Efficacy of Simplifying Complex Insulin Regimen on Glycometabolic Parameters and Target Organ Damage in Type 2...

Background: Fixed-ratio combinations (FRCs) provide an alternative to intensified conservative insulin treatments (ICTs); however, therapy simplification in patients with high total daily insulin dose (TDD) or high HbA_1c is a debated issue; additionally, its influence on target organ damage (TOD) is less known. Methods: Data were retrospectively collected from patients with Type 2 diabetes, including 58 patients who continued ICT and 104 patients who underwent therapy simplification between January 1, 2017, and January 1, 2023. Patient characteristics and therapy details are at baseline and 3, 6, 12, and 24 months after FRC initiation. Results: HbA_1c significantly decreased in both groups (-0.9% [-1.6%, -0.5%] with ICT vs. -1.3% [-2.1%, -0.3%] with FRC), whereas body weight significantly decreased only after simplification (-1 kg [-4, 1] vs. -5 kg [-7, -2]). Diabetes duration was not associated with therapy efficacy. Significant HbA_1c reduction and FRC dose elevation occurred earlier in patients with an initial HbA_1c > 8.0% than in those with an initial HbA_1c < 8.0%. FRC dose was significantly higher at 3 months in patients with a TDD of > 60 U/day than in those with lower TDD. Relative risk reduction with therapy simplification was 72.1%, 50.6%, 32.3%, and 59.7% for hypoglycemia, renal function decline, microalbuminuria, and macrovascular complications, respectively. Risk of retinopathy, neuropathy, and chronic kidney disease did not significantly change with FRCs. Discussion: FRCs are safe and as effective as ICT even in patients with high initial HbA_1c, high TDD, or long diabetes duration. A protective role of FRCs in diabetic ASCVD has been proven, but their protective role in CKD was not observed. Conclusions: The significant improvements in glycemic and weight control, as well as in TODs, suggest that therapy simplification may represent a more favorable approach compared to the continuation of previous ICT even in patients characterized by high baseline TDD and HbA_1c levels.