Efficacy Of Dipeptidyl Peptidase-4 Inhibitors Research Articles

Pharmacogenetics of dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes mellitus: A review

The review addresses publications on genetic polymorphisms that potentially impact the effectiveness of therapy with hypoglycemic drugs of the dipeptidyl peptidase-4 inhibitor group. The literature was searched in the PubMed database from 2017 to 2023. Polymorphisms of several genes (GLP1R, TCF7L2, DPP-4, KCNQ1, KCNJ11, PNPLA3, PRKD1) are associated with the pharmacokinetic values and efficacy of dipeptidyl peptidase-4 inhibitors, which may be promising for personalizing the treatment of patients with type 2 diabetes mellitus.

A Prospective Observational Study of Comparison, Safety, and Efficacy of Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Type 2 Diabetes Mellitus in A Tertiary Care Hospital

Aims: The purpose of the study was to determine the safety and efficacy of Dipeptidyl Peptidase 4-Inhibitor as mono-therapy and in combination therapy. The impact of age, disease duration and gender on the efficacy of DPP-4 inhibitors were also studied. Materials and Methods: A prospective observational study was conducted among patients with type 2 diabetes mellitus. The study consisted of 6 groups: Metformin+Glimepiride, Metformin+Teneligliptin, Glimepiride+Teneligliptin, Metformin only, Teneligliptin only and Glimepiride only. Fasting and Post Prandial Blood Sugar and HbA1c were monitored before and after 6 months of therapy. Results: In combination therapy, the adverse effects were higher in Glimepiride and Teneligliptin group followed by Metformin and Glimepiride and Metformin and Teneligliptin. The mean FBS reduction was 21.57 mg/dl, 28.32 mg/dl, and 20.08mg/dl in Metformin+Glimepiride, Metformin+Teneligliptin and Glimepiride+Teneligliptin, respectively. The mean Post-Prandial Blood Sugar reduction was 27.63mg/dl, 42.78mg/dl, 34.13mg/dl in Metformin+Glimepiride, Metformin+Teneligliptin and Glimepiride+Teneligliptin, respectively. The mean HbA1c reduction was 1.30%, 1.41%, and 0.80% in Metformin+Glimepiride, Metformin+Teneligliptin and Glimepiride+Teneligliptin, respectively. Conclusion: Metformin and Teneligliptin combination therapy and Teneligliptin monotherapy were safe and efficacious compared to all other oral hypoglycemic drugs under study. There was no significant impact of gender, BMI class and disease duration on the drug’s efficacy.

Safety and Efficacy of Di-Peptidyl Peptidase-4 Inhibitors in The Management of Inpatient Elderly with Type 2 Diabetes

Safety and Efficacy of Di-Peptidyl Peptidase-4 Inhibitors in The Management of Inpatient Elderly with Type 2 Diabetes

Decreased liver damage in rat models of short bowel syndrome through DPP4 inhibition.

Total parenteral nutrition causes liver damage in patients with short bowel syndrome (SBS), in whom intestinal failure-associated liver disease (IFALD) is the strongest risk factor for mortality. We previously demonstrated the efficacy of dipeptidyl peptidase-4 inhibitors (DPP4-Is) for nutritional absorption and intestinal barrier function enhancement. Herein, we investigated the efficacy of DPP4-Is in preventing liver damage in SBS rat models. Rats were allocated to one of five groups: normal saline (NS) + sham, DPP4-I + sham, NS + SBS, DPP4-I + SBS, and GLP-2 + SBS. DPP4-I or NS was administered orally once daily. Serum aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, and total bile acid levels were measured to assess liver function. Moreover, we evaluated liver damage using the SAF (steatosis activity fibrosis) score, which is also used to assess nonalcoholic steatohepatitis. ALT levels and SAF scores were significantly lower in the DPP4-I + SBS group than in the NS + SBS group. Jejunal and ileal villus heights were significantly higher in the DPP4-I + SBS group than in the GLP-2 + SBS group. The downregulation of ALT levels and SAF scores triggered by DPP4-I use may be correlated with DPP4-I-induced adiposis inhibition in SBS and NASH models. Therefore, DPP4-I may be used to reduce IFALD in patients with SBS.

