to manage multiple ethnicities.[[27]]

NHI-matched medication dispensing data were obtained from the Ministry of Health’s Pharmaceutical Collection database (1 October 2017–31 December 2019). This included the 12-month “pre-funding period” (to exclude any patients who were already receiving unfunded vildagliptin) and the 14-month “post-funding period” (to ascertain who had initiated vildagliptin therapy). An additional two months were included in the post-funding period to allow for any initial delays in general practitioner (GP) awareness of the new funding guidelines.[[28]]

Data processing

For inclusion in the data analysis, patients with type 2 diabetes had to have been dispensed a glucose-lowering therapy (oral hypoglycaemic agents and/or insulin) at least twice during the pre-funding period. This ensured that the dataset only included patients who were being actively treated with medication. Patients were then excluded from this sub-group if they had died between 1 October 2018 and 31 December 2019 (n=46), or if they had been dispensed unfunded vildagliptin at least once during the pre-funding period (n=14).

General practices were coded as “VLCA” or “non-VCLA” based on their published patient fee structures. HbA1c levels were categorised as <53mmol/mol (current glycaemic target),[[6,7]] 53–64mmol/mol (previous Ministry of Health target)[[8, 10]] and >64mmol/mol.

Statistical analyses

Initially, the type 2 diabetes cohort was characterised for the 12-month pre-funding period, including by gender, age group, ethnicity, VLCA status and diabetes medication regimen. Initial vildagliptin use during the 14-month post-funding period (October 2018–December 2019) was then similarly described. The date of the first vildagliptin dispensing was recorded for each patient, and the cumulative uptake of vildagliptin (time to first dispensing) were plotted in a series of cox-regression plots by age, gender, VLCA status, ethnicity, medication adherence and HbA1c levels. Subgroup differences were analysed with chi-squared test, student t-tests and Mann-Whitney U tests.

A cross-sectional logistic regression adjusted for gender, age, ethnicity, rurality, VLCA and diabetes treatment regimen was used to estimate the odds ratio of a patient being dispensed vildagliptin during the post-funding period.

All data analyses were performed in Python 3.7 using the Pandas 0.25.3, Scipy 1.3.2 and Statsmodels 0.10.2 libraries with significance accepted at P<0.05.

Results

We identified a total of 4,031 patients with type 2 diabetes who had been dispensed diabetes medication ≥2 times during the pre-funding period. After excluding patient deaths (n=46) and unfunded-vildagliptin users (n=14), the final pre-funding study cohort consisted of 3,971 patients.

The demographics of the pre-funding type 2 diabetes cohort (n=3,971) are shown in Table 1, with the median age of participants being 64.5±12.8 years. Medication used included metformin monotherapy (37.4%), insulin (alone or in combination; 31.7%) and/or medication combinations. The mean HbA1c was 64.4±18.1mmol/mol, with 40% of patients having an HbA1c of >64mmol/mol (Table 1).

Table 1: Characteristics of the type 2 diabetes study population prior to vildagliptin funding (n=3,971) and then for those patients who initiated therapy after October 2018 (n=724). View Table 1.

Use of vildagliptin during the 14-month post-funding approval

A total of 724/3,971 patients (18.2%) were dispensed vildagliptin at least once in the 14-month post-funding period (October 2018–December 2019). The mean HbA1c of these patients was 72.5±18.2mmol/mol compared to 62.6±17.6mmol/mol in those who did not initiate therapy (P<0.001). The characteristics of patients who started vildagliptin therapy are given in Table 1. Vildagliptin users were more likely to be younger, Asian or Pacific and have a higher HbA1c level (all P<0.001). Patients on more than one diabetes medication were more likely to be prescribed vildagliptin than patients on one medication (62.9% vs 45.8%, p<0.001), and there was no difference in use with regard to gender or the VLCA status of the practice. Overall, 79 of the 724 patients who initiated vildagliptin (12.2%) had a mean study HbA1c of <53mmol/mol, including 20 Asian (19.1%), 42 European (14.6%), nine Māori (5.0%), four Pacific (6.7%) and four Other (30.8%).

Initiation of vildagliptin therapy also varied considerably between general practices (Figure 1). The total proportion of type 2 diabetes patients within each practice who were dispensed vildagliptin at least once ranged from 0.0% to 82.4%. A small number of practices were shown to initiate vildagliptin therapy in a large proportion of patients, and four practices did not add vildagliptin to therapy at all (Figure 1).

Figure 1: Proportion of type 2 diabetes patients within each practice initiating vildagliptin therapy (October 2018–December 2019; blue bars) and mean time to initiation (orange line). Note that practices 28–31 had zero patients commencing vildagliptin therapy.

