sitagliptin-phosphate and Hypoglycemia

Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset diabetes. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. This is an update of a review first published in 2017.. To evaluate the efficacy and safety of glucose-lowering agents for treating pre-existing and new onset diabetes in people who have undergone kidney transplantation.. We searched the Cochrane Kidney and Transplant Register of Studies up to 16 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.. All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion.. Four authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI).. Ten studies (21 records, 603 randomised participants) were included - three additional studies (five records) since our last review. Four studies compared more intensive versus less intensive insulin therapy; two studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; one study compared DPP-4 inhibitors to insulin glargine; one study compared sodium glucose co-transporter 2 (SGLT2) inhibitors to placebo; and two studies compared glitazones and insulin to insulin therapy alone. The majority of studies had an unclear to a high risk of bias. There were no studies examining the effects of biguanides, glinides, GLP-1 agonists, or sulphonylureas. Compared to less intensive insulin therapy, it is unclear if more intensive insulin therapy has an effect on transplant or graft survival (4 studies, 301 participants: RR 1.12, 95% CI 0.32 to 3.94; I. The efficacy and safety of glucose-lowering agents in the treatment of pre-existing and new-onset diabetes in kidney transplant recipients is questionable. Evidence from existing studies examining the effect of intensive insulin therapy, DPP-4 inhibitors, SGLT inhibitors and glitazones is mostly of low to very low certainty. Appropriately blinded, larger, and higher quality RCTs are needed to evaluate and compare the safety and efficacy of contemporary glucose-lowering agents in the kidney transplant population.

Topics: Adamantane; Bias; Cause of Death; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Fasting; Glycated Hemoglobin; Graft Survival; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Kidney Transplantation; Nitriles; Pioglitazone; Postoperative Complications; Pyrrolidines; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones; Transplant Recipients; Vildagliptin

The purpose of this study was to assess the efficacy and hypoglycemic risk of sitagliptin versus that of GLP-1 receptor agonists in the management of obese/overweight patients with T2DM.. EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov were searched; randomized controlled trials comparing the efficacy of sitagliptin versus that of GLP-1 receptor agonists in obese/overweight patients with T2DM were included. The mean BMI of participants for each study was ≥30 kg/m. We conducted a meta-analysis according to the methods specified in the Cochrane Handbook for Systematic Reviews of Interventions. RevMan 5.1 software was used to perform the meta-analysis. The Cochrane Q test and I statistics were used to estimate the heterogeneity among studies. The results are expressed as the mean difference (MD) or risk ratio (RR) with 95% confidence intervals.. A total of 8 eligible studies were included in our meta-analysis. Compared with GLP-1 receptor agonists, sitagliptin was less effective at reducing HbA1c (0.42 [0.27, 0.56]), FPG (0.78 [0.36, 1.19]), PPG (2.61 [1.35, 3.87]), and body weight (1.42 [0.71, 2.14]). Conversely, there were no significant differences in SBP reduction (0.38 [-1.14, 1.89]), DBP reduction (-0.30 [-1.00, 0.39]), and hypoglycemic risk (1.09 [0.50, 2.35]).. For obese/overweight patients, sitagliptin may exert a less potent effect on HbA1C, FPG, PPG, and weight reduction than GLP-1 receptor agonists, but these drugs had a similar efficacy in reducing blood pressure; furthermore, there was no significant difference in hypoglycemic risk.

Topics: Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemia; Hypoglycemic Agents; Obesity; Sitagliptin Phosphate