Increasing Age Associated with Higher Dipeptidyl Peptidase-4 Inhibition Rate Is a Predictive Factor for Efficacy of Dipeptidyl Peptidase-4 Inhibitors.

Background It is not known which type 2 diabetes mellitus (T2DM) patients would most benefit from dipeptidyl peptidase-4 (DPP-4) inhibitor treatment. We aimed to investigate the predictors of response to DPP-4 inhibitors considering degree of DPP-4 inhibition.Methods This study is a post hoc analysis of a 24-week, randomized, double-blind, phase III trial that compared the efficacy and safety of a DPP-4 inhibitor (gemigliptin vs. sitagliptin) in patients with T2DM. Subjects were classified into tertiles of T1 <65.26%, T2=65.26%–76.35%, and T3 ≥76.35% by DPP-4 inhibition. We analyzed the change from baseline in glycosylated hemoglobin (HbA1c) according to DPP-4 inhibition with multiple linear regression adjusting for age, ethnicity, body mass index, baseline HbA1c, and DPP-4 activity at baseline.Results The mean age was greater in the high tertile group compared with the low tertile group (T1: 49.8±8.3 vs. T2: 53.1±10.5 vs. T3: 55.3±9.5, P<0.001) of DPP-4 inhibition. Although HbA1c at baseline was not different among tertiles of DPP-4 inhibition (P=0.398), HbA1c after 24-week treatment was lower in the higher tertile compares to the lower tertile (T1: 7.30%±0.88% vs. T2: 7.12%±0.78% vs. T3: 7.00%±0.78%, P=0.021). In multiple regression analysis, DPP-4 enzyme inhibition rate was not a significant determent for HbA1c reduction due to age. In subgroup analysis by tertile of DPP-4 inhibition, age was the only significant predictor and only in the highest tertile (R2=0.281, B=–0.014, P=0.024).Conclusion This study showed that HbA1c reduction by DPP-4 inhibitor was associated with increasing age, and this association was linked with higher DPP-4 inhibition.

In patients with type 2 diabetes the presence of Hashimoto's thyroiditis reduces the beneficial effect of dipeptidyl peptidase-4 inhibitor on plasma glucose control.

In this study, we compared the efficacy of a dipeptidyl peptidase-4 inhibitor (DPP4i) to improve glucose control in patients with type 2 diabetes mellitus (T2DM) with or without Hashimoto's thyroiditis (HT). First, we compared the change in glycated hemoglobin (HbA1c) between the hypothyroid condition (before levothyroxine sodium hydrate [LT4] treatment) and euthyroid condition (after LT4 treatment when patients had achieved euthyroidism for at least six months) in patients with T2DM and HT. Next, we compared the change in HbA1c levels before and six months of DPP4i treatment in patients with T2DM with and without HT. In hypothyroid condition the change in HbA1c after six months of DPP4i treatment was 0.13% ± 0.86%. The change in HbA1c levels from when patients first achieved euthyroidism to after six months in the euthyroid condition was 0.26% ± 0.90%. DPP4i efficacy in patients with T2DM and HT was reduced compared to patients with T2DM but without HT (-0.40 ± 0.90 vs. -0.99 ± 0.5, p = 0.0032). These data suggest that hypothyroidism does not impact on DPP4i efficacy. However, the effect of DPP4i in patients with T2DM and HT was reduced compared to that in T2DM patients without HT. An estimation of thyroid function before prescribing DPP4i may be useful tool for predicting the efficacy of DPP4i, allowing the ruling out complications from HT.