As shown in Table 2, logistic regression with adjustment for age, gender, medication regimen, VLCA status and HbA1c level showed that there was no difference in initiation of vildagliptin therapy between European, Pacific or other ethnic groups, though vildagliptin was less likely to be dispensed to Māori patients (OR 0.67, 95% CI: 0.53–0.84; P=0.001) and more likely to be dispensed to Asian patients (OR 1.34, 95% CI: 1.02–1.78; p=0.039). Similarly, vildagliptin was less likely to be dispensed to those aged >74 years (OR 0.69, 95% CI: 0.52–0.90; P=0.007), those with an HbA1c of <64mmol/mol and those receiving insulin (OR 0.64, 95% CI: 0.43–0.99; P=0.043; Table 2). However, younger patients were more likely to have vildagliptin added to therapy, as were patients on combination therapy (metformin plus sulfonylureas) compared to those dispensed metformin monotherapy.

Table 2: Odds ratio (with 95% confidence intervals)[[1]] of patients initiating vildagliptin therapy. View Table 2.

Cumulative uptake of vildagliptin (time to first dispensing)

The overall, unadjusted cumulative uptake of vildagliptin after October 2018 by ethnicity, VLCA status and HbA1c band is shown in Figure 2. Māori and European patients had a comparable uptake of vildagliptin during the 14-month post-funding period (P=0.08), and uptake for both was lower than for Asian, Pacific and other ethnic groups. VLCA practices were faster to initiate vildagliptin therapy (P=0.02), but the proportion of patients using the medication in VLCA and non-VLCA practices was comparable by December 2020 (approximately 400 days). Initiation of vildagliptin therapy did not differ between males and females but was slower in older patients (P<0.05). As expected, vildagliptin uptake was highest in those with an HbA1c of >64mmol/mol (P<0.01; Figure 1).

Figure 2: Mean time to first dispensing (with 95% confidence intervals) of vildagliptin following PHARMAC’s approval of open access funding in October 2018 (A) by ethnicity, (B) by VLCA status and (C) by HbA1c group (mmol/mol). View Figure 2.

The mean overall time to first vildagliptin dispensing was 192.1±112.4 days, and nine of the 31 general practices (29%) had a mean time to vildagliptin use of less than 192.1 days (Table 2).

Discussion

Our study shows that initiation and/or early use of vildagliptin was associated with inequity in patients with type 2 diabetes in the Waikato region, with Māori being less likely to receive the medication after adjustment for age, gender, HbA1c level and VLCA status. This agrees with other studies that have shown that Māori are less likely to be dispensed oral diabetes medications,[[29–31]] with many researchers suggesting that this is due to Māori being less engaged with primary care.[[32,33]] The barriers for Māori accessing primary care (and healthcare in general) are well recognised in New Zealand,[[34–36]] and a recent report shows that access to medications has not improved for Māori in recent years.[[37]] It is clear that substantially more work is required to provide equitable access to health services in New Zealand.[[36,38]]

One way to improve access is by making primary care affordable for those in need.[[38]] For example, the VLCA scheme initiated in 2002 provides additional funding (and subsequently lower patient fees) to general practices where at least 50% of the enrolled patients are deemed “high needs”.[[39,40]] Indeed, we show that the mean time to the first dispensing of vildagliptin was lower in VLCA compared to non-VLCA practices, suggesting that that the lower costs associated with these practices may result in a faster uptake of new medications because of increased access to primary care (though there was no difference in the proportion of patients initiating therapy after 12 months). However, our study also showed that the VLCA status of the practice did not influence the proportion of patients with type 2 diabetes who initiated vildagliptin therapy during the 14-month post-funding period. Rather, we demonstrate that the practice (and therefore the GPs themselves) may be one of the most important factors that contribute to variability in initiation of therapy. Similarly, other studies have reported on the substantial variations seen in diabetes medication prescribing in primary care (particularly in the use of second-line medications),[[41,42]] and it has been suggested that this may be due to changes in, and/or lack of ease of use of, national policies and prescribing guidelines,[[42]] as well as differences in clinician-specific and environmental factors.[[43]]

Education has also been identified as a significant factor to consider when evaluating the initiation and update of newly approved medications. Primary care guidelines may change, for example, but doctors are often reluctant to immediately implement these changes; they cite reasons such as lack of evidence, organisational constraints, lack of knowledge about the guideline recommendations[[44]] and the uniqueness of individual cases as reasons.[[45]] Further, updated and/or new data are often not available via a central resource. Indeed, during the study period, the national guidelines on the management of type 2 diabetes were not updated to include vildagliptin,[[46]] and other resources, such as those published by the Best Practice Advocacy Centre (BPAC)[[47]] and the New Zealand Society for the Study of Diabetes,[[48]] may not have reached all prescribers.[[5,17,18,47]] Collectively, these issues cause discontinuity and variation in disease management, and this is congruent with our finding that the proportion of patients who initiated vildagliptin by practice varied from 0.0% to 82.4%.

