Improved Glycemic Control Without Weight Gain Using Triple Therapy in Type 2 Diabetes

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To evaluate the safety and effectiveness of triple therapy using insulin, metformin, and a thiazolidinedione following a course of dual therapy using insulin and metformin or insulin and a thiazolidinedione in type 2 diabetes.


Twenty-eight type 2 diabetic subjects using insulin monotherapy (baseline HbA1c level 8.5%) who had been randomly assigned to insulin (INS) and metformin (MET) (INS + MET, n = 14) or INS and the thiazolidinedione troglitazone (TGZ) (INS + TGZ, n = 14) (dual therapy) for 4 months were given INS, MET, and TGZ (triple therapy: INS + MET, add TGZ; or INS + TGZ, add MET) for another 4 months. The INS dose was not increased.


HbA1c levels decreased in both groups during dual therapy and improved further during triple therapy (INS + MET 7.0 ± 0.8, INS + TGZ 6.2 ± 0.8, P < 0.0001; INS + MET, add TGZ 6.1 ± 0.4%, P < 0.001; INS + TGZ, add MET 5.8 ± 0.6%, P < 0.05; and INS + TGZ vs. INS + MET, P = 0.02). Significant reductions in total daily insulin dose occurred in the INS + TGZ (−14.1 units, P < 0.0001), INS + TGZ add MET (−13.7 units, P < 0.01), and the INS + MET add TGZ groups (−17.3 units, P < 0.003), but not in the INS + MET group (−3.2 units) (INS + TGZ vs. INS + MET P < 0.05). Subjects in the INS + TGZ group experienced significant weight gain (4.4 ± 2.7 kg, P < 0.0005). No weight gain occurred in the INS + MET, INS + MET add TGZ, and INS + TGZ add MET groups.


Triple therapy using INS, MET, and TGZ resulted in lower HbA1c levels and total daily insulin dose than during dual therapy. The use of triple therapy resulted in 100% of subjects achieving an HbA1c <7.0%, while decreasing the dose of INS. Weight gain was avoided when MET therapy preceded the addition of TGZ therapy. The addition of TGZ resulted in the greatest reductions in HbA1c levels and insulin dose. Triple therapy using INS, MET, and a thiazolidinedione (such as TGZ) can be a safe and effective treatment in type 2 diabetes.

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