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. 2025 Nov 1.
doi: 10.1007/s12325-025-03394-2. Online ahead of print.

ADD2Dia: Real-World Clinical Effectiveness of Adding a Sodium-Glucose Cotransporter 2 Inhibitor to Gliclazide-Based Therapy in Type 2 Diabetes

Rodrigo O Moreira  1   2 , Nemencio A Nicodemus Jr  3 , Abdurrahman Comlekci  4 , Miao Yu  5 , Mussa H Almalki  6   7
Affiliations

ADD2Dia: Real-World Clinical Effectiveness of Adding a Sodium-Glucose Cotransporter 2 Inhibitor to Gliclazide-Based Therapy in Type 2 Diabetes

Rodrigo O Moreira et al. Adv Ther. .

Abstract

Introduction: This study investigated the real-world clinical effectiveness and tolerability of adding a sodium-glucose cotransporter 2 inhibitor (SGLT2i) to gliclazide modified release (MR)-based therapy in a sample of patients with type 2 diabetes (T2D) across five countries, and its value as an effective and well-tolerated strategy in T2D management in a diverse patient population, including those at high risk.

Methods: This non-interventional, retrospective chart review study included patients with T2D treated with gliclazide MR-based therapy and an SGLT2i for at least 60 days. The primary outcome was change in glycated hemoglobin (HbA1c) levels. Secondary outcomes included treatment patterns, proportion of patients achieving an HbA1c target < 7%, changes in lipid profile, blood pressure, weight, new-onset comorbidities, and adverse events of special interest (AESI).

Results: A total of 537 patients (47.7% female, mean age of 59.2 years, mean disease duration 10.0 years) were included, of whom 75.4% were obese/overweight and 15.1% had atherosclerotic cardiovascular disease (ASCVD). At baseline, HbA1c was uncontrolled (≥ 7%) in 87.2% of patients (mean HbA1c of 8.7% [SD 1.7]). Mean HbA1c reductions were - 1.1% (SD 1.8) at 6 months, - 0.7% (SD 1.9) at 2.4 years, and - 0.6% (SD 1.7) at 3 years. The proportion of patients with HbA1c < 7% increased from 12.8% at baseline to 29.3% at least once during follow-up. Mean body weight decreased by 1.7 kg (95% CI - 2.2, - 1.3). AESIs were reported in 40 patients (7.4%) with urinary tract infections being the most common (6.8%).

Conclusion: The first real-world study of the long-term combination of gliclazide MR and SGLT2i demonstrated its value as an effective and well-tolerated strategy in T2D management, particularly in high-risk populations. This combination provided clinically meaningful and sustained HbA1c reductions and improved cardiometabolic parameters in a diverse T2D population, with very few adverse events. These results align with current guidelines emphasizing the importance of early combination treatment and multifactorial risk management in T2D and highlight the need to address late treatment intensification indicative of clinical inertia.

Trial registration: ClinicalTrials.gov Identifier NCT06708091.

Keywords: Combination treatment; Gliclazide MR; HbA1c; Real-world; SGLT2i; Type 2 diabetes.

Plain language summary

A significant proportion of people with type 2 diabetes do not control their blood glucose (sugar) level despite taking medicines to reduce it. Poor glucose control increases the risk of heart, circulatory and kidney problems, and death. The ADD2Dia study investigated whether combining two diabetes medicines with different mechanisms would improve a key measure of glucose control called HbA1c in people with long-term, poorly controlled type 2 diabetes. The study was carried out in routine practice at 25 sites in five countries, so patients were typical of those doctors treat in their clinics. When patients added a sodium-glucose cotransporter inhibitor to the gliclazide modified release-based therapy they were already taking, there was a meaningful, early and long-term improvement in their glucose control, especially in those with highest HbA1c levels. The proportion of people who achieved the desired HbA1c target of less than 7% doubled from 12.8% at the start of the study to 29.3% at the end. There were also improvements in body weight, cholesterol, and blood pressure. Few adverse effects were reported, and rates of hypoglycemia (a potentially dangerous fall in glucose level) were low. The results are in line with current guidelines for doctors that stress the importance of early combination treatment for people with type 2 diabetes and the management of other risk factors for heart and circulatory diseases. They support the effectiveness and tolerability of gliclazide modified release and sodium-glucose cotransporter inhibitor in a wide range of people with poorly controlled type 2 diabetes.

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Conflict of interest statement

Declarations. Conflicts of Interest: Rodrigo Moreira: Fees as speaker from Servier, Novo Nordisk, AstraZeneca, Bayer, Eli Lilly. Nemencio A Nicodemus Jr.: Speaker honoraria from Servier, AstraZeneca, Boehringer Ingelheim and Taisho. Abdurrahman Comlekci: No conflict of interest. Miao Yu: Honoraria for speaker engagement from MSD, Novo Nordisk, Sanofi, Eli Lilly, Novartis, Servier and AstraZeneca; has served on Advisory boards for Novo Nordisk, Sanofi, MSD, Eli Lilly, Roche and AstraZeneca. Mussa H Almalki: No conflict of interest. Ethical Approval: The study was performed in accordance with the Helsinki Declaration of 1964, and its later amendments. Ethics approval was received from appropriate committees in each of the countries where the study was conducted, representing all the sites that were included (Supplementary Table 1). Informed consent for medical record review and the use of research-related health information was obtained in accordance with local regulations.

References

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