Role Of Dipeptidyl Peptidase-4 Inhibitors Research Articles

PRE1BRAZIL Protocol: A Randomized Controlled Trial to Evaluate the Effectiveness and Safety of the DPP-4 Inhibitor Alogliptin in Delaying the Progression of Stage 2 Type 1 Diabetes.

The incidence of Type 1 Diabetes Mellitus (T1DM) is on the rise. Since there is no curative treatment, it is urgent to look for therapies that can delay disease progression and protect pancreatic β-cells. Dipeptidyl peptidase-4 inhibitors (DPP-4i) have shown potential in modulating inflammation and preventing β-cell destruction. This protocol describes an upcoming trial to evaluate the effectiveness of the DPP-4i alogliptin in delaying the progression of stage 2 (presymptomatic) to stage 3 (symptomatic) T1DM. We propose a two-year, two-arm, multicenter, randomized, open-label clinical trial targeting Brazilian patients aged 18 to 35 with stage 2 T1DM. The study, facilitated by the custom-developed "PRE1BRAZIL" web application, aims to enroll 130 participants. They will be randomly assigned in a 1:1 ratio to either a treatment group (alogliptin 25 mg daily plus regular clinical and laboratory assessments) or a control group (regular assessments only). The primary outcome is the rate of progression to stage 3 T1DM. Secondary outcomes include changes in A1c levels, glucose levels during a 2-hour oral glucose tolerance test (OGTT), C-peptide levels, exogenous insulin requirements, Insulin-Dose Adjusted A1c (IDAA1c), and the incidence of diabetic ketoacidosis (DKA) in those advancing to stage 3. This protocol outlines the first randomized clinical trial (RCT) to investigate the impact of a DPP-4i in the presymptomatic stage of T1DM. The trial is designed to provide critical insights into the role of DPP-4i in the secondary prevention of T1DM. Utilizing the "PRE1BRAZIL" web application is expected to enhance participant enrollment and reduce operational costs. Brazilian Registry of Clinical Trials.

Risk of Pancreatic Cancer and Use of Dipeptidyl Peptidase 4 Inhibitors in Patients with Type 2 Diabetes: A Propensity Score-Matching Analysis.

The effects of dipeptidyl peptidase 4 (DPP-4) inhibitors over the course of long-term treatment remain unclear, and concerns have been raised regarding the role of DPP-4 inhibitors in carcinogenesis in the pancreas. Earlier studies of pancreatic adverse events have reported conflicting results. This study analyzed Korean National Health Insurance Service data from January 2009 to December 2012. Patients who had type 2 diabetes mellitus and took two or more oral glucose-lowering drugs (GLDs) were included. Patients prescribed DPP-4 inhibitors (n=51,482) or other GLDs (n=51,482) were matched at a 1:1 ratio using propensity score matching. The risk of pancreatic cancer was calculated using Kaplan-Meier curves and Cox proportional-hazards regression analysis. During a median follow-up period of 7.95 years, 1,051 new cases of pancreatic cancer were identified. The adjusted hazard ratio (HR) for DPP-4 inhibitor use was 0.99 (95% confidence interval [CI], 0.88 to 1.12) compared with the other GLD group. In an analysis limited to cases diagnosed with pancreatic cancer during hospitalization, the adjusted HR for the use of DPP-4 inhibitors was 1.00 (95% CI, 0.86 to 1.17) compared with patients who took other GLDs. Using the other GLD group as the reference group, no trend was observed for elevated pancreatic cancer risk with increased DPP-4 inhibitor exposure. In this population-based cohort study, DPP-4 inhibitor use over the course of relatively long-term follow-up showed no significant association with an elevated risk of pancreatic cancer.

