Two-Year Therapeutic Efficacy and Safety of Initial Triple Combination of Metformin, Sitagliptin, and Empagliflozin in Drug-Naïve Type 2 Diabetes Mellitus Patients (Diabetes Metab J 2024;48:253-64)
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We extend our gratitude to the reviewer for her thoughtful and insightful comments on our research and its broader implications [1]. We also concur with Professor Lee’s perspective that triple combination therapy with metformin, sitagliptin, and empagliflozin represents a promising strategy for drug-naïve patients with type 2 diabetes mellitus. The current body of evidence indicates that this initial triple combination therapy yields more durable reductions in glycosylated hemoglobin (HbA1c) compared to therapies that solely lower glucose levels without addressing the underlying metabolic abnormalities. Furthermore, the treatment provides superior glycemic control relative to monotherapy or a stepwise approach, and it enhances insulin sensitivity and β-cell function in patients with newly diagnosed type 2 diabetes mellitus [1-5].
Additionally, we would like to take this opportunity to provide a detailed commentary on the use of insulin in our study. Insulin therapy was administered to six of 36 patients whose HbA1c level remained at or above 7.0% after 24 months. Notably, in these six patients, HbA1c level was not well-controlled, with values of 12.9%±1.6% at baseline, 9.0%±1.4% at 12 months, and 11.1%±2.3% at 24 months. Despite these elevated HbA1c level, these patients did not exhibit hyperglycemic symptoms such as polyuria, polydypsia, or weight loss. For example, body weight increased over the treatment period: 72.6±30.4 kg at baseline, 74.5±33.4 kg at 12 months, and 77.8±34.0 kg at 24 months. Conversely, for the 30 patients who did not require insulin therapy, HbA1c level was relatively well-controlled (10.6%±1.6% at baseline, 7.2%±0.8% at 12 months, and 8.0%±1.1% at 24 months). They also did not present hyperglycemic symptoms, with stable weight (73.4±17.3 kg at baseline, 72.0±16.4 kg at 12 months, and 73.4±15.4 kg at 24 months) and no reports of polydipsia or polyuria.
We acknowledge the limitations of our study, as highlighted by our colleagues. Our research lacks a comparative arm with traditional sequential therapy or other combination therapies, and the potential for bias in subgroup analyses cannot be fully excluded. Additionally, the study population consisted exclusively of Korean patients from a single hospital, which may limit the generalizability of our findings. Nevertheless, there is a growing consensus on the superiority of triple combination therapy over stepwise therapy for achieving long-term durable glycemic control [2-5]. To solidify the role of this initial triple combination therapy as a viable strategy for drug-naïve patients with type 2 diabetes mellitus, we hope that future large-scale prospective studies will further validate the long-term efficacy and safety of this approach.
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CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.