Importantly, our study showed that, while the time to initiation of vildagliptin therapy was comparable for Māori and European, Māori were less likely to have vildagliptin dispensed. This has impact for the funding and access models used for the provision of other new medications in New Zealand: in particular, whether the ethnicity clause of the special authority criteria for SGLT2i and GLP1RA reduces the disparities in access to glucose-lowering therapies in Aotearoa New Zealand.[[49]] Although the full impact of the special authority criteria will not be known for some time, the data from the current study suggest that inter-practice variability in prescribing may be a significant contributor to medication use over and above whether a medication is available open access or via special authority, and it could be that GP education is required to increase new medication use for Māori patients.

Our study is the first to review the initiation and use of funded vildagliptin in a New Zealand population, though we do note the following study limitations. Firstly, we reviewed the use of vildagliptin without any assessment of whether the medication was clinically indicated. For inclusion in our study, patients with type 2 diabetes needed to have been receiving oral hypoglycaemic therapy, but it is possible that some of these had already met their individual clinical targets and thus did not require escalation of therapy. Indeed, 12.2% of those who initiated vildagliptin in our study had a most recent HbA1c of <53mmol/mol. Further, we did not include patients who had an HbA1c of >53mmol/mol and were not taking any glucose-lowering therapies for legitimate reasons. Thus, further work is required to evaluate the uptake and use of this drug in patients who meet the clinical threshold for use.

Secondly, our study involved only those patients dispensed two or more medications during the study period—that is, patients indicated as already accessing and/or engaging with primary healthcare. Our dataset excluded 1,118 patients who did not meet this criterion, but we do not know the reasons behind why patients had <2 dispensings (eg, it was not clinically indicated, the patient was newly diagnosed and/or the patient had not visited their GP). This warrants further investigation, as at least some of these patients would likely benefit from the use of glucose-lowering therapies.

Our study was also restricted to only those practices in the Waikato region affiliated with two specific PHOs; we had no information about whether patients had moved out of region or changed PHOs during the study period. The inclusion of additional practices, particularly those from the National Hauora Coalition (NHC; the third PHO in the Waikato region) may have altered our findings because of the inclusion of Māori-led healthcare providers. As nearly a third of all patients who initiated vildagliptin in our study were Māori, we suggest that our study was not skewed by a lack of inclusion of NHC patient data. However, we do acknowledge that the Māori-led healthcare providers may have been more proactive at prescribing medication to Māori patients, and where possible these data should be included in future evaluations.

Fourth, our patient cohort was also largely defined using primary care read codes, which can be inaccurate. It is possible that the accuracy of these data may be different for different patient groups (eg, by ethnicity, VLCA status, etc) and the reliability of using read codes to define patient diagnoses should be validated before larger studies are undertaken.

Fifth, although our results preliminarily suggest that dispensing of vildagliptin is not reduced in Pacific patients compared to European, we must note that our cohort study was not powered appropriately to assess this outcome. As such, we suggest that further studies comprising larger numbers of Pacific type 2 diabetes patients are warranted. And lastly, it is possible that practice-level factors (eg, nurse-led clinics and/or onsite pharmacists) might influence the usage and uptake of new agents. This too should be evaluated in future studies.

In conclusion, there appears to be inequity in the initial uptake and use of open access vildagliptin in the Waikato region.

Authorship credit

LC, RL, RK and RP all contributed to the conception and design of the study, as well as interpretation of data. LC collected the data and CM analysed it. LC, CM, RP and RL drafted the article for publication. All authors revised it for critically important intellectual content. All authors give their approval for publication.

Summary

Abstract

Aim

To determine what the variation was in the initial use of vildagliptin in patients with type 2 diabetes following approval of open access funding in October 2018, including by ethnicity, gender, age, funding model and patient HbA1c levels.

Method

Data were collected from 31 general practices for all adult patients with type 2 diabetes. National Health Index-matched medication data were obtained from the national Pharmaceutical Collection. Patients were included for analysis if they had received at least one diabetes medication in the 12 months prior to funding approval for vildagliptin. The proportion of patients who initiated vildagliptin therapy following open access funding approval was then evaluated, as was the time taken until the first dispensing (days since funding approval).

Results

A total of 724 of 3,971 (18.2%) of patients initiated vildagliptin therapy; mean time to first dispensing was 192.1±112.4 days. In logistic regression, Asian patients were more likely and Māori less likely to receive vildagliptin than Europeans. Younger patients and those with an HbA1c of >64mmol/mol were also more likely to initiate therapy. Vildagliptin use by general practice ranged from 0.0–82.4%.

Conclusion

Despite open access funding, there was inequity in the initial use of vildagliptin. Substantial variation by general practice indicates that practitioner education may be needed to ensure appropriate and early adoption of new diabetes medications.

Author Information

Lynne Chepulis: Medical Research Centre, University of Waikato, Hamilton. Christopher Mayo: Faculty of Medical and Health Sciences, University of Auckland, Auckland. Ryan Paul: Medical Research Centre, University of Waikato, Hamilton; Waikato District Health Board, Hamilton. Rawiri Keenan: Medical Research Centre, University of Waikato, Hamilton. Ross Lawrenson: Medical Research Centre, University of Waikato, Hamilton; Waikato District Health Board, Hamilton.

Acknowledgements

We would like to thank the New Zealand College of General Practitioners for funding this study.

Correspondence

Lynne Chepulis, Waikato Medical Research Centre, University of Waikato, Private Bag 3105, Hamilton, New Zealand; +64 7 8384193

Correspondence Email

lynnec@waikato.ac.nz

Competing Interests

Nil.

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41. Curtis HJ, Dennis JM, Shields BM, Walker AJ, Bacon S, Hattersley AT, et al. Time trends and geographical variation in prescribing of drugs for diabetes in England from 1998 to 2017. Diabetes, Obesity and Metabolism. 2018;20(9):2159-68.

42. Sharma M, Nazareth I, Petersen I. Trends in incidence, prevalence and prescribing in type 2 diabetes mellitus between 2000 and 2013 in primary care: a retrospective cohort study. BMJ open. 2016;6(1).

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44. Lugtenberg M, Zegers-van Schaick JM, Westert GP, Burgers JS. Why don't physicians adhere to guideline recommendations in practice? An analysis of barriers among Dutch general practitioners. Implementation Science. 2009;4(1):54.

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47. Best Practice Advocacy Centre New Zealand. A rising tide of type 2 diabetes in younger people: what can primary care do? [Internet]. 2019 [cited 2019 Aug]. Available from: https://bpac.org.nz/2018/diabetes.aspx

48. Paul R. Type 2 Diabetes management guidelines: 2021 recommendations from NZSSD [Internet]. 2021 [cited 2021 Jun]. Available from: http://t2dm.nzssd.org.nz

49. Pharmaceutical Management Agency (Pharmac). PHARMAC to fund new diabetes medicines with amended Special Authority criteria [Internet]. 2021 [cited 2021 Jul]. Available from: pharmac.govt.nz

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Diabetes currently affects more than 260,000 people in New Zealand, including a disproportionate number of Māori and Pacific people, with disease prevalence increasing year on year.[[1]] Approximately 90–95% of these cases are type 2 diabetes, a disease characterised by insulin resistance and insulin deficiency[[2]] and due, in part, to reduced activity of incretin hormones.[[3]] Importantly, poorly controlled type 2 diabetes is associated with significant micro- and macro-vascular damage such that cardiovascular disease is the greatest cause of mortality in this population.[[2]]

Treatment of type 2 diabetes requires a multifaceted approach, including diet, exercise and medication.[[4,5]] The goal of therapy is to lower glycated haemoglobin (HbA1c) levels to generally less than 53mmol/mol (or, where indicated, to an alternative target)[[6,7]] and to reduce cardiovascular and renal risk factors.[[8]] However, management of type 2 diabetes is often suboptimal, with recent data from the Waikato region suggesting that 60% and 32% of patients had an HbA1c value of greater than 53mmol/mol and 64mmol/mol, respectively.[[9]] Similarly, only a third of patients with type 2 diabetes were shown to have blood pressure and/or lipids at or below clinically recommended targets, and up to three quarters of all patients were obese, with a body mass index >30kg/m[[2]].[[9]] Concerningly, it was also shown that there was considerable ethnic inequity in diabetes outcomes, with Māori patients being significantly more likely to have elevated HbA1c[[9–11]] and a greater prevalence of end-stage renal disease, diabetic eye disease, amputation and cardiovascular disease.[[12–15]] Not only does this lead to increased healthcare costs,[[16]] but more importantly an ongoing reduced quality of life for these patients.