To improve understanding of the safety and efficacy of adding sitagliptin to treatment of patients with type 2 diabetes taking premixed insulin, data from patients using premixed insulin ± metformin (screening HbA1c ≥7.5% and ≤11%) in either of two clinical trials in which sitagliptin 100 mg once-daily or placebo was added to various formulations of insulin treatment, were analysed. In both trials, insulin doses were to remain stable throughout the 24-week trial period. At week 24, the between-group difference (sitagliptin - placebo) in the least squares mean (95% confidence intervals) change from baseline in HbA1c in patients using premixed insulin was -0.43% (-0.58, -0.28), P <0.001. Adverse events were generally similar between the treatment groups. The incidence of symptomatic hypoglycaemia was slightly higher with sitagliptin, and the incidence of hypoglycaemia requiring medical attention was slightly higher with placebo; in both cases the difference was not statistically significant. The data from this pooled analysis confirm the utility of sitagliptin used in combination with premixed insulin in patients with type 2 diabetes.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Incidence; Insulin; Male; Metformin; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Retrospective Studies; Sitagliptin Phosphate; Treatment Outcome

Glucagon-like peptide-1 (GLP-1) receptor agonists are highly potent antihyperglycemic drugs that impose low risk of hypoglycemia and also result in body weight reduction. Currently, all approved members of the class require administration by injection. Areas covered: This manuscript reviews oral semaglutide-an experimental GLP-1 receptor agonist in phase-3 clinical development. Available pharmacological and clinical data of the drug are reviewed, and important end-points described. Expert opinion: Oral peptide delivery has become possible with the discovery of absorption enhancers. The clinical development program of once-daily oral semaglutide has shown superiority in reducing glycosylated hemoglobin and body weight in comparison with placebo and active comparators (sitagliptin, liraglutide, and empagliflozin). Safety and tolerability of oral semaglutide is in line with injectable members of the class. Delayed gastric emptying, local increase in pH, and enhanced absorption do not seem to affect the exposure of a number of other oral drugs that have been tested (metformin, digoxin, oral contraceptive ethinylestradiol/levonorgestrel, lisinopril, warfarin, furosemide and rosuvastatin). Clinical questions for further investigation include the effectiveness and safety of oral semaglutide in cardiovascular indications.

Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Glucosides; Humans; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Sitagliptin Phosphate

This article reviews evidence supporting sodium glucose cotransporter 2 (SGLT2) inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor combination therapy for management of type 2 diabetes mellitus (T2DM).. We conducted a nonsystematic review of the literature focusing on single-pill or fixed-dose combinations of SGLT2 inhibitors and DPP-4 inhibitors available in the United States.. SGLT2 inhibitors and DPP-4 inhibitors have complementary mechanisms of action that address several of the underlying pathophysiologic abnormalities present in T2DM without overlapping toxicities. The combination of these 2 agents has several advantages including a low risk of hypoglycemia, the potential for weight loss, the ability to coformulate into a pill with once-daily administration, and the possibility to use with other classes of glucose-lowering agents. Cardiovascular outcomes trials reported to date support the safety of the DPP-4 class and suggest possible cardioprotective effects for SGLT2 inhibitors - at least based on the first reported study that used empagliflozin. Recent clinical evidence shows that SGLT2 inhibitor/DPP-4 inhibitor therapy is an effective combination for T2DM treatment, providing glycated hemoglobin (HbA1c) reductions of 1.1 to 1.5%, and weight reductions of approximately 2 kg when added to metformin, which is its primary place in therapy.. The combination of an SGLT2 inhibitor/DPP-4 inhibitor is a safe and effective treatment choice for patients with T2DM who are unable to obtain adequate glycemic control with metformin therapy, cannot use metformin, or have a higher baseline HbA1c.. BP = blood pressure; CI = confidence interval; CVOT = cardiovascular outcomes; DKA = diabetic ketoacidosis; DPP-4 = dipeptidyl peptidase-4; EXAMINE = EXamination of cArdiovascular outcoMes with alogliptiN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome; FDA = Food and Drug Administration; HbA1c = glycated hemoglobin; HR = hazard ratio; MACE = major adverse cardiovascular events; SAVOR-TIMI 53 = Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Type 2 Diabetes Mellitus; SBP = systolic blood pressure; SGLT2 = sodium glucose cotransporter 2; TECOS = Trial to Evaluate Cardiovascular Outcomes after Treatment with Sitagliptin; T2DM = type 2 diabetes mellitus; XR = extended release.