Understanding the Role of Dipeptidyl Peptidase-4 Inhibitors in COVID-19: Findings From a Systematic Review

Background: Inhibitors of dipeptidyl peptidase-4 (DPP4) have been used for diabetic patients and there is debate around using the same DPP4 inhibitors as a potential source of treatment for severe coronavirus disease 2019 (COVID-19). The findings from individual studies regarding the usage of DDP4 inhibitors on COVID infection are available but not reviewed and synthesized. Therefore, we aimed to conduct a systematic review to synthesize the findings regarding its effect on the COVID infection course and the outcome. Methods: We carried out an electronic search in Google Scholar and PubMed. We considered a study eligible if it was an original research study, published in English during the era of COVID-19 till September 2021, and had provided information on the topic of DPP4 inhibitors and COVID infection followed by reviewing the full-text articles and summarizing their findings. Results: This review provided novel insights into the effect of DDP4 inhibitor users and its effect on COVID-19 patients. Overall, literature is scarce on the effect of DDP4 inhibitors on COVID severity and we found mixed results regarding the DDP4 effects on disease severity and mortality. The evidence is not consistent currently as some of the studies supported the role of DDP4 inhibitor, while other studies provided contradictory findings. UK population data published in 2021 with 2.5 million diabetic patients found no evidence to support a protective effect of DDP inhibitors on morbidity and mortality related to COVID-19. Conclusion: The findings of the review reveal that there is some benefit of the usage of DDP4 inhibitors on COVID-19 morbidity and mortality. However, we highly recommend replicating the studies in different contexts before making any strong recommendations. Furthermore, the results need to be interpreted cautiously due to the scarcity of literature on the role of DDP4 inhibitors among diabetic patients with COVID-19. J Endocrinol Metab. 2022;12(1):10-18 doi: https://doi.org/10.14740/jem767

Therapeutic Role of Dipeptidyl Peptidase-4 Inhibitors in COVID-19

Background: Limited retrospective data suggest that dipeptidyl peptidase-4 (DPP-4) inhibitors such as sitagliptin may decrease mortality in patients with type 2 diabetes hospitalized with coronavirus disease 2019 (COVID-19). Objective: To review the strength of evidence that supports possible therapeutic role of DPP-4 inhibitors in COVID-19. Methods: PUBMED search until October 10, 2020. Search terms included COVID-19, DPP-4 inhibitors, sitagliptin, CD26, mortality, diabetes. Retrospective studies, pertinent animal investigations and pre-print studies are reviewed. Results: Three retrospective studies have shown that use of DPP-4 inhibitors was associated with significant mortality reduction of approximately 56- 87% in patients with diabetes admitted with COVID-19. In addition, in one of these studies, the use of sitagliptin before hospitalization was associated with greater number of hospital discharges, improvement of clinical status, reduced risk of transfer to intensive care unit (ICU) and need for mechanical ventilation compared with patients who were not receiving sitagliptin. Moreover, there was significant decrease in some pro-inflammatory markers in the sitagliptin group. A small retrospective study of 9 patients who were taking a DPP-4 inhibitor prior to admission did not find any significant effect of DPP-4 inhibitors on mortality and clinical outcomes after hospitalization. Results of another small study suggested increase susceptibility to COVID-19, but not to its severity, in patients taking DPP-4 inhibitors. Conclusions: Weak evidence derived from observational studies suggests possible beneficial effects of DPP-4 inhibitors use in patients with type 2 diabetes and COVID-19. Randomized trials are urgently needed to clarify the efficacy and safety of DPP-4 inhibitors in patients with COVID-19 with and without type 2 diabetes

Role of dipeptidyl peptidase-4 inhibitors in patients with diabetes infected with coronavirus-19.

The pandemic infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is widely increasing the patients affiliated with coronavirus disease 2019 (COVID-19) from last December of 2019. It is reported that the entry receptor of SARS-CoV-2 has been confirmed to be angiotensin-converting enzyme 2 (ACE2). Notably, whether the ACE-related inhibitors or drugs modulated ACE2 activity in affecting the viral activity and disease severity of SARS-CoV-2 is still an open question. Dipeptidyl peptidase-4 (DDP-4), a well-known anti-diabetic drug, has been widely used to control the glycemic condition in patients with diabetes. In this article, we are focusing on the impact of ACE inhibitors (ACEI) and DPP4 inhibitors used on SARS-CoV-2 activity and discussions about those drugs that may be related to infectious condition of COVID-19 diseases.

