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Evidence summaries

Incretin-Based Therapy with Dipeptidyl Peptidase 4 Inhibitors in Type 2 Diabetes

Dipeptidyl peptidase 4 inhibitors in adults with type 2 diabetes are moderately effective in improving glycaemic control compared with placebo, but are clearly inferior to SGLT-2 inhibitors or GLP-1 agonists. Moreover, they do not reduce all-cause mortality. Level of evidence: "A"

A network meta-analysis 3 including 236 RCTs with a total of 176 310 participants assessed the efficacies of SGLT-2 inhibitors (SGLT-2i) , GLP-1 agonists (GLP-1a), and DPP-4 inhibitors (DPP-4i) on mortality and cardiovascular end points. SGLT-2i and GLP-1a were associated with significantly lower all-cause mortality than the control groups (placebo or no treatment). DPP-4i were not significantly associated with lower all-cause mortality (aRD 0.1%; HR, 1.02; 95% CrI 0.94 to 1.11) compared to control groups.

A Cochrane review [Abstract] 2 included 44 studies with a total of 13 036 subjects. DPP-4 inhibitors reduced HbA1c (table T1) compared with placebo but had little or no effect on fasting blood glucose and cardiovascular death.

DPP-4 inhibitors versus placebo for people with diabetes and CKD

OutcomeEffect estimate (95% CI)Control - Risk with placeboRisk with intervention - DPP-4 inhibitorsNo. of participants (studies)
Mean difference in HbA1c %and [HbA1c mmol/mol]-- 0.62% lower (0.39 to 0.62 lower) and [6.8 mmol/mol lower (4.3 to 9.3 lower)]867 (7)
Death (all causes)RR 0.89 (0.75 to 1.07)108 per 100096 per 1000 (81 to 115)4211 (6)
All cardiovascular deathRR 0.93(0.77 to 1.11)77 per 100071 per 1000 (59 to 85)5897 (2)
Weight (kg)MD 0.16(-0.58 to 0.9) 0.16 kg higher (0.58 lower to 0.9 higher)210 (2)

References

  • Lo C, Toyama T, Wang Y et al. Insulin and glucose-lowering agents for treating people with diabetes and chronic kidney disease. Cochrane Database Syst Rev 2018;(9):CD011798. [PubMed]
  • Zheng SL, Roddick AJ, Aghar-Jaffar R et al. Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis. JAMA 2018;319(15):1580-1591. [PubMed]

Primary/Secondary Keywords