A comparative analysis of naïve basal insulin versus basal insulin plus sulfonylureas in patients with poorly controlled type 2 diabetes mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is a condition characterized by progressive pancreatic beta-cell dysfunction and insulin resistance. Despite lifestyle modifications and metformin treatment, T2DM often requires combination therapies, including insulin therapy. The mechanisms underlying the combination of insulin with sulfonylureas (SUs), typically referred to as bedtime insulin in conjunction with daytime SUs, are only partially understood. This study aims to clinically compare the effects of adding basal insulin to SUs versus twice-daily Neutral Protamine Hagedorn (NPH), focusing on the rationale underlying these results. A prospective cohort study was conducted at the Faiha Specialized Diabetes, Endocrine, and Metabolism Centre in Basrah (FDEMC), Iraq, from  May 2024 to April 2025. The study comprised 153 patients diagnosed with uncontrolled T2DM for a minimum duration of one year, all of whom were receiving the maximum doses of metformin and glimepiride. The participants were divided into two groups: the first group (n = 84) received an addition of bedtime NPH insulin, while in the second group (n = 69), SU was withdrawn and twice-daily NPH insulin was introduced. Both groups maintained the maximum tolerable doses of metformin throughout the study. Glycemic parameters and additional anthropometric and biochemical measurements were evaluated at baseline and the three-month follow-up. Baseline characteristics were comparable between the two groups. After three months, both treatment groups demonstrated similar improvements in glycemic control, with a mean HbA1c of 9.3±1.8% in the SU group and 9.3±2.2% in the non-SU group (p=0.909). Patients in the non-SU group exhibited more favourable glycemic excursions (65.9±44.9 mg/dL vs 92.8±53.8 mg/dL, p=0.052), indicating a potentially distinct mechanistic regulation of glucose homeostasis by the two therapeutic approaches. Additionally, there were relatively few variations in excursions between the two time frames observed in the non-Su group (p=0.025). Female patients and obese patients within the non-sulfonylurea group exhibited statistically significant reductions in blood glucose excursions by the end of the study (p = 0.028 and p = 0.022, respectively). This study demonstrates that SU and non-SU treatments yield similar overall glycemic control, with equivalent reductions in HbA1c levels at three months. However, non-SU treatment showed significant benefits, particularly in glycemic excursions, indicating different mechanisms influencing glucose homeostasis. A notable relationship was found between glycemic variability and non-SU treatment, especially in female and obese patients. These findings highlight the need for personalized treatment strategies, particularly with non-SU medications for specific patient subpopulations. Future research should include larger, randomized controlled trials to clarify the clinical implications and mechanisms of these treatments.