Real-World Evidence of Tirzepatide in Indian Adults With Type 2 Diabetes: Significant Early Glycemic and Cardiometabolic Benefits

Background: Tirzepatide, a novel dual GIP/GLP-1 receptor agonist, has demonstrated superior glycemic efficacy in randomized clinical trials. However, real-world data in Indian populations remain limited. Objective: The primary objective of this multicenter retrospective study was to evaluate the change in glycated hemoglobin (HbA1c) at 12 weeks (three months) following initiation of tirzepatide in Indian adults with type 2 diabetes mellitus treated in routine clinical practice. Secondary objectives included assessment of changes in body weight, blood pressure, lipid parameters, hepatic fibrosis index (FIB-4), and evaluation of tolerability and treatment persistence during follow-up. Methods: This retrospective multicenter study included 71 adults with type 2 diabetes who completed three months of tirzepatide therapy across seven centers in Lucknow, Uttar Pradesh. The primary outcome was the change in HbA1c. Secondary outcomes included body weight, blood pressure, lipid parameters, liver enzymes, FIB-4 index, and evaluation of tolerability and treatment persistence. Results: Mean HbA1c decreased significantly from 8.7 ± 1.4% to 6.9 ± 1.0% (mean change −1.8 ± 1.2%, p<0.001), with 59.2% achieving HbA1c <7% at three months. Mean body weight declined by 4.7 ± 3.2 kg (5.7%, p<0.001). Significant improvements were observed in systolic blood pressure (−5.6 mmHg), total cholesterol (−16.6 mg/dL), LDL-cholesterol (−12.2 mg/dL), HDL-cholesterol (+2.6 mg/dL), triglycerides (−46.4 mg/dL), and liver enzymes (all p<0.001). FIB-4 index decreased from 1.24 ± 0.68 to 1.08 ± 0.54 (p=0.004). Gastrointestinal adverse events occurred in 59.2% of patients, predominantly mild to moderate. The treatment discontinuation rate was 22.2%, mainly due to gastrointestinal intolerance (36%) and financial constraints (32%). Conclusion: In routine clinical practice, tirzepatide was associated with substantial glycemic improvement and meaningful weight loss at 12 weeks, along with favorable changes in cardiometabolic risk factors (blood pressure, lipids, hepatic indices). While the safety profile was consistent with global clinical trial data, real-world treatment persistence was significantly influenced by tolerability and affordability, highlighting important context-specific barriers in the Indian healthcare setting. Cost remains a key barrier to long-term use.