A new study in Diabetologia finds that people with type 2 diabetes who are socioeconomically disadvantaged are less likely to be prescribed incretin-based therapies, including GLP-1 receptor agonists, even though they may have more to gain from such treatments. The authors suggest a number of ways of moving forward so that better value for money for society can be obtained from these new cardioprotective therapies. Dr Susan Aldridge reports.
Low socioeconomic status has a negative impact on morbidity and mortality and is also a risk factor for type 2 diabetes via mediators including obesity, alcohol, reduced physical activity, stress, low health literacy and limited access to healthy food and exercise facilities. The result is often poor diabetes management and increased risk of cardiovascular complications.
Disparities in care, including the unequal use of incretin-based therapies, are also influenced by socioeconomic status. The incretin-based therapies are glucose-lowering drugs, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 (DPP-4) inhibitors and the recently developed dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs, such as tirzepatide. The ADA and EASD recommend use of agents that have demonstrated cardiovascular benefit in those individuals with type 2 diabetes with cardiovascular risk. Certain GLP-1 RAs are included among these agents and emerging data suggests that tirzepatide, too, may have cardioprotective effects.
In a new review, Apostolos Tsapas and colleagues at Aristotle University of Thessaloniki, Greece, have summarised real-world evidence on the use of incretin-based therapies in clinical practice across the socioeconomic spectrum. They look at socioeconomic disparities in the adoption of these therapies, the possible factors driving these and how these might be addressed in the future. The study consisted of a literature search focusing on incretin-based therapy use with regard to the following aspects of socioeconomic status: area-level indexes, income, education, sociodemographic variables.
Area-level indexes and income
One study in the US showed that individuals with type 2 diabetes and cardiovascular disease with increased area-level socioeconomic deprivation were less likely to receive GLP-1 RAs compared with those living in more privileged areas. In Australia, the Index of Relative Socioeconomic Disadvantage ranks areas according to information on income, education, employment, occupation, housing and other indicators. A study assessing the relationship between use of incretin-based therapies and the Index found that those in the most disadvantaged areas were consistently less likely to receive GLP-1 RAs, while the opposite was so for DPP-4 inhibitors.
The study also found a connection between low socioeconomic status and a reduced probability of receiving SGLT-2 inhibitors, while no such relationship was observed for metformin, sulphonylureas or insulin. And, according to a UK study, when fully accounting for various confounding factors, those belonging to the most deprived group, as identified by the Index of Multiple Deprivation, had a lower likelihood of being prescribed GLP-1 RAs.
In another study from the US, the odds of being treated with a GLP-1 RA were greater among individuals with diabetes who had a high household income compared with those whose annual income was less than $50,000. Higher income individuals were also more likely to be on GLP-1 RAs in the All of Us Research Program, a US contemporary cohort study. Finally, in Denmark, metformin-treated patients with a high household income were more likely to initiate second-line treatment with a GLP-1 RA compared with those with a low household income.
Education and sociodemographic factors
Education is often used as an indicator of socioeconomic status because it captures the knowledge-related assets of a person and determines their future employment, occupation and income. In the US, those with a high-school education had lower odds of receiving a GLP-1 RA prescription in comparison with those who had a postgraduate degree. Similarly, in the All of Us Research Program, a higher percentage of those who went to college were on GLP-1 RAs compared with those with less than a high-school diploma. In Denmark, the probability of initiating a GLP-1 RA was higher in those with a college education compared with lower educational levels.
In addition, multinational data from the global DISCOVER programme suggested that those who had less than 13 years of education had lower odds of receiving a GLP-1 RA than a sulphonylurea. Similar, although less marked, associations with education level and drug utilisation were also found for DPP-4 inhibitors, but not for insulin.
Meanwhile, sociodemographic factors, such as race/ethnicity and age can also influence the uptake of newer medications. For instance, retrospective cohort data from the US suggest that, compared with White individuals with type 2 diabetes, Asian, Black and Hispanic individuals were less likely to receive GLP-1 RA therapy. In the UK, compared with White individuals, Asian and Black minorities were more likely to be prescribed metformin or sulphonylureas than GLP-1 RAs or SGLT-2 inhibitors. And in Denmark, inequalities in GLP-1 RA therapy between those with a high income and those with a low income were more pronounced in immigrants than the native Danish population. Finally, in the US, older age has been associated with a lower probability of receiving GLP-1 RAs or SGLT-2 inhibitors in those with type 2 diabetes and atherosclerotic cardiovascular disease.
Drivers of inequalities in incretin-based therapy
The authors have identified some key mechanisms that underlie the inequalities reported above. Firstly, people may simply not be able to afford incretin-based therapies and this will, of course, vary according to the country where they live. In a system that provides universal reimbursement, such as the UK and many other European countries, access to these therapies may be more equitable because the treatments are available to more of the population, regardless of their financial status. However, access to GLP-1 RAs is not consistent across European populations. For example, in the UK, they can only be prescribed to people with type 2 diabetes who also have obesity, while other countries do not impose such restrictions.
Where insurance coverage is not universal, as in the US, people with lower socioeconomic backgrounds may face barriers in accessing these therapies, due to higher out-of-pocket costs or limited insurance coverage. In the US, for instance, many states lack expanded Medicare coverage and one study has shown that even Medicare beneficiaries are less likely to receive GLP-1 RAs than those with private insurance. A similar trend has been uncovered in Germany, with private health insurance being a strong predictor of GLP-1 RA prescription.