CD26/DPP4 Inhibitor: A Novel Prophylactic Drug for Chronic Allograft Dysfunction after Clinical Lung Transplantation

Prevention of chronic lung allograft dysfunction (CLAD) is still an issue. In mouse/rat lung transplantation (LTx) models, we have shown the efficacy of dipeptidyl peptidase 4 inhibitors (DPP4i), drugs for diabetes mellitus (DM). We assumed that the key mechanism might be stromal cell-derived factor-1 (SDF-1). This is a chemokine for regenerative stem cells to repair injured tissue, regarded as a direct injury marker. It is also induced by DPP4i to reinforce tissue repair. This study aims to elucidate the efficacy of DPP4i in clinical LTx, and to search for a new biomarker for CLAD or overall survival (OS). The patients who underwent cadaveric or living-donor LTx in our institution between 2002 and 2018 were retrospectively reviewed. Patients with DM were extracted and divided into two groups regarding the usage of DPP4i in perioperative periods. DPP4i therapy was based on the guideline for DM. SDF-1 and IL-10 in the serum samples in the 3rd and the 6th month after LTx were measured by ELISA. Patients' characteristics, postoperative outcomes, and the ELISA data were analyzed. Finally, we performed risk analyses for CLAD and OS. In a total of 95 LTx recipients with DM, 29 were treated with DPP4i, while 66 were not. 5-year CLAD-free survivals were 63% in the DPP4i group and 41% in the non-DPP4i group (p=0.044) (Figure). Other surgical outcomes were comparable. In three of four patients, SDF-1 levels increased after the initiation of DPP4i between the 3rd and the 6th month. In the evaluation of all, there was a positive correlation between IL-10 in the 6th month and SDF-1 in the 3rd month. According to the Cox regression model, the ratio of SDF-1 in the 6th month to the 3rd month was identified as the adverse prognostic factor for CLAD and OS. DPP4i may be a novel prophylactic drug for CLAD by inducing anti-inflammatory cytokine in LTx recipients with DM. The ratio of SDF-1 level in the 6th to the 3rd month may predict CLAD and OS. We will extend the research for non-DM patients as well.

Predictors of the Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Taiwanese Patients with Type 2 Diabetes Mellitus.

Background/purposeDipeptidyl peptidase-4 (DPP-4) inhibitors are the most popular oral antidiabetic drugs (OADs) in recent 20 years because of the low risk of hypoglycemia, intermediate efficacy to lower glycated hemoglobin (△HbA1c): 0.5–0.9%, neutral effect on body weight change, convenience for usage (mostly once daily), and rare occurrence of major side effects. The purpose of this study was to determine the important predictors of the efficacy of naïve use of DPP-4 inhibitors in Taiwanese patients with type 2 diabetes mellitus (T2D).MethodsA retrospective observational study was conducted. Of the T2D patients, 193 (122 men) naïve DPP-4 inhibitor users with an age of 58.0 ± 12.6 years, disease duration 5.4 ± 4.7 years, body mass index (BMI) 26.1 ± 4.3 kg/m2, and estimated glomerular filtration rate 95.9 ± 27.0 mL/min/1.73M2 were assessed for △HbA1c in 6 months.ResultsAfter 6 months of DPP-4 inhibitors use, mostly second or third line of OADs (2.8 ± 0.7 kinds of OADs), 193 T2D patients (mean baseline HbA1c: 8.4 ± 1.4%) had △HbA1c 1.1 ± 1.2% on average (P < 0.01). The group with a higher baseline HbA1c level had more effective efficacy (△HbA1c ≥0.5%) in lowering HbA1c. Single regression analysis showed that the change in HbA1c after 6 months of treatment was positively associated with the baseline HbA1c level (R = 0.71, P < 0.001). In addition, multiple regression analysis showed that contributors to decrease HbA1c level after 6 months were high baseline HbA1c level, low BMI, short T2D duration, and fewer kinds of OADs.ConclusionOur study suggested that high baseline HbA1c level, low BMI, short T2D duration, and fewer kinds of OADs are the predictors of the efficacy of DPP-4 inhibitors in Taiwanese patients with T2D. The baseline HbA1c level, in particular, played the most important role in effective efficacy (△HbA1c ≥0.5%).