Topics: Adamantane; Benzhydryl Compounds; Blood Glucose; Canagliflozin; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glucosides; Humans; Hypoglycemia; Hypoglycemic Agents; Linagliptin; Metformin; Piperidines; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome; Uracil

To compare the effectiveness of dulaglutide 1.5 and 0.75 mg with active comparators and placebo with regard to a composite endpoint of glycated haemoglobin (HbA1c), weight and hypoglycaemia, using post hoc analyses.. A logistic regression analysis was performed on the intention-to-treat population, using data from the last observation carried forward, and the composite endpoint of HbA1c <7.0% (53 mmol/mol), no weight gain (≤0 kg) and no hypoglycaemia (glucose <3.0 mmol/l or severe hypoglycaemia) after 26 weeks for each trial in the AWARD programme separately.. At 26 weeks, within each study, 37-58% of patients on dulaglutide 1.5 mg, 27-49% of patients on dulaglutide 0.75 mg, and 9-61% of patients on active comparators achieved the composite endpoint. Significantly more patients reached the composite endpoint with dulaglutide 1.5 mg than with metformin, sitagliptin, exenatide twice daily or insulin glargine: odds ratio (OR) 1.5 [95% confidence interval (CI) 1.0, 2.2; p < 0.05], OR 4.5 (95% CI 3.0, 6.6; p < 0.001), OR 2.6 (95% CI 1.8, 3.7; p < 0.001) and OR 7.4 (95% CI 4.4, 12.6; p < 0.001), respectively, with no difference between dulaglutide 1.5 mg and liraglutide 1.8 mg. In addition, significantly more patients reached the composite endpoint with dulaglutide 0.75 mg than with sitagliptin or insulin glargine: OR 3.3 (95% CI 2.2, 4.8; p < 0.001) and OR 4.5 (95% CI 2.7, 7.8; p < 0.001), respectively.. Dulaglutide is an effective treatment option, resulting in a similar or greater proportion of patients reaching the HbA1c target of <7.0% (53 mmol/mol), without weight gain or hypoglycaemia compared with active comparators.

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide; Female; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Liraglutide; Male; Metformin; Middle Aged; Peptides; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Sitagliptin Phosphate; Treatment Outcome; Venoms; Weight Gain

A meta-analysis was conducted to assess the clinical efficacy and safety of dulaglutide in patients with type 2 diabetes mellitus (T2DM). Medline, Embase, Cochrane Library and www. clinicaltrials. gov (up to February 15(th), 2015) were searched. Randomized controlled trials comparing dulaglutide to other drugs for T2DM were collected. Twelve RCTs were included, and the overall bias was low. As the monotherapy, compared with control (placebo, metformin and liraglutide), dulaglutide resulted in a significant reduction in HbA1c (WMD, -0.68%; 95% CI, -0.95 to -0.40), FPG (WMD, -0.90 mmol/L; 95% CI, -1.28 to -0.52), a similar risk of hypoglycemia (7.8% vs. 10.6%), less body weight loss (WMD, 0.51 kg; 95% CI, 0.27 to 0.75). As an add-on intervention with oral antihyperglycemic medication (OAM) and insulin, compared with control (placebo, sitagliptin, exenatide, liraglutide and glargine), dulaglutide lowered HbA1c (WMD, -0.51%; 95% CI, -0.68 to -0.35) and body weight significantly (WMD, -1.30 kg, 95% CI, -1.85 to -1.02) notably, and elicited a similar reduction in FPG (WMD, -0.19 mmol/L; 95% CI, -1.20 to 0.82), an similar incidence of hypoglycemia (24.5% vs. 24.5%). This meta-analysis revealed the use of dulaglutide as a monotherapy or an add-on to OAM and lispro appeared to be effective and safe for adults with T2DM.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Insulin; Insulin Glargine; Liraglutide; Metformin; Patient Safety; Peptides; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Sitagliptin Phosphate; Treatment Outcome; Venoms