The role of dipeptidylpeptidase-4 inhibitors in the current therapy of type 2 diabetes mellitus

The role of dipeptidylpeptidase-4 inhibitors in the current therapy of type 2 diabetes mellitus

Peptide degradation and the role of DPP-4 inhibitors in the treatment of type 2 diabetes

Dipeptidyl peptidase-4 (DPP-4) inhibitors are now a widely used, safe and efficacious class of antidiabetic drugs, which were developed prospectively using a rational drug design approach based on a thorough understanding of the endocrinology and degradation of glucagon-like peptide-1 (GLP-1). GLP-1 is an intestinal hormone with potent insulinotropic and glucagonostatic effects and can normalise blood glucose levels in patients with type 2 diabetes, but the native peptide is not therapeutically useful because of its inherent metabolic instability. Using the GLP-1/DPP-4 system and type 2 diabetes as an example, this review summarises how knowledge of a peptide’s biological effects coupled with an understanding of the pathways involved in its metabolic clearance can be exploited in a rational, step-by-step manner to develop a therapeutic agent, which is effective and well tolerated, and any side effects are minor and largely predictable. Other peptides with metabolic effects which can also be degraded by DPP-4 will be reviewed, and their potential role as additional mediators of the effects of DPP-4 inhibitors will be assessed.

Translation of the clinical pharmacology findings into clinical practise; An example from the world of diabetes during the last two decades

The last two decades have witnessed the role of dipeptidyl peptidase-4 inhibitors (DPP-4i) in translation of the incretin-research science into clinically meaningful outcomes in management of type 2 diabetes (T2DM). The conceptual change shifted emphasis from a gluco-centric approach to holistic exploration of the underlying pathophysiological processes. This was conceivable as the discovery of glucagon like peptide-1 (GLP-1) in 1987 was followed by the understanding how DPP-4i's could prevent GLP-1 inactivation. The discovery of the world's first DPP-4i, DPP-728, and its pharmacologically improved version with optimised binding kinetics, vildagliptin, in 1998, lead to proof-of-concept studies establishing the prospect of DPP-4 inhibition in glycaemic control.

Potential role of dipeptidyl peptidase-4 inhibitors in atrial fibrillation

Potential role of dipeptidyl peptidase-4 inhibitors in atrial fibrillation

An updated systematic review and meta-analysis on the efficacy and tolerability of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes with moderate to severe chronic kidney disease.

Objective:This updated meta-analysis determines the effect of dipeptidyl peptidase-4 inhibitors on glycemic and tolerability outcomes in patients with type 2 diabetes mellitus and chronic kidney disease with glomerular filtration rate of ⩽60 mL/min or on dialysis.Methods:In all, 14 citations were identified from multiple databases. Qualitative assessments and quantitative analyses were performed.Results:There were 2261 participants, 49–79 years of age, 49% men and 44% Caucasians. In seven placebo-comparator studies, reduction in hemoglobin A1c at weeks 12–24 was 0.55% (95% confidence interval: −0.68 to −0.43), P < 0.00001). In three sulfonylurea-comparator studies, dipeptidyl peptidase-4 inhibitors did not significantly reduce hemoglobin A1c at weeks 52–54 (−0.15% (95% confidence interval: −0.32 to 0.02)). In one sitagliptin versus albiglutide study, albiglutide significantly reduced hemoglobin A1c in patients with moderate renal impairment (−0.51%). A similar reduction in hemoglobin A1c was seen with sitagliptin versus vildagliptin (−0.56% vs −0.54%). Compared with placebo or sulfonylurea, dipeptidyl peptidase-4 inhibitors did not significantly reduce hemoglobin A1c after 12 and 54 weeks in patients on dialysis. Hypoglycemia was reported by ~30% of patients in both dipeptidyl peptidase-4 inhibitors and placebo groups over 24–52 weeks. While hypoglycemia was more common with a sulfonylurea at 52–54 weeks (risk ratio: 0.46 (95% confidence interval: 0.18 to 1.18)), there was significant heterogeneity (I2 = 87%). Limitations included high drop-out rate from most studies and small number of active-comparator studies.Conclusions:Dipeptidyl peptidase-4 inhibitors in patients with chronic kidney disease caused a modest reduction in hemoglobin A1c versus placebo, but not when compared with sulfonylureas or albiglutide, or when used in patients on dialysis. Additional active-comparator studies are needed to further elucidate the role of dipeptidyl peptidase-4 inhibitors in patients with chronic kidney disease stages 3–5 or on dialysis.

