1.
Double-blind, randomized clinical trial comparing the efficacy and safety of continuing or discontinuing the dipeptidyl peptidase-4 inhibitor sitagliptin when initiating insulin glargine therapy in patients with type 2 diabetes: The CompoSIT-I Study.
Roussel, R, Duran-García, S, Zhang, Y, Shah, S, Darmiento, C, Shankar, RR, Golm, GT, Lam, RLH, O'Neill, EA, Gantz, I, et al
Diabetes, obesity & metabolism. 2019;(4):781-790
-
-
Free full text
-
Abstract
AIMS: To compare the effects of continuing versus discontinuing sitagliptin when initiating and intensively titrating insulin glargine. MATERIALS AND METHODS Eligible patients had inadequately controlled type 2 diabetes on metformin (≥1500 mg/d) in combination with a dipeptidyl peptidase-4 (DPP-4) inhibitor and/or a sulphonylurea. Those on metformin + sitagliptin were directly randomized; all others were switched to metformin + sitagliptin (discontinuing other DPP-4 inhibitors and sulphonylureas) and stabilized during a run-in period. At randomization, patients were allocated to continuing sitagliptin or discontinuing sitagliptin, with both groups initiating insulin glargine and titrating to a target fasting glucose of 4.0 to 5.6 mmol/L. RESULTS A total of 743 participants (mean glycated haemoglobin [HbA1c] 72.6 mmol/mol [8.8%], disease duration 10.8 years), were treated. After 30 weeks, the mean HbA1c and least squares (LS) mean change from baseline in HbA1c were 51.4 mmol/mol (6.85%) and -20.5 mmol/mol (-1.88%) in the sitagliptin group and 56.4 mmol/mol (7.31%) and -15.5 mmol/mol (-1.42%) in the placebo group; the difference in LS mean changes from baseline HbA1c was -5.0 mmol/mol (-0.46%; P < 0.001). The percentage of participants with HbA1c <53 mmol/mol (<7.0%) was higher (54% vs. 35%) and the mean daily insulin dose was lower (53 vs. 61 units) in the sitagliptin group. Despite lower HbA1c, event rates and incidences of hypoglycaemia were not higher in the sitagliptin group. Adverse events overall and changes from baseline in body weight were similar between the two treatment groups. CONCLUSION When initiating insulin glargine therapy, continuation of sitagliptin, compared with discontinuation, resulted in a clinically meaningful greater reduction in HbA1c without an increase in hypoglycaemia. ClinicalTrials.gov Identifier: NCT02738879.
2.
SGLT-2 Inhibitors and DPP-4 Inhibitors as Second-Line Drugs in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Clinical Trials.
Wang, K, Zhang, Y, Zhao, C, Jiang, M
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2018;(10):768-777
Abstract
Sodium-glucose co-transporter 2 (SGLT-2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors are both novel and second-line therapies in type 2 diabetes mellitus, yet no well-rounded comparison of these two drugs has been published. Upon searching randomized controlled trials in databases from inception to July 2018, we collected studies on the efficacy or safety of SGLT-2 inhibitors compared with those of DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. A total of 12 randomized controlled studies including 4342 patients were included in this meta-analysis. Compared with DPP-4 inhibitors, SGLT-2 inhibitors achieved greater reductions in HbA1c (SMD -0.22; 95% CI: -0.30, -0.14; p=0.000) and fasting plasma glucose (SMD -0.48; 95% CI: -0.56, -0.41; p=0.000). In addition, these reductions increased with a prolonged treatment duration from 12 to 78 weeks. Geographically, significant reductions of SGLT-2 inhibitors in HbA1c and FPG were found in North America and Europe, but not in Asia. Furthermore, SGLT-2 inhibitors showed greater reductions in body weight (SMD -0.72; 95% CI: -0.81, -0.63; p=0.000) from baseline, with an increased incidence of genital infections (OR 4.49; 95% CI: 2.96, 6.83; p=0.000) and pollakiuria (OR 2.24; 95% CI: 1.05, 4.79; p=0.037) and a decreased incidence of hypertension and hyperglycemia. Overall, the current meta-analysis demonstrated that compared to DPP-4 inhibitors, SGLT-2 inhibitors have beneficial effects on HbA1c, FPG, body weight, SBP, DBP, and HDL-cholesterol in patients with type 2 diabetes. However, SGLT-2 inhibitors are associated with increased total cholesterol and LDL-cholesterol and a higher incidence of genital infections and pollakiuria.