Hypoglycemia is the most common side effects for most glucose-lowering therapies. It constitutes a serious risk that faces diabetic patients who fast during Ramadan (the 9th month in the Islamic calendar). New glucose-lowering classes like dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonist (GLP-1 RA), and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are efficacious in controlling blood glucose level with less tendency to induce hypoglycemia and thus may constitute a good choice for diabetic patients during Ramadan. This study reviews the safety and efficacy of newer glucose-lowering therapies during Ramadan. This study was accomplished through a careful literature search about studies that assess the benefit and side effects of these new glucose-lowering therapies during Ramadan during September 2015. Vildagliptin, sitagliptin, liraglutide, exenatide, and dapagliflozin were the only studied glucose-lowering therapies. All of the studied newer glucose-lowering therapies except dapagliflozin were associated with reduced risk to induce hypoglycemia. Gastrointestinal upset was common with the usage of liraglutide while increased thirst sensation was common with dapagliflozin. In conclusion DPP-4 inhibitors such as vildagliptin and sitagliptin may form a suitable glucose-lowering therapy option for Ramadan fasting patients.

Topics: Adamantane; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Exenatide; Fasting; Glucagon-Like Peptide-1 Receptor; Glucosides; Holidays; Humans; Hypoglycemia; Hypoglycemic Agents; Islam; Liraglutide; Nitriles; Peptides; Pyrrolidines; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Venoms; Vildagliptin

The purpose of this study was to review the current literature and information on the combination product Juvisync™ (sitagliptin + simvastatin), which was approved by the US Food and Drug Administration in October 2011.. PubMed (2001-2014) was searched for primary and review articles on sitagliptin, simvastatin, or the combination product. Drug manufacturing data and product labeling were also used. Studies of simvastatin, sitagliptin, or the combination were screened and analyzed to include relevant and recent papers. Selected English language trials were limited to those with human subjects and included both safety and efficacy outcomes.. When compared with glipizide as add-on therapy to metformin, sitagliptin was noninferior but had lower rates of hypoglycemia and weight gain. In addition, when compared with insulin glargine, sitagliptin was less effective in decreasing glycosylated hemoglobin, but was associated with significantly lower rates of hypoglycemia. Further, trials have shown a beneficial effect of using statins in patients with diabetes mellitus with regard to decreasing cardiovascular risk, regardless of baseline lipid levels or the presence of a cardiac disease. Both medications have also demonstrated an acceptable side effect profile. However, caution is needed when coadministering with any drug that may increase simvastatin levels to reduce the risk of myopathy and rhabdomyolysis.. Juvisync should be used in patients requiring both sitagliptin and simvastatin. Both agents have shown good efficacy and acceptable safety profiles. Sitagliptin is a good option for diabetic patients to improve glycemic control with a lower risk of hypoglycemia and weight gain.

Topics: Biomarkers; Blood Glucose; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Combinations; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypoglycemia; Polypharmacy; Pyrazines; Risk Factors; Simvastatin; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Weight Gain

To determine which non-insulin glucose-lowering treatment regimens are most appropriate in people with type 2 diabetes who choose to fast during Ramadan.. Electronic databases were searched for randomized controlled trials (RCTs) and observational studies that compared non-insulin glucose-lowering agents in people with type 2 diabetes fasting during Ramadan. Those studies which reported hypoglycaemia, weight and glycated haemoglobin (HbA1c) change were included. Data were pooled using random effects models.. A total of 16 studies were included: 9 RCTs and 7 observational studies. There was evidence that dipeptidyl peptidase-4 (DPP-4) inhibitors led to fewer hypoglycaemic events compared with sulphonylureas. Sitagliptin significantly reduced the number of patients with ≥1 hypoglycaemic episodes during Ramadan [risk ratio (RR) 0.48, 95% confidence interval (CI) 0.36, 0.64; p > 0.0001]. This was not replicated in the RCTs of vildagliptin, but a significant reduction was found in the observational studies (RR 0.28, 95% CI 0.10, 0.75; p = 0.01) with high heterogeneity (I(2)  = 86.7%). Significant reductions in HbA1c and weight were seen in the observational studies of vildagliptin versus sulphonylureas. The use of liraglutide led to significant weight loss (-1.81 kg, 95% CI -2.91, -0.71; p = 0.001) compared with sulphonylureas. Pioglitazone significantly increased weight compared with placebo (3.48 kg, 95% CI 2.82, 4.14; p < 0.0001).. The analysis supports the use of DPP-4 inhibitors during Ramadan rather than sulphonylureas for reduction in hypoglycaemia without a cost to diabetes control and weight. The glucagon-like peptide (GLP)-1 agonist liraglutide provides clinical benefits, but more studies are required. RCTs of DPP-4 inhibitors compared with GLP-1 agonists and novel therapies including the sodium-glucose co-transporter 2 and α-glucosidase inhibitors are needed to inform evidence-based guidelines.

Topics: Adamantane; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Holidays; Humans; Hypoglycemia; Hypoglycemic Agents; Islam; Liraglutide; Nitriles; Observational Studies as Topic; Pioglitazone; Pyrrolidines; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Sulfonylurea Compounds; Thiazolidinediones; Vildagliptin; Weight Loss

Sitagliptin, a dipeptidyl peptidase 4 inhibitor, was the first in its class to receive approval from the US FDA in 2006 for the treatment of Type 2 diabetes mellitus. It has been evaluated in numerous clinical trials and has several attractive features as an antidiabetic agent, including a low risk for hypoglycemia, a neutral effect on weight, and an ability to be used in chronic kidney disease and more. This article provides an up-to-date discussion of the pharmacokinetics/pharmacodynamics, clinical efficacy, safety and tolerability of sitagliptin.

Topics: Animals; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Approval; Humans; Hypoglycemia; Hypoglycemic Agents; Sitagliptin Phosphate; United States; United States Food and Drug Administration

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.

Topics: Adamantane; Body Weight; Diabetes Complications; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Disease Progression; Drug Therapy, Combination; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Linagliptin; Nitriles; Piperidines; Purines; Pyrazines; Pyrrolidines; Quinazolines; Renal Insufficiency, Chronic; Sitagliptin Phosphate; Triazoles; Uracil; Vildagliptin

The presence of cardiovascular disease (CVD) in Type 1 diabetes largely impairs life expectancy. Hyperglycemia leading to an increase in oxidative stress is considered to be the key pathophysiological factor of both micro- and macrovascular complications. In Type 1 diabetes, the presence of coronary calcifications is also related to coronary artery disease. Cardiac autonomic neuropathy, which significantly impairs myocardial function and blood flow, also enhances cardiac abnormalities. Also hypoglycemic episodes are considered to adversely influence cardiac performance. Intensive insulin therapy has been demonstrated to reduce the occurrence and progression of both micro- and macrovascular complications. This has been evidenced by the Diabetes Control and Complications Trial (DCCT) / Epidemiology of Diabetes Interventions and Complications (EDIC) study. The concept of a metabolic memory emerged based on the results of the study, which established that intensified insulin therapy is the standard of treatment of Type 1 diabetes. Future therapies may also include glucagon-like peptide (GLP)-based treatment therapies. Pilot studies with GLP-1-analogues have been shown to reduce insulin requirements.

Topics: Antihypertensive Agents; Autonomic Nervous System Diseases; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Neuropathies; Drug Therapy, Combination; Exenatide; Exercise Therapy; Glucagon-Like Peptide 1; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemia; Hypoglycemic Agents; Insulin; Oxidative Stress; Peptides; Pyrazines; Sitagliptin Phosphate; Triazoles; Venoms

The ever-increasing burden of type 2 diabetes mellitus (T2DM) and inadequate control in the majority of patients has led to a quest for newer therapeutic options. There have been recent exciting advances in the treatment of T2DM, targeting the enteroinsular axis with incretin-based therapies that include the dipeptidyl peptidase IV (DPP-IV) inhibitors.. The background, pharmacodynamic and pharmacokinetic profile of sitagliptin and important clinical trials with this drug are discussed in this paper. This review is intended to provide a comprehensive overview of the DPP-IV inhibitor sitagliptin, its clinical use and an expert opinion about its place in the treatment algorithm of diabetes management.. Sitagliptin is a well-tolerated, moderately efficacious, weight-neutral oral antidiabetic agent, with a low incidence of hypoglycemia. It may have a particular role in the management of diabetic patients with kidney or liver dysfunction. Animal studies indicate a protective effect on the pancreatic beta cell, thus limiting the progression of the disease, but this remains to be proven in humans.

