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Efficacy and safety of dipeptidyl peptidase-4 inhibitors in type 2 diabetes mellitus patients with moderate to severe renal impairment: a systematic review and meta-analysis.

Cheng D, Fei Y, Liu Y, Li J, Chen Y, Wang X, Wang N - PLoS ONE (2014)

Bottom Line: Furthermore, DPP-4 inhibitors were well-tolerated, without any additional mortality and adverse events.However, the quality of evidence was mostly as low, as assessed using the GRADE system for each outcome.DPP-4 inhibitors also have a potential advantage in lowering the risk of adverse events.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.

ABSTRACT

Objective: To perform a systematic review and meta-analysis regarding the efficacy and safety of dipeptidyl peptidase-4 (DDP-4) inhibitors ("gliptins") for the treatment of type 2 diabetes mellitus (T2DM) patients with moderate to severe renal impairment.

Methods: All available randomized-controlled trials (RCTs) that assessed the efficacy and safety of DDP-4 inhibitors compared with placebo, no treatment, or active drugs were identified using PubMed, EMBASE, Cochrane CENTRAL, conference abstracts, clinical trials.gov, pharmaceutical company websites, the FDA, and the EMA (up to June 2014). Two independent reviewers extracted the data, and a random-effects model was applied to estimate summary effects.

Results: Thirteen reports of ten studies with a total of 1,915 participants were included in the final analysis. Compared with placebo or no treatment, DPP-4 inhibitors reduced HbA1c significantly (-0.52%, 95%CI -0.64 to -0.39) and had no increased risk of hypoglycemia (RR 1.10, 95%CI 0.92 to 1.32) or weight gain. In contrast to glipizide monotherapy, DPP-4 inhibitors showed no difference in HbA1c lowering effect (-0.08%, 95% CI -0.40 to 0.25) but had a lower incidence of hypoglycemia (RR 0.40, 95%CI 0.23 to 0.69). Furthermore, DPP-4 inhibitors were well-tolerated, without any additional mortality and adverse events. However, the quality of evidence was mostly as low, as assessed using the GRADE system for each outcome.

Conclusions: DPP-4 inhibitors are effective at lowering HbA1c in T2DM patients with moderate to severe renal impairment. DPP-4 inhibitors also have a potential advantage in lowering the risk of adverse events. Regarding the low quality of the evidence according to GRADE, additional well-designed randomized trials that focus on the safety and efficacy of DPP-4 inhibitors in various CKD stages are needed urgently.

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Related in: MedlinePlus

Study flow diagram for trial selection and exclusion.
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pone-0111543-g001: Study flow diagram for trial selection and exclusion.

Mentions: Figure 1 shows the flow diagram of trial selection. From the initial 607 records in the electronic databases, a total of 28 articles were examined in full, among which nine reports on seven studies (seven primary reports and two extensions) [16]–[24] were finally selected. Furthermore, four additional unpublished reports (three primary reports and one extension) [25]–[28] obtained from conference abstracts, ClinicalTrials.gov and company website were selected, yet one trial on gemigliptin conducted in October 2013 identified in ClinicalTrials.gov was excluded [29]. Ultimately, thirteen reports on ten RCT studies were included in this systematic review.


Efficacy and safety of dipeptidyl peptidase-4 inhibitors in type 2 diabetes mellitus patients with moderate to severe renal impairment: a systematic review and meta-analysis.

Cheng D, Fei Y, Liu Y, Li J, Chen Y, Wang X, Wang N - PLoS ONE (2014)

Study flow diagram for trial selection and exclusion.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4216116&req=5

pone-0111543-g001: Study flow diagram for trial selection and exclusion.
Mentions: Figure 1 shows the flow diagram of trial selection. From the initial 607 records in the electronic databases, a total of 28 articles were examined in full, among which nine reports on seven studies (seven primary reports and two extensions) [16]–[24] were finally selected. Furthermore, four additional unpublished reports (three primary reports and one extension) [25]–[28] obtained from conference abstracts, ClinicalTrials.gov and company website were selected, yet one trial on gemigliptin conducted in October 2013 identified in ClinicalTrials.gov was excluded [29]. Ultimately, thirteen reports on ten RCT studies were included in this systematic review.

Bottom Line: Furthermore, DPP-4 inhibitors were well-tolerated, without any additional mortality and adverse events.However, the quality of evidence was mostly as low, as assessed using the GRADE system for each outcome.DPP-4 inhibitors also have a potential advantage in lowering the risk of adverse events.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.

ABSTRACT

Objective: To perform a systematic review and meta-analysis regarding the efficacy and safety of dipeptidyl peptidase-4 (DDP-4) inhibitors ("gliptins") for the treatment of type 2 diabetes mellitus (T2DM) patients with moderate to severe renal impairment.

Methods: All available randomized-controlled trials (RCTs) that assessed the efficacy and safety of DDP-4 inhibitors compared with placebo, no treatment, or active drugs were identified using PubMed, EMBASE, Cochrane CENTRAL, conference abstracts, clinical trials.gov, pharmaceutical company websites, the FDA, and the EMA (up to June 2014). Two independent reviewers extracted the data, and a random-effects model was applied to estimate summary effects.

Results: Thirteen reports of ten studies with a total of 1,915 participants were included in the final analysis. Compared with placebo or no treatment, DPP-4 inhibitors reduced HbA1c significantly (-0.52%, 95%CI -0.64 to -0.39) and had no increased risk of hypoglycemia (RR 1.10, 95%CI 0.92 to 1.32) or weight gain. In contrast to glipizide monotherapy, DPP-4 inhibitors showed no difference in HbA1c lowering effect (-0.08%, 95% CI -0.40 to 0.25) but had a lower incidence of hypoglycemia (RR 0.40, 95%CI 0.23 to 0.69). Furthermore, DPP-4 inhibitors were well-tolerated, without any additional mortality and adverse events. However, the quality of evidence was mostly as low, as assessed using the GRADE system for each outcome.

Conclusions: DPP-4 inhibitors are effective at lowering HbA1c in T2DM patients with moderate to severe renal impairment. DPP-4 inhibitors also have a potential advantage in lowering the risk of adverse events. Regarding the low quality of the evidence according to GRADE, additional well-designed randomized trials that focus on the safety and efficacy of DPP-4 inhibitors in various CKD stages are needed urgently.

Show MeSH
Related in: MedlinePlus