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Emerging role of dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes.

Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch C - Vasc Health Risk Manag (2008)

Bottom Line: However, every new compound for T2DM has to prove long-term safety especially on cardiovascular outcomes.Systematic review and meta-analysis of the effects of sitagliptin and vildagliptin therapy on main efficacy parameters and safety.Long-term data on cardiovascular outcomes and safety are needed before widespread use of these new agents.

View Article: PubMed Central - PubMed

Affiliation: Cochrane Metabolic and Endocrine Disorders Group, Department of General Practice, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany. richterb@uni-duesseldorf.de

ABSTRACT

Background: In type 2 diabetes mellitus (T2DM) there is a progressive loss of beta-cell function. One new approach yielding promising results is the use of the orally active dipeptidyl peptidase-4 (DPP-4) inhibitors. However, every new compound for T2DM has to prove long-term safety especially on cardiovascular outcomes.

Objectives: Systematic review and meta-analysis of the effects of sitagliptin and vildagliptin therapy on main efficacy parameters and safety. SELECTION CRITERIA, DATA COLLECTION, AND ANALYSIS: Randomized controlled clinical studies of at least 12 weeks' duration in T2DM.

Results: DPP-4 inhibitors versus placebo showed glycosylated hemoglobin A1c (A1c) improvements of 0.7% versus placebo but not compared to monotherapy with other hypoglycemic agents (0.3% in favor of controls). The overall risk profile of DPP-4 inhibitors was low, however a 34% relative risk increase (95% confidence interval 10% to 64%, P = 0.004) was noted for all-cause infection associated with sitagliptin use. No data on immune function, health-related quality of life and diabetic complications could be extracted.

Conclusions: DPP-4 inhibitors have some theoretical advantages over existing therapies with oral antidiabetic compounds but should currently be restricted to individual patients. Long-term data on cardiovascular outcomes and safety are needed before widespread use of these new agents.

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Related in: MedlinePlus

Mean HbA1c changes [%] from baseline to (imputed) endpoint in sitagliptin randomised controlled trials. Weighted mean differences by means of random-effects model (inverse varicance (IV) method) showing 95% confidence intervals (CI) for single studies and pooled effect sizes. I2 describes the percentage of total variation across studies due to heterogeneity.Abbreviations: HbA1c, hemoglobin A1c.
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f4-vhrm-4-0753: Mean HbA1c changes [%] from baseline to (imputed) endpoint in sitagliptin randomised controlled trials. Weighted mean differences by means of random-effects model (inverse varicance (IV) method) showing 95% confidence intervals (CI) for single studies and pooled effect sizes. I2 describes the percentage of total variation across studies due to heterogeneity.Abbreviations: HbA1c, hemoglobin A1c.

Mentions: Figure 2.1.1 reveals the effects of sitagliptin treatment on A1c mean changes. The first panel provides an overview of all study arms for illustrating purposes only. Compared with placebo, sitagliptin resulted in a significant reduction of A1c (−0.7%, 95% CI −0.9% to −0.6%, P < 0.00001). Contrasted to another single hypoglycemic agent, sitagliptin was inferior (mean difference 0.3%, 95% CI 0.1 to 0.6, P = 0.007). Sitagliptin combination therapy lead to additional lowering of A1c but heterogeneity was substantial. The effects of sitagliptin on metabolic control did also not diminish if the A1c of 12 weeks’ versus 24 weeks’ treatment and against placebo were compared.


Emerging role of dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes.

Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch C - Vasc Health Risk Manag (2008)

Mean HbA1c changes [%] from baseline to (imputed) endpoint in sitagliptin randomised controlled trials. Weighted mean differences by means of random-effects model (inverse varicance (IV) method) showing 95% confidence intervals (CI) for single studies and pooled effect sizes. I2 describes the percentage of total variation across studies due to heterogeneity.Abbreviations: HbA1c, hemoglobin A1c.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2597770&req=5

f4-vhrm-4-0753: Mean HbA1c changes [%] from baseline to (imputed) endpoint in sitagliptin randomised controlled trials. Weighted mean differences by means of random-effects model (inverse varicance (IV) method) showing 95% confidence intervals (CI) for single studies and pooled effect sizes. I2 describes the percentage of total variation across studies due to heterogeneity.Abbreviations: HbA1c, hemoglobin A1c.
Mentions: Figure 2.1.1 reveals the effects of sitagliptin treatment on A1c mean changes. The first panel provides an overview of all study arms for illustrating purposes only. Compared with placebo, sitagliptin resulted in a significant reduction of A1c (−0.7%, 95% CI −0.9% to −0.6%, P < 0.00001). Contrasted to another single hypoglycemic agent, sitagliptin was inferior (mean difference 0.3%, 95% CI 0.1 to 0.6, P = 0.007). Sitagliptin combination therapy lead to additional lowering of A1c but heterogeneity was substantial. The effects of sitagliptin on metabolic control did also not diminish if the A1c of 12 weeks’ versus 24 weeks’ treatment and against placebo were compared.

Bottom Line: However, every new compound for T2DM has to prove long-term safety especially on cardiovascular outcomes.Systematic review and meta-analysis of the effects of sitagliptin and vildagliptin therapy on main efficacy parameters and safety.Long-term data on cardiovascular outcomes and safety are needed before widespread use of these new agents.

View Article: PubMed Central - PubMed

Affiliation: Cochrane Metabolic and Endocrine Disorders Group, Department of General Practice, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany. richterb@uni-duesseldorf.de

ABSTRACT

Background: In type 2 diabetes mellitus (T2DM) there is a progressive loss of beta-cell function. One new approach yielding promising results is the use of the orally active dipeptidyl peptidase-4 (DPP-4) inhibitors. However, every new compound for T2DM has to prove long-term safety especially on cardiovascular outcomes.

Objectives: Systematic review and meta-analysis of the effects of sitagliptin and vildagliptin therapy on main efficacy parameters and safety. SELECTION CRITERIA, DATA COLLECTION, AND ANALYSIS: Randomized controlled clinical studies of at least 12 weeks' duration in T2DM.

Results: DPP-4 inhibitors versus placebo showed glycosylated hemoglobin A1c (A1c) improvements of 0.7% versus placebo but not compared to monotherapy with other hypoglycemic agents (0.3% in favor of controls). The overall risk profile of DPP-4 inhibitors was low, however a 34% relative risk increase (95% confidence interval 10% to 64%, P = 0.004) was noted for all-cause infection associated with sitagliptin use. No data on immune function, health-related quality of life and diabetic complications could be extracted.

Conclusions: DPP-4 inhibitors have some theoretical advantages over existing therapies with oral antidiabetic compounds but should currently be restricted to individual patients. Long-term data on cardiovascular outcomes and safety are needed before widespread use of these new agents.

Show MeSH
Related in: MedlinePlus