Topics: Administration, Oral; Algorithms; Animals; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypoglycemia; Hypoglycemic Agents; Pyrazines; Sitagliptin Phosphate; Triazoles

Topics: Adamantane; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Hypoglycemic Agents; Incretins; Nitriles; Pyrazines; Pyrrolidines; Sitagliptin Phosphate; Triazoles; Vildagliptin

A systematic review of the literature, in combination with a meta-analysis of randomized controlled trials comparing treatments with placebo, was conducted to provide an update on the clinical efficacy and safety of incretin-based medications in adult patients with type 2 diabetes.. A literature search (2000-2009) identified 38 placebo-controlled trials (phase II or later - parallel design) comparing exenatide (n = 8), liraglutide (n = 7), vildagliptin (n = 11) and sitagliptin (n = 12) with placebo. Outcomes were change from baseline in HbA(1c) and in weight, and the number of patient-reported hypoglycemic episodes. HbA(1c) and weight outcomes were analyzed as weighted mean differences (WMD), and the number of hypoglycemic episodes as relative risks (RR).. Patients receiving liraglutide showed greater reduction in HbA(1c) in comparison to placebo (WMD = -1.03, 95% confidence interval, CI = -1.16 to -0.90, p < 0.001) than those on sitagliptin (WMD = -0.79, 95% CI = -0.93 to -0.65, p < 0.001), exenatide (WMD = -0.75, 95% CI = -0.83 to -0.67, p < 0.001) or vildagliptin (WMD = -0.67, 95% CI = -0.83 to -0.52, p < 0.001). Weight was statistically significantly negatively associated with exenatide (WMD = -1.10, 95% CI = -1.32 to -0.87, p < 0.001) and positively associated with sitagliptin (WMD = 0.60, 95% CI = 0.33-0.87, p < 0.001) and vildagliptin (WMD = 0.56, 95% CI = 0.27-0.84, p < 0.001). The number of patient-reported hypoglycemic episodes was statistically significantly associated with the use of sitagliptin (RR = 2.56, 95% CI = 1.23-5.33, p = 0.01) and exenatide (RR = 2.40, 95% CI = 1.30-4.11, p = 0.002).. Incretin-based therapies are effective in glycemic control and also offer other advantages such as weight loss (exenatide and liraglutide). This may have an important impact on patient adherence to medication.

Topics: Adamantane; Adult; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Exenatide; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Nitriles; Peptides; Pyrazines; Pyrrolidines; Sitagliptin Phosphate; Triazoles; Venoms; Vildagliptin; Weight Loss

Type 2 diabetes is typically associated with insulin resistance and dysfunction of insulin-secreting pancreatic beta-cells. Addressing these defects often requires therapy with a combination of differently acting antidiabetic agents. A potential novel combination in development brings together the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin with the thiazolidinedione pioglitazone into a fixed-dose single-tablet combination. The former component acts mainly to increase prandial insulin secretion; the latter improves insulin sensitivity.. To date, clinical trials conducted in type 2 diabetes patients have used combinations of sitagliptin (100 mg/day) and pioglitazone (30 - 45 mg/day) as separate tablets. These trials have shown that the combinations offer additive efficacy in reducing blood glucose when given as initial antidiabetic therapy and as add-on therapy when pioglitazone alone fails to maintain glycemic control.. Initial therapy with a combination of sitagliptin (100 mg/day) and pioglitazone (30 mg/day) reduced HbA1c by > 2% starting from a baseline > 9%. Adding sitagliptin (50 - 100 mg/day) to patients inadequately controlled on pioglitazone reduced HbA1c by 0.7 - 1.4% from a baseline of 8 - 8.5%. The combination did not increase the risk of hypoglycemia and produced similar or slightly more weight gain than pioglitazone alone when introduced as initial antidiabetic therapy.. The combination of sitagliptin and pioglitazone was well tolerated in these trials, and would appear to be suited to a fixed-dose single-tablet combination for once-daily administration.

