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SGLT2 Inhibitors vs. DPP-4 Inhibitors in Type 2 Diabetes & Effects of Baseline A1c Levels

Patients with type 2 diabetes (T2D) and elevated baseline hemoglobin A1c (HbA1c) levels benefit from sodium-glucose cotransporter 2 inhibitors (SGLT2i) treatment regardless of glycemic control, a study shows. No additional risk of adverse events occurred in those with higher HbA1c levels beyond the risk in patients started on dipeptidyl peptidase 4 inhibitors (DPP-4i) therapy. “Overall, patients receiving a SGLT2i had a 15% lower risk of the composite of myocardial infarction, stroke, or death from all causes (approximately 3 fewer cases per 1000 person-years) and a 54% lower risk of [hospitalization for heart failure (HHF)] (approximately 4 fewer cases per 1000 person-years) than those receiving a DPP-4i,” the authors write.

The new-user comparative effectiveness and safety research study relied on analysis of the records for 144,614 commercially insured adults with a diagnosis of T2D who initiated treatment with SGLT2i or DPP-4i and had at least 1 HbA1c laboratory result recorded within 3 months before treatment initiation. Based on the primary outcomes of a composite of myocardial infarction, stroke, or all-cause death (modified major adverse cardiovascular events [MACE]) and HHF, the researchers report these results: “A total of 144,614 eligible adults (mean [SD] age, 62 [12.4] years; 54% male participants) with T2D initiating treatment with a SGLT2i (n = 60,523) or a DPP-4i (n = 84,091) were identified; 44,099 had an HbA1c baseline value of less than 7.5%, 52,986 between 7.5% and 9%, and 47,529 greater than 9%. Overall, 87,274 eligible patients were 1:1 propensity score–matched: 24,052 with HbA1c less than 7.5%; 32,290 with HbA1c between 7.5% and 9%; and 30,932 with HbA1c greater than 9% (to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01). The initiation of SGLT2i vs DPP-4i was associated with a reduction in the risk of modified MACE ([incidence rate (IR) per 1000 person-years 17.13 vs 20.18, respectively; [hazard ratio (HR)], 0.85; 95% CI, 0.75-0.95; [rate difference] (RD)], −3.02; 95% CI, −5.23 to –0.80) and HHF (IR per 1000 person-years 3.68 vs 8.08, respectively; HR, 0.46; 95% CI, 0.35 to 0.57; RD −4.37; 95% CI, −5.62 to −3.12) over a mean follow-up of 8 months, with no evidence of treatment effect heterogeneity across the HbA1c levels. Treatment with SGLT2i showed an increased risk of genital infections and [diabetic ketoacidosis] and a reduced [acute kidney injury] risk compared with DPP-4i. Findings were consistent by HbA1c levels, except for a more pronounced risk of genital infections associated with SGLT2i for HbA1c levels of 7.5% to 9% (IR per 1000 person-years 68.5 vs 22.8, respectively; HR, 3.10; 95% CI, 2.68-3.58; RD, 46.22; 95% CI, 40.54-51.90).”

Source: JAMA Internal Medicine