Where lifestyle management is insufficient to manage type 2 diabetes, glycaemic control is typically achieved through a stepwise escalation of glucose-lowering therapies.[[17]] Metformin is the usual first-line oral glycaemic agent, with additional agents being added as required.[[5,18]] Vildagliptin, a dipeptidyl peptidase IV inhibitor (DPPIVi) that lowers glucose levels by increasing the activity of endogenous incretins, was added to the funding schedule in New Zealand in October 2018.[[18]] Prior to the long-awaited introduction of sodium-glucose transport protein 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) this year, vildagliptin was the preferred second-line funded agent for patients with type 2 diabetes in New Zealand, as, unlike sulphonylureas, insulin and pioglitazone, it does not cause weight gain or hypoglycaemia. Moreover, vildagliptin is the only currently known agent that can delay the need for insulin therapy when taken in combination with metformin,[[22]] and it has been shown to be a suitable glucose-lowering agent in patients with impaired renal function[[23]] or established cardiovascular disease.[[24]]

However, unlike SGLT2i and GLP1RA, no randomised controlled trials have demonstrated that DPPIVi reduces weight or cardiovascular events, such as myocardial infarctions or strokes. As such, SGLT2i and GLP1RA are now the preferred second-line agents for high-risk patients with type 2 diabetes, though PHARMAC has restricted the use of these medications under special authority, including an ethnicity clause to increase the uptake in Māori and Pacific peoples, which has resulted in significant debate.[[25,26]] In particular, it is unknown whether needing to obtain special authority approval may increase disparities by adding a further barrier for those who already have reduced access to optimal medications in primary care.[[ 26]] Importantly, the impact of a special authority versus open access on medication use has never been explored in a New Zealand context, and the degree of variability seen with open access diabetes medications is largely unknown. Thus, the aim of this study was to determine the variability in open access vildagliptin use in patients with type 2 diabetes in the Waikato region. This was explored by evaluating the initial uptake and usage of vildagliptin (following funding approval in October 2018), including by patient age, gender, ethnicity and/or the affordability of access to primary care (ie, whether a practice was Very Low Cost Access (VLCA) or not).

Methods

Study design

This sub-study was part of a larger project assessing the quality of diabetes care in primary care in New Zealand (including diabetes medication prescribing and dispensing). The aim of this specific study was to characterise the initial use of vildagliptin in patients with type 2 diabetes in the 14-month period following PHARMAC’s approval of open access funding (October 2018). Ethics approval was granted by the New Zealand Health and Disability Ethics Committee (ref: 19/CEN/8).

Data sources

Primary care data were sourced directly from Hauraki Primary Healthcare Organisation (PHO; 17 practices), and then additionally from the electronic patient management systems of 14 general practices affiliated with Pinnacle PHO during September–December 2020.

National Health Index (NHI)-identified patient information was extracted for all patients who had a confirmed diagnosis (≥12 months) of diabetes (read code C10 (diabetes mellitus)) and were aged ≥18 years on 1 October 2017. Extracted data included age (at time of data collection), gender, ethnicity and HbA1c levels (1 October 2017–30 September 2018). Patient records were also checked against the Waikato District Health Board (WDHB) clinical records to retrieve missing demographic and diagnosis information and to exclude patients with confirmed type 1 diabetes. The latter were identified from the clinical register of the WDHB Regional Diabetes Service, where all had their disease confirmed by an endocrinologist as per standard international criteria. Additional NHI-matched HbA1c data were obtained from Pathlab New Zealand for the same time-period, and these were combined and then averaged to provide a mean value for each patient for the study period, which was then used for all analyses. Ethnicity was coded as Level 1 data as collated from the primary care and/or WDHB datasets, with prioritisation to manage multiple ethnicities.[[27]]

NHI-matched medication dispensing data were obtained from the Ministry of Health’s Pharmaceutical Collection database (1 October 2017–31 December 2019). This included the 12-month “pre-funding period” (to exclude any patients who were already receiving unfunded vildagliptin) and the 14-month “post-funding period” (to ascertain who had initiated vildagliptin therapy). An additional two months were included in the post-funding period to allow for any initial delays in general practitioner (GP) awareness of the new funding guidelines.[[28]]

Data processing

For inclusion in the data analysis, patients with type 2 diabetes had to have been dispensed a glucose-lowering therapy (oral hypoglycaemic agents and/or insulin) at least twice during the pre-funding period. This ensured that the dataset only included patients who were being actively treated with medication. Patients were then excluded from this sub-group if they had died between 1 October 2018 and 31 December 2019 (n=46), or if they had been dispensed unfunded vildagliptin at least once during the pre-funding period (n=14).

General practices were coded as “VLCA” or “non-VCLA” based on their published patient fee structures. HbA1c levels were categorised as <53mmol/mol (current glycaemic target),[[6,7]] 53–64mmol/mol (previous Ministry of Health target)[[8, 10]] and >64mmol/mol.

