Physician-authored summaries and commentary on the most important medical research, provided by the NEJM Group, a division of the Massachusetts Medical Society.
© Massachusetts Medical SocietyAugust 2024
SGLT-2 inhibitors appeared to be more effective than sulfonylureas and DPP-4 inhibitors in an observational study.
Evidence to guide choices among the growing array of possible second-line treatments for patients with type 2 diabetes (who have inadequate control with metformin) remains limited. Most trials of available agents have been placebo-controlled, with few direct comparisons among available drug classes. Notably, researchers in the GRADE trial compared four second-line options directly but did not include sodium-glucose cotransporter-2 (SGLT-2) inhibitors (NEJM JW Gen Med Oct 15 2022 and N Engl J Med 2022; 387: 1063-1074, 1075-1088).
Researchers emulated a pragmatic randomised trial by using British national databases that contained information on 75,000 patients (mean age, 60 years) with diabetes who added SGLT-2 inhibitors, sulfonylureas or dipeptidyl peptidase-4 (DPP-4) inhibitors to metformin. At one and two years after treatment intensification, patients taking SGLT-2 inhibitors had significantly greater reductions in glycated haemoglobin (HbA1c) levels than did those taking DPP-4 inhibitors or sulfonylureas (0.3% greater decline in HbA1c after one year with SGLT-2 inhibitors vs both comparators). After two years, patients taking SGLT-2 inhibitors had lower risk for heart failure-related hospitalisations than did patients taking DPP-4 inhibitors or sulfonylureas (hazard ratios [HRs], 0.32 and 0.46, respectively) and lower risk for a 40% or greater decline in estimated glomerular filtration rate than did patients taking sulfonylureas (HR, 0.42).
Comment: Despite risk for residual confounding that is inherent in all observational studies, these findings suggest that SGLT-2 inhibitors, used as second-line treatment for patients with type 2 diabetes, might have greater metabolic and clinical benefits than do older oral agents. The investigators did not address possible harms of any of the three treatment classes and did not include glucagon-like peptide-1 (GLP-1) receptor agonists. Finally, although the hazard ratios noted above are impressive, absolute differences between the SGLT-2–inhibitor group and the other groups were small for cardiovascular and renal outcomes and probably would not be evident in younger populations.
Bruce Soloway, MD, Associate Professor Emeritus of Family and Social Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
Bidulka P, et al. Comparative effectiveness of second line oral antidiabetic treatments among people with type 2 diabetes mellitus: emulation of a target trial using routinely collected health data. BMJ 2024; 385: e077097.
This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine.