Sitagliptin Compared with Thiazolidinediones as a Third-Line Oral Antihyperglycemic Agent in Type 2 Diabetes Mellitus

Abstract

Objective To compare sitagliptin and thiazolidinediones as third-line oral antihyperglycemic agents among ethnic minority patients with poorly controlled type 2 diabetes mellitus. Methods In an open-label, single-arm design, we treated type 2 diabetic patients who had suboptimal diabetes control on maximum tolerated dosages of metformin plus sulfonylureas with the addition of sitagliptin, 100 mg daily, and compared their responses with findings from a historical control group of similar patients treated with rosiglitazone, 8 mg daily, or pioglitazone, 45 mg daily, as their third-line oral agent. Patients were assessed bimonthly, and those who achieved hemoglobin A1c levels less than 7.5% at 4 months continued through 1 year of follow-up. Results One hundred eight patients were treated with sitagliptin, and 104 patients constituted the historical control group treated with rosiglitazone or pioglitazone. At baseline, sitagliptin- and thiazolidinedione-treated patients had identical hemoglobin A1c levels (mean ± SD) (9.4 ± 1.8% and 9.4 ± 1.9%, respectively) and similar known diabetes duration (6.7 ± 5.0 years and 7.6 ± 5.8 years, respectively). Hemoglobin A1c was reduced in both groups at 4 months (P<.001), but the reduction was greater with thiazolidinediones than with sitagliptin (−2.0 ± 1.7% vs −1.3 ± 1.8%; P = .006), as was the proportion of patients achieving a hemoglobin A1c level less than 7.5% (62% vs 46%; P = .026). Of all patients achieving a hemoglobin A1c level less than 7.5% at 4 months, the same proportions in each group sustained their hemoglobin A1c level less than 7.5% by 12 months (59% vs 58%). Sitagliptin was well tolerated. Conclusions Among ethnic minority patients with poorly controlled type 2 diabetes while taking maximum tolerated dosages of metformin and sulfonylureas, third-line add-on therapy with a thiazolidinedione controlled hyperglycemia more effectively than sitagliptin after 4 months.

DPP-4 inhibitors in the management of type 2 diabetes: A critical review of head-to-head trials

“…One study compared two modalities of triple therapy. Among ethnic-minority T2DM patients poorly controlled with the maximum tolerated doses of metformin and SU, third-line add-on therapy with TZD (rosiglitazone 8mg or pioglitazone 45 mg) was found to control hyperglycaemia more effectively than sitagliptin 100 mg after 4 months [63]. …”

“…Again, most studies, except one [63], were randomized clinical trials comparing the addition of a gliptin vs a placebo on top of a dual combination of either metformin-SU [45,64] or metformin-TZD [65]. Sitagliptin 100mg once daily significantly improved glycaemic control and β-cell function in patients with T2DM who had inadequate glycaemic control with glimepiride plus metformin therapy [45].…”

Comparison of efficacy of add-on therapy of vildagliptin versus pioglitazone among Type 2 Diabetes Mellitus patients inadequately controlled on dual therapy of metformin plus sulfonylurea

“…The third-line add-on therapy with a thiazolidinedione, controlled hyperglycemia more effectively than sitagliptin after four months of use. 12 Rosenstock J et al, 2006 evaluated the efficacy and safety of insulin glargine and rosiglitazone among patients on metformin and sulfonylurea. The HbA 1c improvements were similar in both the groups, but when baseline was more than 9.5%, insulin glargine led to a greater improvement as compared to rosiglitazone (p < 0.05).…”

Comparison Between Pioglitazone/Metformin Combination Therapy and Sitagliptin/Metformin Combination Therapy on the Efficacy in Chinese Type 2 Diabetic Adults Insufficiently Controlled with Metformin: Study Protocol of an Open-Label, Multicenter, Non-Inferiority Parallel-Group Randomized Controlled Trial

“…Some studies have compared the effects of pioglitazone and sitagliptin, most of which investigated the differences in their hypoglycemic effects and safety profiles. Findings regarding the comparative effects of the drugs on HbA1c reduction are mixed, with some studies reporting that pioglitazone was superior to sitagliptin, [21][22][23] and others not supporting this finding. [24][25][26] Reasons for these inconsistent findings may include different pioglitazone dosages, different drug combinations, and varying treatment durations.…”

“…Specifically, these studies reported that pioglitazone was inferior to sitagliptin in terms of weight control, and both drugs were generally well tolerated. [21][22][23][24][25][26] noting that none of the studies based their conclusion on patients with T2D from mainland China. A propensity score-matched analysis found that compared with DPP4 inhibitors, TZD was significantly better at alleviating IR and inferior at improving β cell function.…”