Statistical analyses

Initially, the type 2 diabetes cohort was characterised for the 12-month pre-funding period, including by gender, age group, ethnicity, VLCA status and diabetes medication regimen. Initial vildagliptin use during the 14-month post-funding period (October 2018–December 2019) was then similarly described. The date of the first vildagliptin dispensing was recorded for each patient, and the cumulative uptake of vildagliptin (time to first dispensing) were plotted in a series of cox-regression plots by age, gender, VLCA status, ethnicity, medication adherence and HbA1c levels. Subgroup differences were analysed with chi-squared test, student t-tests and Mann-Whitney U tests.

A cross-sectional logistic regression adjusted for gender, age, ethnicity, rurality, VLCA and diabetes treatment regimen was used to estimate the odds ratio of a patient being dispensed vildagliptin during the post-funding period.

All data analyses were performed in Python 3.7 using the Pandas 0.25.3, Scipy 1.3.2 and Statsmodels 0.10.2 libraries with significance accepted at P<0.05.

Results

We identified a total of 4,031 patients with type 2 diabetes who had been dispensed diabetes medication ≥2 times during the pre-funding period. After excluding patient deaths (n=46) and unfunded-vildagliptin users (n=14), the final pre-funding study cohort consisted of 3,971 patients.

The demographics of the pre-funding type 2 diabetes cohort (n=3,971) are shown in Table 1, with the median age of participants being 64.5±12.8 years. Medication used included metformin monotherapy (37.4%), insulin (alone or in combination; 31.7%) and/or medication combinations. The mean HbA1c was 64.4±18.1mmol/mol, with 40% of patients having an HbA1c of >64mmol/mol (Table 1).

Table 1: Characteristics of the type 2 diabetes study population prior to vildagliptin funding (n=3,971) and then for those patients who initiated therapy after October 2018 (n=724). View Table 1.

Use of vildagliptin during the 14-month post-funding approval

A total of 724/3,971 patients (18.2%) were dispensed vildagliptin at least once in the 14-month post-funding period (October 2018–December 2019). The mean HbA1c of these patients was 72.5±18.2mmol/mol compared to 62.6±17.6mmol/mol in those who did not initiate therapy (P<0.001). The characteristics of patients who started vildagliptin therapy are given in Table 1. Vildagliptin users were more likely to be younger, Asian or Pacific and have a higher HbA1c level (all P<0.001). Patients on more than one diabetes medication were more likely to be prescribed vildagliptin than patients on one medication (62.9% vs 45.8%, p<0.001), and there was no difference in use with regard to gender or the VLCA status of the practice. Overall, 79 of the 724 patients who initiated vildagliptin (12.2%) had a mean study HbA1c of <53mmol/mol, including 20 Asian (19.1%), 42 European (14.6%), nine Māori (5.0%), four Pacific (6.7%) and four Other (30.8%).

Initiation of vildagliptin therapy also varied considerably between general practices (Figure 1). The total proportion of type 2 diabetes patients within each practice who were dispensed vildagliptin at least once ranged from 0.0% to 82.4%. A small number of practices were shown to initiate vildagliptin therapy in a large proportion of patients, and four practices did not add vildagliptin to therapy at all (Figure 1).

Figure 1: Proportion of type 2 diabetes patients within each practice initiating vildagliptin therapy (October 2018–December 2019; blue bars) and mean time to initiation (orange line). Note that practices 28–31 had zero patients commencing vildagliptin therapy.

As shown in Table 2, logistic regression with adjustment for age, gender, medication regimen, VLCA status and HbA1c level showed that there was no difference in initiation of vildagliptin therapy between European, Pacific or other ethnic groups, though vildagliptin was less likely to be dispensed to Māori patients (OR 0.67, 95% CI: 0.53–0.84; P=0.001) and more likely to be dispensed to Asian patients (OR 1.34, 95% CI: 1.02–1.78; p=0.039). Similarly, vildagliptin was less likely to be dispensed to those aged >74 years (OR 0.69, 95% CI: 0.52–0.90; P=0.007), those with an HbA1c of <64mmol/mol and those receiving insulin (OR 0.64, 95% CI: 0.43–0.99; P=0.043; Table 2). However, younger patients were more likely to have vildagliptin added to therapy, as were patients on combination therapy (metformin plus sulfonylureas) compared to those dispensed metformin monotherapy.

Table 2: Odds ratio (with 95% confidence intervals)[[1]] of patients initiating vildagliptin therapy. View Table 2.