Role of dipeptidyl peptidase-4 inhibitors in new-onset diabetes after transplantation

Despite strict pre- and post-transplantation screening, the incidence of new-onset diabetes after transplantation (NODAT) remains as high as 60%. This complication affects the risk of cardiovascular events and patient and graft survival rates. Thus, reducing the impact of NODAT could improve overall transplant success. The pathogenesis of NODAT is multifactorial, and both modifiable and nonmodifiable risk factors have been implicated. Monitoring and controlling the blood glucose profile, implementing multidisciplinary care, performing lifestyle modifications, using a modified immunosuppressive regimen, administering anti-metabolite agents, and taking a conventional antidiabetic approach may diminish the incidence of NODAT. In addition to these preventive strategies, inhibition of dipeptidyl peptidase-4 (DPP4) by the gliptin family of drugs has recently gained considerable interest as therapy for type 2 diabetes mellitus and NODAT. This review focuses on the role of DPP4 inhibitors and discusses recent literature regarding management of NODAT.

Linagliptin: DPP-4 Inhibition in the Treatment of Type 2 Diabetes Mellitus

The complex pathophysiologic mechanisms of type 2 diabetes are one of the barriers that make its treatment so difficult and it is also one of the responsible for the high prevalence of the disease around the world. Patients with T2DM have dysfunction in incretin hormones (such as glucagon-like peptide-1 or GLP-1 and glucose-dependent insulinotropic polypeptide or GIP). By inhibiting the dipeptidyl peptidase-4 (DPP-4) enzyme, it is possible to slow the inactivation of GLP-1 and GIP, promoting blood glucose level decrease in a glucose-dependent manner. Linagliptin is a dipeptidyl peptidase-4 inhibitor. This article reviews the pharmacology, mechanism of action, chemical structure, enzymatic binding, pharmacokinetics, pharmacodynamics, clinical trials, indications, contraindications and drug interactions of linagliptin and the role of DPP-4 inhibitors in the management of hyperglycemia in adults with T2DM. Linagliptin clinical trials showed clinical efficacy in decreasing glycated hemoglobin (HbA1c), fasting plasma glucose and postprandial glucose when administered as monotherapy or in combination with other oral antihyperglycemic agents (such as sulphonylureas, pioglitazone or metformin) and also insulin, including non-inferior efficacy versus sulphonylurea without weight gain. Adverse events are uncommon and may include upper respiratory tract infection, nasopharyngitis and headache. The risk of hypoglycemia with linagliptin is very low and is increased when the drug is combined with insulin or an insulin secretagogue drug, such as a sulphonylurea. Dose adjustments based on liver or renal function are not necessary with linagliptin use. Given its safety and efficacy profile, linagliptin is a valid treatment for patients with T2DM and is a particularly interesting option in patients with renal failure.

The Emerging Role of Dipeptidyl Peptidase-4 Inhibitors in Cardiovascular Protection: Current Position and Perspectives

Dipeptidyl peptidase-4 (DPP-4 or CD26) inhibitors, a new class of oral anti-hyperglycemic agents that prolong the bioavailability of the endogenously secreted incretin hormone glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic polypeptide (GIP), are effective in the treatment of diabetes. Accumulating data have indicated that DPP-4 inhibitors play important protective roles in the cardiovascular system. DPP-4 inhibitors act to decrease myocardial infarct size, stabilize the cardiac electrophysiological state during myocardial ischemia, reduce ischemia/reperfusion injury, and prevent left ventricular remodeling after myocardial infarction. Moreover, DPP-4 inhibitors can mobilize stem/progenitor cells to move to sites of cardiovascular injury, thus further promoting tissue repair. In addition, DPP-4 inhibitors not only improve myocardial metabolism but also regulate cardioactive peptides. DPP-4 inhibitors can also protect the vasculature through their anti-inflammatory and anti-atherosclerotic effects and through the ability of the inhibitors to promote vascular relaxation. Finally, the potential effects of DPP-4 inhibitors on blood pressure and lipid metabolism have also been investigated. However, some reports on the cardioprotective activities of DPP-4 inhibitors are controversial. Herein, we summarize the available data on cardiovascular protection by DPP-4 inhibitors that have emerged in recent years and discuss current position and future perspectives concerning the use of DPP-4 inhibitors in cardiovascular medicine.