The disparity in use of GLP-1 RAs according to income is currently being exacerbated by the current global shortage of semaglutide and dulaglutide, which is being driven, in part, by increasing off-label use for weight loss. So a considerable proportion of limited supply is being redirected towards well-off individuals seeking weight reduction, regardless of their diabetes status. This situation disproportionately affects those of lower socioeconomic status with type 2 diabetes and cardiovascular disease, who are totally dependent upon affordable reimbursement to access these medications.
Secondly, there is the issue of actual access to incretin-based therapies. People living in rural or disadvantaged areas may find it hard to get to an appointment with a diabetes specialist who is well-versed in these new drugs. Finding a pharmacy that stocks them may be another challenge. Primary care physicians may not be fully aware of the cardiovascular benefits of incretin-based therapies and may be reluctant to prescribe them, even to their patients with cardiovascular disease. And, of course, most people with type 2 diabetes are treated in primary care. Research has confirmed that diabetologists and endocrinologists are more likely to prescribe GLP-1 RAs, perhaps because they are more familiar with injectables.
Thirdly, disadvantaged groups have been consistently reported to have lower health literacy than more privileged groups in society and this has been associated with poorer health outcomes and decreased uptake of therapeutic and preventive interventions. Those with low health literacy may find it difficult to understand health information and communicate effectively with healthcare professionals.
In some countries, they may be confused about insurance coverage options and the availability and out-of-pocket costs of GLP-1 RAs. These concerns may lead them to avoid or postpone treatment. Furthermore, those with low health literacy are less likely to be well-informed about the cardiovascular benefits of GLP-1 RAs and might not feel confident in trying to access, or get a referral, to a diabetes specialist in order to get a prescription. And during a consultation with a healthcare provider, they may find it challenging to raise their concerns about cost or the need for subcutaneous administration. Language and cultural barriers may also arise.
Finally, on the other side of the consultation, there may be conscious or unconscious bias on the part of the healthcare provider. A recent study has shown that GLP-1 RAs are less likely to be prescribed to patients from lower socioeconomic backgrounds or minority groups, who are perceived to be less compliant to treatment and medical advice, or unable to afford the cost of these drugs.
Increasing societal benefit from incretin-based therapy
Reflecting on the above, the authors propose some strategies for increasing the uptake of incretin-based therapy. There are consistent data from clinical trials supporting the use of incretin-based therapies, particularly GLP-1 RAs, in socioeconomically disadvantaged people. They have much to gain as they are at increased risk of cardiovascular complications in type 2 diabetes and should therefore be a priority for receiving these treatments.
Addressing barriers to accessing incretin-based therapies is vital for increasing and widening their uptake. This might mean providing transportation to appointments for those living in rural or low-income regions and increasing the availability and retention of both primary care and specialist staff in underserved areas. Meanwhile, primary care physicians’ familiarity with GLP-1 RAs should be improved through targeted education, training and resources, given that most people with type 2 diabetes are treated in primary care.
The authors emphasise that the availability of beneficial medications at low cost is the key to increasing their value for money from a broader societal perspective. This is especially pertinent when it comes to considering the newer, high-cost incretin-based therapies such as semaglutide or tirzepatide.
A recent study from the US concluded that, as a first-line therapy, the cost of GLP-1 RAs needs to fall by at least 70% to be cost-effective in comparison with metformin. Another Australian study says that GLP-1 RAs are not cost-effective at current prices for either primary or secondary cardiovascular prevention – although SGLT-2 inhibitors are. Similar findings emerged from an analysis of data from 67 low- and middle-income countries. Finally, a review from high-income countries has suggested that GLP-1 RAs were not cost-effective compared with DPP-4 inhibitors, sulphonylureas or thiazolidinediones.
These economic evaluations highlight the need for country-specific strategies to improve the cost-effectiveness of GLP-1 RAs. These would include collaborative efforts between governments and pharmaceutical companies to lower drug prices, establish product listing agreements and promote generics. The authors note that the manufacturer of liraglutide and semaglutide has recently enjoyed a significant increase in market cap, reflecting its robust financial position. Thus, there is scope for negotiating lower prices for these medications without adversely impacting company profitability or scope for research and investment.
Improving health literacy in people with type 2 diabetes can help them appreciate the importance of preventing cardiovascular complications and help them actively participate in discussion with their physicians about potentially cardioprotective drugs. Through shared decision-making, patients may be more able to accept co-payments for these drugs and overcome barriers such as the need for injection with GLP-1 RAs. This collaborative approach can enhance treatment adherence and persistence, ultimately leading to better outcomes.
Finally, it is necessary to address physician-patient barriers. This can be a complex issue, requiring a multifaceted approach, including implicit bias training and promoting diversity within healthcare professions. The former helps healthcare professionals to become aware of any unconscious prejudice that might be affecting their decision-making and contributing to disparities in prescribing incretin-based therapies. The latter creates a more inclusive healthcare environment, which may help promote better understanding of those from disadvantaged groups.
The authors have highlighted disparities in the uptake of incretin-based therapies, particularly GLP-1 RAs, in people with type 2 diabetes according to socioeconomic status. An essential first step in addressing this problem is advocating for a reduction in the price of GLP-1 RAs, which would improve their value for money for society at large. This approach would complement other measures, such as increasing accessibility, improving health literacy and overcoming physician-patient barriers.
However, much of the evidence informing this paper comes from the US and findings may not be generalisable to other settings, so additional research on uptake disparities and context-specific strategies for improvement is needed. Collaborative efforts to implement these strategies will boost the societal outcomes of the incretin-based therapies and improve health outcomes for those with type 2 diabetes.
To read this paper, go to: Karagiannis T, Bekiari E, Tsapas A. Socioeconomic aspects of incretin-based therapy. Diabetologia 12 July 2023. https://doi.org/10.1007/s00125-023-05962-z
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Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.