SGLT-2 Inhibitors and DPP-4 Inhibitors as Second-Line Drugs in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Clinical Trials

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.

Comparative effectiveness of dapagliflozin vs DPP‐4 inhibitors on a composite endpoint of HbA1c, body weight and blood pressure reduction in the real world

“…In phase III randomized controlled trials (RCTs), add‐on therapy with SGLT2i yielded similar or greater improvement of HbA1c than DPP‐4i, 13, 14 and greater improvements in body weight and systolic blood pressure (SBP) 14, 15 . However, only a few studies evaluated the simultaneous attainment of multiple risk factor goals.…”

Sodium‐glucose co‐transporter‐2 inhibitors and the risk of urosepsis: A multi‐site, prevalent new‐user cohort study

“…Meta-analyses comparing SGLT2i to active treatments usually found no difference in UTI. 10,29,30 On the other hand, compared with placebo or a combination of placebo and active treatment, SGLT2i treatment had an increased UTI risk. [7][8][9][31][32][33] In three meta-analyses, SGLT2i had similar risk for UTI compared with DPP4i.…”

“…[7][8][9][31][32][33] In three meta-analyses, SGLT2i had similar risk for UTI compared with DPP4i. 30,31,34 Inconsistencies in the results of the metaanalyses could also be related to the specific SGLT2i molecule studied; early metaanalyses, which included mainly studies on dapagliflozin, often found an increase in UTI. [35][36][37][38] Similarly, more recent large meta-analyses found that dapagliflozin was associated with an increased risk of UTI, while canagliflozin and empagliflozin were not.…”

Effects of incretin-based therapies on β-cell function in type 1 diabetes mellitus: a systematic review and meta-analysis

“…GLP-1 RAs and DPP-4Is have salient effects on glucose management, resulting in improved b-cell function in patients with T2DM. [5][6][7] Based on their potential beneficial effects and promising results in animal studies, incretin-based drugs have been clinically tested in patients with T1DM or SPIDDM/LADA; [8][9][10][11] however, their beneficial effects on b-cell function in individuals with T1DM remain unclear. Ahr en et al 12 found no significant difference in mean plasma C-peptide levels between patients with T1DM with detectable C-peptides treated with any liraglutide dose and placebo at 26 weeks.…”

“…GLP-1 RAs and DPP-4Is have salient effects on glucose management, resulting in improved β-cell function in patients with T2DM. 5 – 7 …”