Combination Therapy With DPP-4 Inhibitors and Insulin in Patients With Type 2 Diabetes Mellitus: What Is the Evidence?

As type 2 diabetes mellitus (T2DM) progresses, most patients will require insulin replacement therapy. Whether oral antidiabetic drug (OAD) therapy should be retained when initiating insulin is still debated. While the rationale to keep metformin with insulin is strong (mostly as an insulin-sparing agent to limit weight gain), the evidence is less clear for other OADs. In particular, the question now comes up what the expected benefit could be of combining the newer agents, such as the dipeptidyl peptidase-4 (DPP-4) inhibitors with insulin. Additionally, when metformin is no longer a treatment option, as in the case of patients with severe renal impairment, insulin is often used as monotherapy, with little evidence of benefit in maintaining other OADs. In this specific situation, it is also of interest to evaluate the potential benefit of combined treatment with a DPP-4 inhibitor and insulin. Among the classic limitations of insulin therapy in patients with T2DM, hypoglycemia remains a major barrier to glycemic control, along with weight gain exacerbation. The oral DPP-4 inhibitors improve glycemic control by increasing the sensitivity of the islet cells to glucose, and thus are not associated with an increased risk for hypoglycemia and are weight neutral. In addition to the expected benefits associated with limiting insulin dose and regimen complexity, the specific advantages the DPP-4 inhibitor drug class on hypoglycemia and weight gain could justify combining DPP-4 inhibitors with insulin; additionally, a DPP-4 inhibitor may be of special value to decrease glycemic excursions that are not properly addressed by basal insulin therapy and metformin use, even after optimizing titration of the basal insulin. However, given the common original perception that treatment with DPP-4 inhibitors may be less beneficial with increasing disease progression because of the loss of β-cell function, the potential relevance of these agents in the setting of advanced T2DM treated with insulin was not necessarily anticipated. Promising data from studies on the use of these new agents in insulin-treated patients with T2DM have started to emerge. Our article provides a comprehensive overview of the currently available evidence from controlled randomized clinical trials and we discuss the potential role of DPP-4 inhibitors in the this setting. Further clinical experience will allow to fully assess the positioning of these agents in insulin-treated T2DM populations.

DPP-4 inhibitors in the management of type 2 diabetes: A critical review of head-to-head trials

Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that DPP-4 inhibitors exert slightly less pronounced HbA(1c) reduction than metformin (with the advantage of better gastrointestinal tolerability) and similar glucose-lowering effects as with a thiazolidinedione (TZD; with the advantage of no weight gain). In metformin-treated patients, gliptins were associated with similar HbA(1c) reductions compared with a sulphonylurea (SU; with the advantage of no weight gain, considerably fewer hypoglycaemic episodes and no need for titration) and a TZD (with the advantage of no weight gain and better overall tolerability). DPP-4 inhibitors also exert clinically relevant glucose-lowering effects compared with a placebo in patients treated with SU or TZD (of potential interest when metformin is either not tolerated or contraindicated), and as oral triple therapy with a good tolerability profile when added to a metformin-SU or pioglitazone-SU combination. Several clinical trials also showed a consistent reduction in HbA(1c) when DPP-4 inhibitors were added to basal insulin therapy, with no increased risk of hypoglycaemia. Because of the complex pathophysiology of type 2 diabetes and the complementary actions of glucose-lowering agents, initial combination of a DPP-4 inhibitor with either metformin or a glitazone may be applied in drug-naive patients, resulting in greater efficacy and similar safety compared with either drug as monotherapy. However, DPP-4 inhibitors were less effective than GLP-1 receptor agonists for reducing HbA(1c) and body weight, but offer the advantage of being easier to use (oral instead of injected administration) and lower in cost. Only one head-to-head trial demonstrated the non-inferiority of saxagliptin vs sitagliptin. Clearly, more trials of direct comparisons between different incretin-based therapies are needed. Because of their pharmacokinetic characteristics, pharmacodynamic properties (glucose-dependent glucose-lowering effect) and good overall tolerability profile, DPP-4 inhibitors may have a key role to play in patients with renal impairment and in the elderly. The role of DPP-4 inhibitors in the therapeutic armamentarium of type 2 diabetes is rapidly evolving as their potential strengths and weaknesses become better defined mainly through controlled clinical trials.