4111Association of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors with cardiovascular events stratified by renal function: a network meta-analysis

Abstract Background Chronic kidney disease is a frequent co-morbidity in patients with diabetes and is associated with poor outcomes and elevated cardiovascular risk. Several novel oral antidiabetic therapies have been shown to be efficacious in reducing cardiovascular events. However, the impact of baseline renal function on cardiovascular efficacy is not well-established. Purpose To assess the cardiovascular efficacy of Dipeptidyl Peptidase-4 inhibitors (DPP-4i), Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) and Sodium-Glucose Cotransporter-2 inhibitors (SGLT-2i) stratified by renal function. Methods Cardiovascular outcome trials enrolling at least 1000 patients with type 2 diabetes for &gt;12 months' duration were included if they reported on a composite outcome of cardiovascular mortality, nonfatal myocardial infarction and nonfatal stroke and stratified outcome data by estimated glomerular filtration rate (eGFR) of &gt;60 mL/min/1.73m2 or &lt;60 mL/min/1.73m2. Studies enrolling patients with recent acute coronary events were excluded. Treatment and interaction effect estimates were aggregated by random-effects Bayesian network meta-analysis. Results 9 studies were included (2 DPP-4i; 4 GLP-1RA; 3 SGLT-2i), enrolling 92,626 patients accounting for 315,167 patient-years of follow-up. The eGFR was &lt;60 mL/min/1.73m2 in 21,302 patients (23.0%) and &gt;60 mL/min/1.73m2 in 71,324 patients (77.0%). The mean eGFR was 64.8 mL/min/1.73m2 in DPP-4i trials, 78.6 mL/min/1.73m2 in GLP-1RA trials and 78.6 mL/min/1.73m2 in SGLT-2i trials. Compared to placebo, DPP4i were not associated with reductions in the primary outcome (HR 1.00, 95% credible interval [CrI] 0.89–1.13). No reductions in the primary outcome were present for either strata of renal function (eGFR &gt;60: HR 1.00, 95% CrI 0.77–1.29; and eGFR &lt;60: HR 0.99, 95% CrI 0.81–1.20), with no significant interaction between renal function subgroups (interaction coefficient 1.00, 95% CrI 0.72–1.41). GLP-1RA were associated with reductions in the primary outcome overall (HR 0.85, 95% CrI 0.77–0.93). There was no significant interaction between renal function subgroups (eGFR &lt;60: HR 0.87, 95% CrI 0.70–1.06; and eGFR &gt;60: HR 0.83, 95% CrI 0.71–0.94; interaction coefficient 1.05, 95% CrI 0.83–1.35). Similarly, SGLT-2i were associated with reductions in the primary cardiovascular composite outcome (HR 0.88, 95% CrI 0.79–0.97), with no significant interaction between renal function subgroups (eGFR &lt;60: HR 0.82, 95% CrI 0.65–1.05; and eGFR &gt;60: HR 0.91, 95% CrI 0.78–1.06; interaction coefficient 0.92, 95% CrI 0.69–1.21). Conclusions Both SGLT-2i and GLP-RA are associated with reductions in a composite cardiovascular outcome with no evidence of interaction by renal function, while DPP-4i were not associated with reductions in events, with no evidence of interaction by renal function. These data suggest that cardiovascular efficacy of these medications is not affected by baseline renal status.

Effectiveness in clinical practice versus efficacy of dipeptidyl peptidase-4 inhibitors in clinical trials for type 2 diabetes: protocol for systematic review

IntroductionData supporting the use of oral antidiabetic drugs mainly rely on data from premarketing clinical trials. Real-world data studies are crucial to evaluate effectiveness of drugs. The aim of this...

Efficacy of anagliptin as compared to linagliptin on metabolic parameters over 2 years of drug consumption: A retrospective cohort study.