Cumulative uptake of vildagliptin (time to first dispensing)

The overall, unadjusted cumulative uptake of vildagliptin after October 2018 by ethnicity, VLCA status and HbA1c band is shown in Figure 2. Māori and European patients had a comparable uptake of vildagliptin during the 14-month post-funding period (P=0.08), and uptake for both was lower than for Asian, Pacific and other ethnic groups. VLCA practices were faster to initiate vildagliptin therapy (P=0.02), but the proportion of patients using the medication in VLCA and non-VLCA practices was comparable by December 2020 (approximately 400 days). Initiation of vildagliptin therapy did not differ between males and females but was slower in older patients (P<0.05). As expected, vildagliptin uptake was highest in those with an HbA1c of >64mmol/mol (P<0.01; Figure 1).

Figure 2: Mean time to first dispensing (with 95% confidence intervals) of vildagliptin following PHARMAC’s approval of open access funding in October 2018 (A) by ethnicity, (B) by VLCA status and (C) by HbA1c group (mmol/mol). View Figure 2.

The mean overall time to first vildagliptin dispensing was 192.1±112.4 days, and nine of the 31 general practices (29%) had a mean time to vildagliptin use of less than 192.1 days (Table 2).

Discussion

Our study shows that initiation and/or early use of vildagliptin was associated with inequity in patients with type 2 diabetes in the Waikato region, with Māori being less likely to receive the medication after adjustment for age, gender, HbA1c level and VLCA status. This agrees with other studies that have shown that Māori are less likely to be dispensed oral diabetes medications,[[29–31]] with many researchers suggesting that this is due to Māori being less engaged with primary care.[[32,33]] The barriers for Māori accessing primary care (and healthcare in general) are well recognised in New Zealand,[[34–36]] and a recent report shows that access to medications has not improved for Māori in recent years.[[37]] It is clear that substantially more work is required to provide equitable access to health services in New Zealand.[[36,38]]

One way to improve access is by making primary care affordable for those in need.[[38]] For example, the VLCA scheme initiated in 2002 provides additional funding (and subsequently lower patient fees) to general practices where at least 50% of the enrolled patients are deemed “high needs”.[[39,40]] Indeed, we show that the mean time to the first dispensing of vildagliptin was lower in VLCA compared to non-VLCA practices, suggesting that that the lower costs associated with these practices may result in a faster uptake of new medications because of increased access to primary care (though there was no difference in the proportion of patients initiating therapy after 12 months). However, our study also showed that the VLCA status of the practice did not influence the proportion of patients with type 2 diabetes who initiated vildagliptin therapy during the 14-month post-funding period. Rather, we demonstrate that the practice (and therefore the GPs themselves) may be one of the most important factors that contribute to variability in initiation of therapy. Similarly, other studies have reported on the substantial variations seen in diabetes medication prescribing in primary care (particularly in the use of second-line medications),[[41,42]] and it has been suggested that this may be due to changes in, and/or lack of ease of use of, national policies and prescribing guidelines,[[42]] as well as differences in clinician-specific and environmental factors.[[43]]

Education has also been identified as a significant factor to consider when evaluating the initiation and update of newly approved medications. Primary care guidelines may change, for example, but doctors are often reluctant to immediately implement these changes; they cite reasons such as lack of evidence, organisational constraints, lack of knowledge about the guideline recommendations[[44]] and the uniqueness of individual cases as reasons.[[45]] Further, updated and/or new data are often not available via a central resource. Indeed, during the study period, the national guidelines on the management of type 2 diabetes were not updated to include vildagliptin,[[46]] and other resources, such as those published by the Best Practice Advocacy Centre (BPAC)[[47]] and the New Zealand Society for the Study of Diabetes,[[48]] may not have reached all prescribers.[[5,17,18,47]] Collectively, these issues cause discontinuity and variation in disease management, and this is congruent with our finding that the proportion of patients who initiated vildagliptin by practice varied from 0.0% to 82.4%.

Importantly, our study showed that, while the time to initiation of vildagliptin therapy was comparable for Māori and European, Māori were less likely to have vildagliptin dispensed. This has impact for the funding and access models used for the provision of other new medications in New Zealand: in particular, whether the ethnicity clause of the special authority criteria for SGLT2i and GLP1RA reduces the disparities in access to glucose-lowering therapies in Aotearoa New Zealand.[[49]] Although the full impact of the special authority criteria will not be known for some time, the data from the current study suggest that inter-practice variability in prescribing may be a significant contributor to medication use over and above whether a medication is available open access or via special authority, and it could be that GP education is required to increase new medication use for Māori patients.

