COMPARATIVE EFFECTIVENESS OF SECOND-LINE ORAL ANTIDIABETIC TREATMENTS ADDED TO METFORMIN MONOTHERAPY IN PEOPLE WITH TYPE 2 DIABETES
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Keywords
Type 2 diabetes mellitus; metformin; second-line therapy; sulfonylurea; DPP-4 inhibitors; thiazolidinediones; glycemic control.
Abstract
Background: When metformin monotherapy fails to achieve glycemic control in type 2 diabetes mellitus (T2DM), selection of optimal second-line oral antidiabetic therapy remains challenging. Evidence comparing the real-world effectiveness of different second-line agents added to metformin is limited. This study aimed to compare the glycemic efficacy, weight effects, and safety profiles of sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, and thiazolidinediones as second-line treatments added to metformin in patients with T2DM.
Methods: This retrospective cohort study analyzed 847 patients with T2DM who initiated second-line oral therapy after metformin monotherapy failure between January 2011 and December 2012. Patients were categorized into three groups: sulfonylurea (n=312), DPP-4 inhibitor (n=298), and thiazolidinedione (n=237). Primary outcomes included change in glycated hemoglobin (HbA1c) at 12 months. Secondary outcomes comprised body weight change, hypoglycemic events, and treatment persistence.
Results: Mean baseline HbA1c was comparable across groups (8.4 ± 1.1%). At 12 months, all groups demonstrated significant HbA1c reductions. Sulfonylureas achieved the greatest reduction (-1.24 ± 0.82%; p<0.001), followed by DPP-4 inhibitors (-0.89 ± 0.71%; p<0.001) and thiazolidinediones (-0.94 ± 0.78%; p<0.001). However, sulfonylureas were associated with significant weight gain (+2.1 ± 1.8 kg; p<0.001) and higher hypoglycemia rates (18.6% vs. 3.4% for DPP-4 inhibitors; p<0.001). DPP-4 inhibitors demonstrated weight neutrality (+0.3 ± 1.2 kg; p=0.284) and superior treatment persistence (82.5% vs. 71.8% for sulfonylureas; p=0.002).
Conclusion: While sulfonylureas provide superior short-term glycemic efficacy as second-line therapy, DPP-4 inhibitors offer comparable effectiveness with favorable weight and safety profiles. Treatment selection should incorporate individual patient characteristics, hypoglycemia risk, and weight management goals.
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Dr. Amar Jeeth Raja R
Department of Pharmacology Assistant Professor Sri Lakshmi Narayana Institute of Medical Sciences, Osudu, Agaram Village, Villianur Commune, Kudapakkam Post, Puducherry- 605502