AIMTo evaluate the comparative effectiveness of anagliptin and linagliptin on the clinical parameters in patients with type 2 diabetes mellitus (T2DM).METHODSA 2-year retrospective cohort study was conducted in patients with T2DM who received anagliptin and linagliptin. We enrolled 234 patients (anagliptin group, 117 patients; linagliptin group, 117 patients).RESULTSThe glycemic control considerably improved 3, 6, 12, and 24 mo after the administration of both dipeptidyl peptidase-4 (DPP-4) inhibitors. Following the administration of anagliptin, the diastolic blood pressure and serum total cholesterol levels decreased. However, serum high-density lipoprotein cholesterol levels increased and urinary albumin-creatinine ratio decreased following linagliptin administration. Furthermore, the liver function improved after the administration of linagliptin.CONCLUSIONThese findings suggest that that the efficacy of DPP-4 inhibitors on the blood pressure, lipid profile, and liver function differs between anagliptin and linagliptin.

Safety and Efficacy of DPP4 Inhibitor and Basal Insulin in Type 2 Diabetes: An Updated Review and Challenging Clinical Scenarios.

The safety and efficacy of dipeptidyl peptidase-4 (DPP4) inhibitors as monotherapy or in combination with other oral antidiabetic agents or basal insulin are well established. DPP4 inhibitors stimulate glucose-dependent insulin secretion and inhibit glucagon production. As monotherapy, they reduce the hemoglobin A1c level by about 0.6–0.8%. The addition of a DPP4 inhibitor to basal insulin is an attractive option, because they lower both postprandial and fasting plasma glucose concentrations without increasing the risk of hypoglycemia or weight gain. The present review summarizes the extensive evidence on the combination therapy of DPP4 inhibitors and insulin-based regimens in patients with type 2 diabetes. We focus our discussion on challenging clinical scenarios including patients with chronic renal impairment, elderly persons and hospitalized patients. The evidence indicates that these drugs are highly effective and safe in the elderly and in the presence of mild, moderate and severe renal failure improving glycemic control with low risk of hypoglycemia. In addition, several randomized-controlled trials have shown that the use of DPP4 inhibitors in combination with basal insulin represents an alternative to the basal-bolus insulin regimen in hospitalized patients with type 2 diabetes.

Meta-analysis of HbA1c-Lowering Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Combination with Insulin in T2DM Patients

Randomized controlled trials (RCTs) have evaluated the efficacy of dipeptidyl peptidase-4 inhibitors (DPP-4i) as add-on therapy to insulin compared to insulin alone in T2DM patients, while there have been differences in the magnitude of the outcome effect across studies. This updated systematic review and meta-analysis aimed to evaluate the effect of DPP-4i in combination with insulin on HbA1c in T2DM patients. MEDLINE, EMBASE, and Cochrane databases were searched for RCTs that compared DPP-4i plus insulin to insulin alone for T2DM patients, with or without background therapy with other oral agents. The primary endpoint was the absolute change of HbA1c from baseline. Weighted mean difference (WMD) with 95% confidence intervals (CI) was calculated using a random effect model. The methodological quality of included RCTs was evaluated using the Cochrane risk of bias tool. Eighteen RCTs involving 6,493 patients with average follow-up of 32 weeks were identified and analyzed. DPP-4i plus insulin showed greater reduction in HbA1c than insulin alone (WMD -0.52%, 95% CI -0.61 to -0.43; P&amp;lt;0.0001) (Figure 1). In conclusion, compared with use of insulin alone, DPP-4i in combination with insulin can significantly lower HbA1c levels in T2DM patients. Further analysis is needed to better understand effects of this combination therapy on other outcomes, such as hypoglycemia and insulin. Disclosure J. Yang: None. Q. Tian: None. Y. Tang: Employee; Self; Merck &amp; Co., Inc.. Stock/Shareholder; Self; Merck &amp; Co., Inc.. Employee; Spouse/Partner; GlaxoSmithKline plc.. Stock/Shareholder; Spouse/Partner; GlaxoSmithKline plc. A.K. Shah: Employee; Self; Merck &amp; Co., Inc.. Stock/Shareholder; Self; Merck &amp; Co., Inc. R. Zhang: Employee; Self; Merck Sharp &amp; Dohme Corp. G. Chen: Employee; Self; Merck Sharp &amp; Dohme Corp.. Y. Zhang: None. S. Rajpathak: Employee; Self; Merck &amp; Co., Inc. T. Hong: Advisory Panel; Self; Novo Nordisk A/S, AstraZeneca.