Our study is the first to review the initiation and use of funded vildagliptin in a New Zealand population, though we do note the following study limitations. Firstly, we reviewed the use of vildagliptin without any assessment of whether the medication was clinically indicated. For inclusion in our study, patients with type 2 diabetes needed to have been receiving oral hypoglycaemic therapy, but it is possible that some of these had already met their individual clinical targets and thus did not require escalation of therapy. Indeed, 12.2% of those who initiated vildagliptin in our study had a most recent HbA1c of <53mmol/mol. Further, we did not include patients who had an HbA1c of >53mmol/mol and were not taking any glucose-lowering therapies for legitimate reasons. Thus, further work is required to evaluate the uptake and use of this drug in patients who meet the clinical threshold for use.

Secondly, our study involved only those patients dispensed two or more medications during the study period—that is, patients indicated as already accessing and/or engaging with primary healthcare. Our dataset excluded 1,118 patients who did not meet this criterion, but we do not know the reasons behind why patients had <2 dispensings (eg, it was not clinically indicated, the patient was newly diagnosed and/or the patient had not visited their GP). This warrants further investigation, as at least some of these patients would likely benefit from the use of glucose-lowering therapies.

Our study was also restricted to only those practices in the Waikato region affiliated with two specific PHOs; we had no information about whether patients had moved out of region or changed PHOs during the study period. The inclusion of additional practices, particularly those from the National Hauora Coalition (NHC; the third PHO in the Waikato region) may have altered our findings because of the inclusion of Māori-led healthcare providers. As nearly a third of all patients who initiated vildagliptin in our study were Māori, we suggest that our study was not skewed by a lack of inclusion of NHC patient data. However, we do acknowledge that the Māori-led healthcare providers may have been more proactive at prescribing medication to Māori patients, and where possible these data should be included in future evaluations.

Fourth, our patient cohort was also largely defined using primary care read codes, which can be inaccurate. It is possible that the accuracy of these data may be different for different patient groups (eg, by ethnicity, VLCA status, etc) and the reliability of using read codes to define patient diagnoses should be validated before larger studies are undertaken.

Fifth, although our results preliminarily suggest that dispensing of vildagliptin is not reduced in Pacific patients compared to European, we must note that our cohort study was not powered appropriately to assess this outcome. As such, we suggest that further studies comprising larger numbers of Pacific type 2 diabetes patients are warranted. And lastly, it is possible that practice-level factors (eg, nurse-led clinics and/or onsite pharmacists) might influence the usage and uptake of new agents. This too should be evaluated in future studies.

In conclusion, there appears to be inequity in the initial uptake and use of open access vildagliptin in the Waikato region.

Authorship credit

LC, RL, RK and RP all contributed to the conception and design of the study, as well as interpretation of data. LC collected the data and CM analysed it. LC, CM, RP and RL drafted the article for publication. All authors revised it for critically important intellectual content. All authors give their approval for publication.

Summary

Abstract

Aim

To determine what the variation was in the initial use of vildagliptin in patients with type 2 diabetes following approval of open access funding in October 2018, including by ethnicity, gender, age, funding model and patient HbA1c levels.

Method

Data were collected from 31 general practices for all adult patients with type 2 diabetes. National Health Index-matched medication data were obtained from the national Pharmaceutical Collection. Patients were included for analysis if they had received at least one diabetes medication in the 12 months prior to funding approval for vildagliptin. The proportion of patients who initiated vildagliptin therapy following open access funding approval was then evaluated, as was the time taken until the first dispensing (days since funding approval).

Results

A total of 724 of 3,971 (18.2%) of patients initiated vildagliptin therapy; mean time to first dispensing was 192.1±112.4 days. In logistic regression, Asian patients were more likely and Māori less likely to receive vildagliptin than Europeans. Younger patients and those with an HbA1c of >64mmol/mol were also more likely to initiate therapy. Vildagliptin use by general practice ranged from 0.0–82.4%.

Conclusion

Despite open access funding, there was inequity in the initial use of vildagliptin. Substantial variation by general practice indicates that practitioner education may be needed to ensure appropriate and early adoption of new diabetes medications.

Author Information

Lynne Chepulis: Medical Research Centre, University of Waikato, Hamilton. Christopher Mayo: Faculty of Medical and Health Sciences, University of Auckland, Auckland. Ryan Paul: Medical Research Centre, University of Waikato, Hamilton; Waikato District Health Board, Hamilton. Rawiri Keenan: Medical Research Centre, University of Waikato, Hamilton. Ross Lawrenson: Medical Research Centre, University of Waikato, Hamilton; Waikato District Health Board, Hamilton.

Acknowledgements

We would like to thank the New Zealand College of General Practitioners for funding this study.

Correspondence

Lynne Chepulis, Waikato Medical Research Centre, University of Waikato, Private Bag 3105, Hamilton, New Zealand; +64 7 8384193

Correspondence Email

lynnec@waikato.ac.nz

Competing Interests

Nil.

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