Type 2 diabetes (T2D) is a growing epidemic in India. India has 101 million people with diabetes and 136 million with prediabetes, with disease onset occurring at much younger ages than in other populations. Prevalence begins to rise as early as 25–34 years, and incidence among those aged 20–39 years has nearly doubled. [1] Alarmingly, over one-third of 20–29-year-olds have metabolic obesity despite normal BMI (<25 kg/m²), associated with significantly elevated risk for diabetes, cardiovascular and renal disease, yet evades conventional screening. [2] 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. When to Initiate Combination Key Recommendation ADA 2025 [9[ Early combination therapy is recommended to shorten the time to glycemic goals (Level A) SGLT2 inhibitor strongly recommended in patients with ASCVD, heart failure, or CKD (eGFR 20–60 mL/min/1.73 m² or albuminuria) to reduce cardiovascular events, hospitalization for heart failure, and slow CKD progression Combination therapy is advised when HbA1c is more than 1.5% above the target SGLT2 inhibitor preferred for ASCVD, HF, DKD, or weight reduction needs. DPP-4 inhibitor preferred when hypoglycemia risk is high Indian Expert Consensus 2025 [11] Supports early initiation of dapagliflozin–sitagliptin fixed-dose combination Recommended in established CVD, elevated HbA1c, or renal impairment. Demonstrated benefits in MACE reduction, weight loss, blood pressure control, heart failure risk reduction, and lipid profile improvement (Level A) Key Takeaways: 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.