Choosing Dipeptidyl Peptidase-4 Inhibitors, Sodium-glucose Cotransporter-2 Inhibitors, or Both, as Add-ons to Metformin: Patient Baseline Characteristics Are Crucial

PurposeType 2 diabetes remains a poorly managed disease, with only about half of individuals with type 2 diabetes meeting guideline-recommended glycosylated hemoglobin (HbA1C) targets. A major proportion of those who have not met HbA1C goals have an HbA1C <8.0% to 8.5%. In practice, it is quite common to have to decide between dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) as add-ons to metformin to help these individuals meet their HbA1C goals. This commentary reviews and provides guidance on how baseline factors can assist in the decision between the 2 classes or using both as add-ons to metformin. MethodsThe important clinical studies comparing the glycemic efficacy of DPP-4i versus SGLT2i or their combination as add-ons to metformin with a focus on the influence of baseline HbA1C on glycemic efficacy will be discussed and interpreted. The impact of estimated glomerular filtration rate and age on the glycemic efficacy of DPP-4i and SGLT2i will also be put into perspective. FindingsAt HbA1C <8.0% to 8.5%, HbA1C lowering is slightly greater with DPP-4i than with SGLT2i as an add-on to metformin; SGLT2i are associated with larger HbA1C improvements than DPP-4i at higher HbA1C levels. In cases of HbA1C ≥8.0%, dual DPP-4i-SGLT2i add-on therapy to metformin should be considered to help more patients achieve glycemic targets. The glycemic efficacy of SGLT2i, but not DPP-4i, declines with progressive renal insufficiency. In older adults, DPP-4i maintain their tolerability and efficacy, while SGLT2i may become less efficacious due to reduced renal function, and may be associated with higher rates of volume-related adverse effects. ImplicationsAlthough both DPP-4i and SGLT2i are effective add-on antihyperglycemic therapies to metformin monotherapy, baseline characteristics, such as HbA1C, renal function, and age, should be considered when choosing between the 2 classes to allow for optimal and timely diabetes management.

Dipeptidyl Peptidase-4 Inhibitors in Chronic Kidney Disease: A Systematic Review of Randomized Clinical Trials

Background: Chronic kidney disease (CKD) is common in patients with type 2 diabetes mellitus (T2DM) and limits therapeutic options. Dipeptidyl peptidase-4 (DPP-4) inhibitors represent a novel class of oral glucose-lowering agents and are known to be safe and effective in the general population. Methods: We searched Cochrane, EMBASE, and PubMed from the time of their inception until March 2015. We included randomized controlled trials analyzing the efficacy (change in hemoglobin A1C [HbA1C]) and safety of DPP-4 agents in individuals with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m²). We extracted study characteristics, participants' baseline characteristics, and safety outcomes from eligible studies. We performed a random effects meta-analysis to summarize the change in HbA1C and the relative risk of cardiovascular events in patients with T2DM and CKD. We also collected data on hypoglycemia, other serious adverse events, and mortality. Results: We reviewed 12 studies with 4,403 patients with CKD and 239 on dialysis, finding a mean weighted decline in HbA1C of -0.48 (95% CI -0.61 to -0.35) with DPP-4 inhibitor therapy compared to placebo. DPP-4 inhibitors did not result in any additional adverse events, hypoglycemic episodes, or increased mortality. Restricting to studies with low risk of bias did not alter these findings. Conclusions: DPP-4 inhibitors can lower HbA1C without increasing the risk of cardiovascular or other major adverse events in patients with CKD. Few studies reported critical adverse events such as heart failure and hypersensitivity. If compared with other oral antiglycemic drugs, the effect of DPP-4 inhibitors is limited; however, their low risk of hypoglycemia may favor their use in patients with CKD. Summary: This systematic review of DPP-4 inhibitors in CKD suggests that they reduce HbA1C by about 0.5%. Furthermore, there was not any increase in the risk for significant adverse events. More research is needed to determine the safety and efficacy of DPP-4 inhibitors in CKD.

