Dapagliflozin and Sitagliptin FDC: Exploring Early Initiation Benefits In Young Newly Diagnosed T2D in India

Early intensive glycemic control from diagnosis is critical, conferring a lasting "legacy effect" that significantly reduces cardiovascular, renal, and all-cause mortality for decades. [3] Early selection of therapies with proven cardiovascular and renal benefits is vital, as young T2D patients likely have an early and prolonged duration of cardiorenal risk. [4] Preserving beta-cell function is the key to delaying disease progression; hence, early use of beta-cell independent therapies is particularly important in young-onset T2D, where beta-cell failure occurs earlier. [5]

Considering SGLT2i + DPP4i Early in Young T2D: Clinical Rationale

Type 2 diabetes involves progressive β-cell dysfunction and multiple underlying metabolic defects. Early combination therapy optimally targets these pathways simultaneously (Figure 1), achieving glycemic targets faster, circumventing clinical inertia, and potentially preserving β-cell function.

This combination of SGLT2i and DPP4i provides complementary beta-cell independent action, synergistically reducing both fasting and postprandial glucose. Together, they restore α- and β-cell function while offering cardiorenal protection advantages, particularly crucial for young patients requiring decades of durable gluco-metabolic control. [6]

Figure: Mechanisms of Dapagliflozin-Sitagliptin Combination Therapy. Adapted from Ravikumar L et al. Cardiol Cardiovasc Med. 2023;7:141-144.

SGLT-2, Sodium-Glucose Co-Transporter-2; DPP-4, Dipeptidyl Peptidase-4; GLP-1, Glucagon-Like Peptide-1; GIP, Glucose-Dependent Insulinotropic Polypeptide; SBP, Systolic Blood Pressure. ↑ indicates increase; ↓ indicates decrease.

Dapagliflozin & Sitagliptin FDC: Latest 2025 Indian Clinical Evidence

Dapagliflozin-Sitagliptin Benefits Young Indian T2D with Cardio-Metabolic Co-Morbidities: The recently published REALIZE Study (October 2025), a retrospective, real-world study of 250 young T2D patients (mean age of 46.9 years) with cardiometabolic comorbidities across five Indian sites, demonstrated significant multi-organ benefits over approximately 3-4 months. HbA1c decreased by 1.1% (8.4% to 7.4%), fasting glucose dropped 29.5 mg/dL (164.0 to 134.5 mg/dL), and postprandial glucose fell 36.8 mg/dL (226.3 to 189.5 mg/dL), all p<0.001. Among kidney function, eGFR increased by 5.3 mL/min/1.73m² (86.7 to 92.0 mL/min/1.73m²), serum creatinine decreased by 0.5 mg/dL (1.4 to 0.9 mg/dL), and uACR reduced by 76.5 mg/g (173.3 to 96.9 mg/g), all p<0.001. Blood pressure reduced significantly (systolic -5.9 mmHg, diastolic -2.3 mmHg, both p<0.001), weight decreased by 1.7 kg (p=0.004), and triglycerides lowered by 23.7 mg/dL (p=0.002). The study indicated the combination of dapagliflozin and sitagliptin led to significant improvements in glycemic, renal, and cardiovascular parameters in patients with T2D. [7]

Dapagliflozin Sitagliptin Provides Cardiorenal Protection in High-Risk Indian T2D Patients: The BRIDGE-DS study (168 T2D patients with heart failure; mean age 55.5 years) revealed compelling organ-protective effects after three months. HbA1c decreased by 1.5% (8.9% to 7.4%), NT-proBNP decreased by 122.7 pg/mL (306.7 to 184.0 pg/mL), and ejection fraction improved by 2.9 percentage points (43.1% to 46.0%)—all p<0.001. Blood pressure reduced dramatically (systolic -18 mmHg, diastolic -11.4 mmHg), while eGFR rose 10.9 mL/min/1.73m² (63.1 to 74.0 mL/min/1.73m²)—a 17% gain in renal function. The combination of dapagliflozin and sitagliptin proved safe and well-tolerated across the T2D with HF population. [8]

Initiation of Dapagliflozin & Sitagliptin FDC: Relevant Guideline Considerations

International and national guidelines advocate early combination therapy.

Key Takeaways:

• Young-onset T2D is a growing epidemic in India, with prevalence rising from as early as 25–34 years and nearly doubled incidence among 20–39-year-olds, demanding early intensive intervention.[1,2]
• Dapagliflozin and Sitagliptin act via complementary beta-cell independent pathways, synergistically improving glycemia, weight, and cardiorenal health.[6]
• Dapagliflozin–sitagliptin combination lowered HbA1c by 1.1%, and improved eGFR by 5.3 mL/min/1.73 m² & reduced BP within 3–4 months in Indian T2DM patients. [7]
• Dapagliflozin–sitagliptin combination also reduced NT-proBNP by 122.7 pg/mL, improved ejection fraction, BP normalized, and increased eGFR by 17%, confirming broad cardio-renal benefit. [8]

Abbreviations: ADA - American Diabetes Association, ASCVD - Atherosclerotic Cardiovascular Disease, BMI - Body Mass Index, BP - Blood Pressure, CKD - Chronic Kidney Disease, CV - Cardiovascular, CVD - Cardiovascular Disease, DKD - Diabetic Kidney Disease, DPP-4 - Dipeptidyl Peptidase-4, DPP4i - Dipeptidyl Peptidase-4 inhibitor, eGFR - estimated Glomerular Filtration Rate, FDC - Fixed Dose Combination, GIP - Glucose-Dependent Insulinotropic Polypeptide, GLP-1 - Glucagon-Like Peptide-1, HF - Heart Failure, MACE - Major Adverse Cardiovascular Events, NT-proBNP - N-Terminal pro-B-Type Natriuretic Peptide, RSSDI - Research Society for the Study of Diabetes in India, SBP - Systolic Blood Pressure, SGLT-2 - Sodium-Glucose Co-Transporter-2, SGLT2i - Sodium-Glucose Co-Transporter-2 inhibitor, T2DM - Type 2 Diabetes Mellitus, uACR - urine Albumin-to-Creatinine Ratio.