Type 2 diabetes

Sulphonylureas no longer favoured as second line therapy in T2D

Second line therapy for patients with type 2 diabetes should favour newer agents over addition of a sulphonylurea to metformin, an observational study suggests.

In a three year follow-up of patients with T2D initiating second‐line glucose‐lowering therapy, metformin in combination with a DPP‐4 inhibitor, an SGLT‐2 inhibitor or a GLP‐1 receptor agonist showed significant benefits at second line in comparison with metformin and a sulphonylurea.

Although reductions in HbA1c were similar across all four second‐line therapies, combinations of metformin with a sulphonylurea were associated with the lowest weight reduction, highest risk of hypoglycaemia and lower health-related quality of life compared to the other agents.

The findings, from a the DISCOVER study sponsored by AstraZeneca, suggested that sulphonylylureas should only be recommended as second-line therapy if cost or availability were issues, the study authors said.

The multinational study followed up 7613 patients with T2D who started on second line therapy with either a sulphonylurea (40.9%), DPP‐4 inhibitor (48.3%), SGLT‐2 inhibitor (8.3%) or a GLP‐1 receptor agonist (2.4%).

After three years, patients showed similar reductions in HbA1c of 0.8%‐1.0% with all therapy combinations.  However, those who received metformin plus a DPP‐4 inhibitor, an SGLT‐2 inhibitor or a GLP‐1 receptor agonist had greater weight loss (1.9, 2.9 and 5.0 kg, respectively) than patients who had a sulphonylurea with metformin  (1.3 kg, P < .0001).

Proportions of further treatment intensification were similar across combinations (19.9%‐26.2%).

The number of patients experiencing one or more hypoglycaemic events was also higher for metformin and sulphonylurea therapy  (11.9%) than other metformin combinations (3.9%‐6.4%, P < .0001).

At three years, the physical and mental health components of quality of life, as measured by SF‐36v2 summary scores, were significantly higher for patients treated with a DPP‐4 inhibitor or an SGLT‐2 inhibitor compared to those receiving metformin and sulphonylurea.

The study investigators said the real‐world data supported recent updates to guidance for management of type 2 diabetes that favoured newer agents such as SGLT‐2 inhibitors as the preferred second line treatments over sulphonylureas for most patients where cost was not an issue.

The Australian Diabetes Society recently updated its position statement on the Australian Type 2 Diabetes Glycaemic Management Algorithm, with the guidance favouring SGLT-2 inhibitors, DPP-4 inhibitor and GLP-1RA as the “usual therapeutic strategy” for second-line therapy, with sulphonylureas regarded as an “alternate approach”.

Previous guidance had included sulphonylureas as a usual therapeutic strategy.

“Choice of dual therapy should be guided by clinical considerations (presence of, or high risk of, cardiovascular disease, heart failure, chronic kidney disease, hypoglycaemia risk, obesity), side effect profile, contraindications and cost,” the algorithm advises.

The findings are published in Diabetes Obesity and Metabolism.

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