The Glucose-lowering Efficacy of Sitagliptin in Obese Japanese Patients with Type 2 Diabetes.

Objective Dipeptidyl peptidase-4 (DPP-4) inhibitors are the most frequently prescribed oral hypoglycemic agents in Japan. Although a relationship between the efficacy of DPP-4 inhibitors and the body mass index (BMI) has been reported, this relationship is controversial. We investigated whether the BMI value affects the glucose-lowering efficacy of sitagliptin in obese Japanese patients with type 2 diabetes. Methods One hundred sixty-two outpatients with inadequate glycemic control were divided into four groups based on their baseline BMI values. They were then treated with sitagliptin (a DPP-4 inhibitor) for 3 months and followed-up for 12 months. Results Sitagliptin significantly reduced the hemoglobin A1c level (HbA1c: -0.71±0.55%) after 3 months, and continued to reduce the HbA1c level until 12 months. There was no significant difference in the efficacy of sitagliptin among the four BMI groups. A multiple linear regression analysis indicated that the factors contributing to the change in the HbA1c level were the baseline level of HbA1c and the homeostasis model assessment of β-cell function (HOMA-β). In terms of the relationship between the baseline BMI value and the efficacy of sitagliptin treatment, the number of patients who responded to sitagliptin treatment after 3 months was lowest in the group of patients with the highest BMI values. A multiple logistic regression analysis revealed that the baseline HOMA-β function and HbA1c level and a baseline BMI value of ≥30 kg/m2 significantly contributed to the response to sitagliptin treatment. Conclusion The results indicated that sitagliptin treatment was effective in controlling glucose metabolism disorder in obese Japanese patients with type 2 diabetes. However, the efficacy of sitagliptin treatment might be attenuated in severely obese patients, such as those with a BMI value of ≥30 kg/m2.

The Assessment of the Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Glucocorticoid-induced Diabetes by Continuous Glucose Monitoring.

Objective The administration of glucocorticoids usually causes a mild increase in fasting glucose levels and a greater dose-dependent increase in postprandial values in patients without pre-existing diabetes mellitus. Patients with persistent hyperglycemia due to glucocorticoid therapy sometimes require insulin therapy, which might result in increased weight gain and more episodes of hypoglycemia, some of which are severe. On the other hand, scant evidence is available on the efficacy of oral hypoglycemic agents in treating glucocorticoid-induced diabetes. In this study, we evaluated the efficacy of dipeptidyl peptidase (DPP)-4 inhibitors in patients with glucocorticoid-induced diabetes by continuous glucose monitoring (CGM). Methods We examined the glycemic profiles using CGM at baseline and 1-4 weeks after initiating DPP-4 inhibitor treatment in patients with newly developed glucocorticoid-induced diabetes. Results Eleven patients who had been diagnosed with kidney disease or other diseases with renal involvement were recruited for the present retrospective study. After starting DPP-4 inhibitors, the mean and standard deviation (SD) of the glucose level, and the mean amplitude of glycemic excursion (MAGE) were significantly improved in comparison to baseline. Furthermore, the area over the curve (AOC) for the glucose levels <70 mg/dL was not increased in comparison to baseline after the initiation of DPP-4 inhibitor treatment. The results indicate that the treatment of patients with glucocorticoid-induced diabetes using DPP-4 inhibitors can minimize the risk of hypoglycemia and reduce glucose variability. Conclusion DPP-4 inhibitors are potentially useful for blood glucose control in patients with glucocorticoid-induced diabetes.

Factors Related to the Glucose-Lowering Efficacy of Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review and Meta-Analysis Focusing on Ethnicity and Study Regions.