Dipeptidylpeptidase-4 (DPP-4) inhibitors are favourable to glucagon-like peptide-1 (GLP-1) receptor agonists: Yes

The pharmacological treatment of type 2 diabetes (T2DM) is becoming increasingly complex, especially since the availability of incretin-based therapies. Compared with other glucose-lowering strategies, these novel drugs offer some advantages such as an absence of weight gain and a negligible risk of hypoglycaemia and, possibly, better cardiovascular and β-cell protection. The physician has now multiple choices to manage his/her patient after secondary failure of metformin, and the question whether it is preferable to add an oral dipeptidylpeptidase-4 (DPP-4) inhibitor (gliptin) or an injectable glucagon-like peptide-1 (GLP-1) receptor agonist will emerge. Obviously, DPP-4 inhibitors offer several advantages compared with GLP-1 receptor agonists, especially regarding easiness of use, tolerance profile and cost. However, because they can only increase endogenous GLP-1 concentrations to physiological (rather than pharmacological) levels, they are less potent to improve glucose control, promote weight reduction (“weight neutrality”) and reduce blood pressure compared to GLP-1 receptor agonists. Of note, none of the two classes have proven long-term safety and positive impact on diabetic complications yet. The role of DPP-4 inhibitors and GLP-1 receptor agonists in the therapeutic armamentarium of T2DM is rapidly evolving, but their respective potential strengths and weaknesses should be better defined in long-term head-to-head comparative controlled trials. Instead of trying to answer the question whether DPP-4 inhibitors are favourable to GLP-1 receptor agonists (or vice versa), it is probably more clinically relevant to look at which T2DM patient will benefit more from one or the other therapy considering all his/her individual clinical characteristics (“personalized medicine”).

How can we avoid the danger of hypoglycemia, one of the most serious complications of therapy of type 2 diabetes mellitus? The role of DPP-4 inhibitors

Optimal or near-optimal compensation of diabetes mellitus is almost inevitably fraught with the risk of hypoglycemia. In patients with type 2 diabetes (DM2), especially in those of old-age groups, the development of hypoglycemia increases the risk of CV death, cardiac rhythm disturbances, dementia, and depressive states. Whether absolutely all diabetic patients should be treated so as to ensure blood glucose levels close the physiological values thus far remains a matter of controversy. The results of large-scale clinical studies carried out in the recent years suggest the necessity to revise the existing algorithms for the treatment of patients with DM2. Highly efficacious agents for the purpose should be chosen with reference to both their glucose-normalizing activity and "the safety profile" (i.e. reduced risk of hypoglycemia). A panel of experts for the Russian Association of Endocrinologists (RAE) developed and published «Consensus Algorithm on the initiation and intensification of therapy of type 2 diabetes mellitus». Its main provisions emphasize the necessity of treating diabetics on an individual basis and establish target levels of glycemia for each patient. Special attention should be given to the patients belonging to high risk groups, i.e. those with manifest macrovascular pathology, unable to recognize hypoglycemia, and having serious concomitant diseases. The following first line preparations are recommended to enhance the safety of DM2 therapy: metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors and agonists of glucagon-like peptide-1 (GLP-1) receptors. The results of both national and international clinical studies of vildaglyptin give reason to recommend this DPP-4 inhibitor for a wider application to the treatment of patients with type 2 diabetes mellitus.

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

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. 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. 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. 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.

The Role of Dipeptidyl Peptidase-4 Inhibitors in the Management of Type 2 Diabetes

The Role of Dipeptidyl Peptidase-4 Inhibitors in the Management of Type 2 Diabetes

The Role of Dipeptidyl Peptidase-4 Inhibitors in the Management of Type 2 Diabetes

The Role of Dipeptidyl Peptidase-4 Inhibitors in the Management of Type 2 Diabetes