Cardiac Autonomic Outcomes Following Canagliflozin Add-On Therapy in Type 2 Diabetes Patients with Inadequate Glycemic Control: A Prospective and Observational Study

Introduction: Cardiac autonomic neuropathy (CAN), a serious complication of type 2 diabetes mellitus (T2DM), contributes to adverse cardiovascular outcomes through autonomic imbalance. Emerging evidence suggests that sodium-glucose cotransporter 2 inhibitors may modulate autonomic tone in addition to their established metabolic benefits. Methods: A 24-month, prospective, and observational study was conducted among adults aged 18–75 years with T2DM for ≥5 years and inadequate glycemic control (glycosylated hemoglobin – HbA1c >7% but <9%) despite oral therapy. Participants ( n = 120) were initiated on canagliflozin and followed for 12 months. Cardiac autonomic function was assessed at baseline, 6, and 12 months using the Ewing’s criteria, including the E: I ratio, 30:15 ratio, Valsalva ratio, postural BP change, handgrip BP response, and heart rate variability. Secondary outcomes included changes in glycemic indices, renal function, body weight, adherence, and adverse effects. Results: Significant improvements were observed in fasting/postprandial glucose, HbA1c, serum creatinine, and urine albumin creatinine ratio. low-frequency to high-frequency ratio decreased significantly at 12 months ( P = 0.03), suggesting improved sympathovagal balance. E: I ratio showed mild but significant decline, while other autonomic parameters remained stable. At 12 months, 96.7% of participants had normal CAN scores. No significant associations were found between CAN status and age, duration of diabetes, or HbA1c. Conclusion: Canagliflozin may modestly improve autonomic function while significantly enhancing glycemic and renal parameters. Larger randomized trials are warranted to confirm autonomic benefits in high-risk T2DM populations.