Several systematic reviews and meta-analyses have been conducted including an analysis to investigate the difference between ethnic groups in the glucose-lowering efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors. This study assessed the factors related to the glucose-lowering efficacy and explored potential differences among ethnicities; in particular, Japanese subjects were dealt separately from other Asian subjects. A systematic literature search was conducted using the MEDLINE, EMBASE, Cochrane Central Register, Japan Medical Abstracts Society, and ClinicalTrials.gov databases. Electronically searchable study results from the US/EU/Japanese regulatory approval reviews were also used. The weighted mean difference (WMD) for glycosylated hemoglobin (HbA1c) change from baseline in DPP-4 inhibitors compared with placebo was calculated. Heterogeneity was assessed by using the Q statistic and I 2 statistic. Univariate and multivariate meta-regression analyses were performed. The literature search identified 79 studies with 91 arms and 25,095 patients. The WMD in the change from baseline of HbA1c between the DPP-4 inhibitor group and placebo group was -0.695% (95% confidence interval -0.734 to -0.656) with considerable heterogeneity (I 2=69.7%). In univariate meta-regression, factors including study duration, percentage of males, age, duration of diabetes mellitus, baseline HbA1c values, body mass index, body weight, and percentage of Asian subjects showed associations with the glucose-lowering efficacy. Additionally, studies in Asian subjects, studies in Japanese subjects, and studies conducted in Japan showed relations when three classifications regarding ethnicity and study regions were applied. In multivariate meta-regression, studies in Japanese subjects/studies conducted in Japan as well as the baseline HbA1c values were identified as influencing factors. These identified factors-Japanese subjects/studies conducted in Japan and the baseline HbA1c values-should be taken into account when planning and conducting future clinical studies.

Inter-regulation of gastric emptying and incretin hormone secretion: implications for postprandial glycemic control.

The GI tract is central to the regulation of postprandial glycemia, with the rate of gastric emptying and the secretion of the incretin hormones, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, being key determinants. Gastric emptying exhibits a large interindividual variation; the latter not only accounts for differences in postprandial glycemia but also determines postprandial incretin profiles. Accordingly, the rate of gastric emptying may affect the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors. In contrast, glucagon-like peptide-1 receptor agonists lower postprandial glycemia predominantly by their action to slow gastric emptying. This review discusses the inter-relationship between gastric emptying and the incretin axis in the context of changes in blood glucose, with an emphasis on the relevant clinical implications.

Safety and efficacy of dipeptidyl peptidase-4 inhibitors vs sulfonylurea in metformin-based combination therapy for type 2 diabetes mellitus: Systematic review and meta-analysis.

The purpose of this study was to compare the safety and efficacy of DPP-4 inhibitors versus sulfonylurea as adjunctive second-line therapy in patients with type 2 diabetes mellitus, inadequately controlled with metformin mono-therapy. A systematic review of published randomized controlled trials (RCTs) was performed in MEDLINE, EMBASE, PubMed and Cochrane library. Two reviewers independently selected the studies, extracted the data and assessed the risk of bias. Clinical outcomes were cardiovascular events, HbA1c % change from baseline, body weight and hypoglycemic event rate. A direct comparison meta-analysis using a random effect model was conducted to calculate mean differences in treatment effects and risk ratio between DPP-4 inhibitors and sulfonylurea. Ten RCTs on adult patients with type 2 diabetes and inadequate glycemic control were included in the final analysis. DPP-4 inhibitors compared to sulfonylureas produced a non-significant difference in HbA1c% change in 10,139 subjects, whereas a significant decrease in the rate of hypoglycemic events was observed in favor of DPP-4 inhibitors (RR= 0.12; P<0.00001) involving 10,616 patients, with at least one hypoglycemic event during the follow-up period (12-104 weeks). Body weight decreased by 2.2 kg (95% CI 1.7-2.7) with DPP-4 inhibitors, compared with sulfonylureas. There were insufficient data to assess a difference in the risk for cardiovascular events. The review shows that, in terms of clinical efficacy, there is no significant difference between DPP4-inhibitors and sulfonylurea when either is added to metformin mono-therapy. In contrast, the safety assessment analysis showed a significant decrease in the risk of hypoglycemic events in patients using DPP4-inhibitors.