medwireNews: Second-line therapy choices for people with type 2 diabetes vary widely throughout the world and are influenced not only by clinical characteristics but also non-medical factors such as affordability and availability, results from the DISCOVER study show.
The study included data for 14,668 people with type 2 diabetes (53.9% men, mean age 57.5 years) from 37 countries across six World Health Organization global regions.
Overall, 80.7% of participants received metformin either alone or in combination as a first-line therapy.
The mean time from diagnosis to initiation of second-line therapy was 5.7 years, at which point the most common treatments were metformin in combination with other agents, typically dipeptidyl peptidase (DPP)-4 inhibitors (25.1%) or sulfonylureas (21.3%).
Just 4.3% received a sodium–glucose cotransporter (SGLT)-2 inhibitor and 1.3% received a glucagon-like peptide (GLP)-1 receptor agonist, both in combination with metformin, at second line. A further 6.2% were prescribed second-line insulin either alone or in combination with other therapies.
Among the 8488 patients prescribed first‐line metformin monotherapy, second-line treatment choices varied by region: sulfonylureas combined with metformin were the most common choice in Africa (63.6%), the Americas (34.2%), and South-East Asia (41.2%), whereas a DPP-4 inhibitor plus metformin was the most common choice in Europe (34.9%), the Eastern Mediterranean region (51.3%), and the Western Pacific region (41.3%).
Physicians from all regions cited expected efficacy as the most common reason for second-line treatment choice (cited by 43.4–88.6%). In addition, access, convenience, and cost were common reasons for choosing a second-line therapy in Africa (17.4%, 14.0% and 11.8%, respectively), whereas tolerability, weight, and hypoglycemia often affected treatment choice in Europe (28.9%, 28.9% and 26.9%, respectively).
Multivariate analyses showed that a number of both clinical and non‐medical factors were significantly associated with choice of second‐line therapy after metformin monotherapy.
For example, lower education level was associated with an increased likelihood for receiving sulfonylureas relative to DPP-4 or SGLT-2 inhibitors and GLP-1 receptor agonists, at odds ratios ranging from 0.17 to 0.70, depending on the drug and the number of years in education.
Antonio Nicolucci (Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy) and co-investigators say that this finding “may reflect lower socio-economic status and fewer economic resources of these people, leading to the prescription of more affordable drugs.”
Individuals with a glycated hemoglobin level of 9.0% or higher were more likely to receive insulin than a sulfonylurea, but were also more likely to receive a sulfonylurea than a DPP-4 or SGLT-2 inhibitor in addition to metformin.
In all regions, compared with Europe, treatment with a sulfonylurea in combination with metformin was more common than metformin plus an SGLT-2 inhibitor, GLP-1 receptor agonist, or insulin.
“This is likely to reflect the relatively high cost and low availability of these agents in some low- and medium-income countries compared with [sulfonylureas],” Nicolucci and team remark.
The researchers conclude in Diabetes, Obesity & Metabolism that “[t]ogether, these results suggest that many patients in large parts of the world are prescribed [sulfonylureas] rather than newer agents, such as DPP-4 inhibitors, SGLT-2 inhibitors or GLP-1 receptor agonists, when initiating second-line therapy, for economic and other non-medical reasons.
“This a real concern because these newer drugs are likely to have a better cardiovascular safety profile than [sulfonylureas],” they add.
By Laura Cowen
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Diabetes Obes Metab 2019; doi:10.1111/dom.13830