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A worthwhile investment for people with type 2 diabetes

9th March 2023
A pile of white tablets

SGLT-2 inhibitors and GLP-1 receptor agonists have benefits that go beyond glucose-lowering in diabetes. A new study, reported in Diabetologia, looked at the cost-effectiveness of these medications. The findings may lead to more widespread use and could reduce heart and kidney complications for those living with type 2 diabetes. Dr Susan Aldridge reports.

Recent clinical trials have shown that SGLT-2 inhibitors and GLP-1 receptor agonists reduce the incidence of cardiovascular and kidney disease in people with type 2 diabetes, independently of their glucose-lowering effect. For instance, SGLT-2 inhibitors reduce hospitalisation for heart failure (HF) by 33% and end-stage kidney disease (ESKD) by 35%, while GLP-1 receptor agonists reduce myocardial infarction (MI) by 10% and stroke by 17%. SGLT-2 inhibitors have also been shown to reduce the incidence of cardiovascular and kidney disease in people without diabetes as well, suggesting that their use has benefit independent of HbA1c levels.

In light of this evidence, the recently updated American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) consensus guidelines for treatment of people with type 2 diabetes recommend the use of SGLT-2 inhibitors and GLP-1 receptor agonists for those with, or at risk of, cardiovascular and kidney disease. However, uptake of these medications, particularly the GLP-1 receptor agonists, among people with type 2 diabetes has been limited so far.

A crucial barrier is their high cost. Previous cost-effectiveness analyses of these medications have tended to focus on their glucose-lowering effect. To expand their use earlier in the course of diabetes, and irrespective of HbA1c, we really need to know how cost-effective they are in terms of their cardiovascular and kidney benefits.

Accordingly, Jedidiah Morton of Monash University, Australia, and colleagues, have constructed a model using a real-world population with type 2 diabetes to assess the cost-effectiveness of widespread use of SGLT-2 inhibitors and GLP-1 receptor agonists, considering only major cardiovascular and kidney outcomes.

Modelling the health economics of type 2 diabetes

The model used real-world, individual-level data capturing the probable incidence and costs of ESKD, non-fatal hospitalisations for MI, HF, stroke and all-cause mortality among people with type 2 diabetes in Australia from 2020 to 2040. This data came from the National Diabetes Services Scheme and national hospital and mortality data.

Baseline health states were assigned using data from 2010 to 2019 and the population was then ‘aged’ in yearly cycles, using probability data to track incidence of the above events (ESKD and so on) to build up the model. Additionally, a cohort of new-onset type 2 diabetes was added each year.

Outcomes were total probable cases of ESKD, hospitalisation for MI, HF and stroke, years of life lived, quality-adjusted life years (QALYs), healthcare costs and societal costs. The primary outcome was incremental cost-effectiveness ratio (ICER), which is the cost per QALY gained, with the willingness-to-pay threshold set at per QALY. Put simply, cost-effectiveness would be achieved if the ICER was less than or equal to $AU28,000.

Outcomes were evaluated in two different populations: the total population with type 2 diabetes and the secondary prevention population, which was everyone with type 2 diabetes who had prior cardiovascular disease (CVD) – either an actual admission from 2010 to 2019 or a modelled admission from 2020 to 2040 for MI, HF or stroke.

The researchers modelled four different scenarios. In the first two, the use of SGLT-2 inhibitors or GLP-1 receptor agonists was increased to 75% of the total type 2 diabetes. In the third and fourth scenarios, this increase was confined to the secondary prevention population. The four scenarios were compared with the use of these medications in 2019 – the last year for which data was available – which was around 20% for SGLT-2 inhibitors and 5% for GLP-1 receptor agonists. These figures were about the same for people with and without prior cardiovascular disease. The impact of the increased use of the two medications in the four scenarios was calculated using data from recent meta-analyses of major outcomes trials for SGLT-2 inhibitors and GLP-1 receptor agonists. 

Focus on cost-effectiveness

The prevalence of diabetes in Australia was projected to grow from 1.13 million in 2020 to 1.45 million in 2040. Compared with current use of 20% of SGLT-2 inhibitors, increasing their use to 75% in the total population with type 2 diabetes would result in a gain of 400,018 extra years of life and 176,446 QALYs, according to this model.

The corresponding ICER for healthcare costs would be AU$23,717, taking into account the cost of the medication and setting it against the healthcare cost reductions from having fewer diabetes complications. The secondary prevention population numbered 95,247 people and 75% SGLT-2 inhibitor use would lead to a gain of 29,357 QALYs and an ICER of AU$8878.

For GLP-1 receptor agonists, the corresponding figures for the whole type 2 diabetes population were 460,028 extra years of life and 200,932 QALYs. The ICER was calculated as $AU100,705, again taking into account a reduction in healthcare costs arising from wider use of these medications. For the secondary prevention population, GLP-1 receptor agonists used for 75% would lead to a gain of 36,090 QALYs and an ICER of AU$79,742.

These findings suggest that use of SGLT-2 inhibitors is probably cost-effective in both the total and secondary prevention populations. However, the analysis suggests that GLP-1 receptor agonists are not likely to be cost-effective from a healthcare or societal perspective at current prices. This has important policy implications, suggesting that reimbursement criteria that limit use of SGLT-2 inhibitors, where they exist, should perhaps be re-considered. Currently, too many people living with type 2 diabetes are missing out on the benefits of these medications, which this new study shows to be a worthwhile investment in their future health.

This is the first cost-effectiveness analysis of its kind. Other studies have excluded cardiovascular or kidney benefits or modelled the populations used in cardiovascular outcomes trials, which represent only 20 to 60% of people with type 2 diabetes. Most of those studies have also found SGLT-2 inhibitors to be cost-effective.

This new study extends these findings by showing cost-effectiveness of SGLT-2 inhibitors, regardless of their effects on glucose levels. This doesn’t mean everyone with type 2 should be on them, however, nor does this study address other considerations about their widespread use.

Interpretation of the findings on GLP-1 receptor agonists is more complex. If you look only at cardiovascular benefit, they are not cost-effective in either the total type 2 diabetes population or those with existing cardiovascular disease. However, GLP-1 receptor agonists lead to weight loss and have less risk of hypoglycaemia compared with sulphonylureas and insulin, and are very effective glucose-lowering medications. None of these benefits was considered in this study.

Further analyses taking a more detailed look at the GLP-1 receptor agonists’ cost-effectiveness are needed. This is important because there is already a high burden of CVD in type 2 diabetes and, with an ageing population, stroke in particular is becoming more common. These are outcomes that could be improved by an increased uptake of GLP-1 receptor agonists.

To read this paper, go to: Morton J, Marquina C, Shaw J, Lieu D, Polkinghorne K, Ademi Z, Magliano D. Projecting the incidence and costs of cardiovascular and kidney complications of type 2 diabetes with widespread SGLT2i and GLP-1 RA use: a cost-effectiveness analysis. Diabetologia online 21 November 2022.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.