Topics: Animals; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Resistance; Male; Pioglitazone; Pyrazines; Sitagliptin Phosphate; Thiazolidinediones; Triazoles

After metformin, with insulin in patients with severe hyperglycemia, current recommendations on treatment for type 2 diabetes suggest several pharmacotherapies, including sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors and others. Among them, recent data emphasize the effectiveness at a lower risk for hypoglycemia of dipeptidyl peptidase-4 inhibitors compared to other drug groups. One particular drug from this group, sitagliptin offers sound effectiveness, safety and tolerability resulting in good glycemic control at a very low risk for hypoglycemia. This review explores available evidence on the optimal treatment for type 2 diabetes regarding glycemic control with minimal risk for hypoglycemia based on evidence from clinical trials and meta-analyses within the context of the current treatment recommendations by the Spanish Society of Diabetes.

Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypoglycemia; Hypoglycemic Agents; Pyrazines; Sitagliptin Phosphate; Triazoles

Inhibition of dipeptidyl peptidase-4 (DPP-4) is a novel oral treatment for type 2 diabetes. DPP-4 inhibition increases insulin secretion and reduces glucagon secretion by preventing the inactivation of glucagon-like peptide-1 (GLP-1), thereby lowering glucose levels. Several DPP-4 inhibitors are in clinical development; more studies exist for sitagliptin and vildagliptin. They improve metabolic control in type 2 diabetes in monotherapy and also in combination with metformin, sulphonylurea and thiazolidinediones. HbA(1c) is reduced by approximately 0.6-1.1% in studies up to 52 weeks. Similar, although more limited, results were obtained for saxagliptin. DPP-4 inhibitors are safe and tolerable with no increased risk of adverse events compared to placebo and have a low risk of hypoglycaemia. DPP-4 inhibitors are body weight-neutral. The DPP-4 inhibitors are recommended for use in the early stage of type 2 diabetes, in combination with metformin in subjects with inadequate glycaemic control. DPP-4 inhibition may also be used in combination with sulphonylurea and thiazolidinediones and potentially also in combination with insulin. The durability and long-term safety of DPP-4 inhibitors remain to be established.

Topics: Adamantane; Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Metformin; Nitriles; Pioglitazone; Pyrazines; Pyrrolidines; Sensitivity and Specificity; Sitagliptin Phosphate; Sulfonylurea Compounds; Thiazolidinediones; Triazoles; Vildagliptin

Maintaining an adequate metabolic control is still a challenge in many patients with type 2 diabetes. Among the many factors advocated to explain the failure to achieve recommended goals, clinical inertia is increasingly recognised as a primary cause of poor glycaemic control. The existence of a "metabolic memory" strongly supports the adoption of a more aggressive treat-to-target approach, instead of waiting for treatment failure. This approach may be particularly important in the initial phases of the disease, to slow the progressive decline of beta-cell function and improve overall outcomes. The fear of hypoglycaemia and weight gain associated with most of the available treatments are among the main causes of clinical inertia, and strongly affect the attitudes of providers and patients toward therapy intensification. The incretin-based therapies represent a new potential goal-oriented treatment approach. Two classes of incretin-based drugs have been developed: GLP-1 mimetics (exenatide and liraglutide) and DPP-IV inhibitors (sitagliptin and vildagliptin). Incretino-mimetics have a peculiar mechanism of action that is associated with lack of hypoglycaemia and weight loss or neutrality; these characteristics may facilitate therapy intensification and help to attain established goals. Furthermore, they can induce benefits in terms of post-prandial hyperglicemia control and beta-cell function preservation. An early use of this class of drugs may show a positive impact on the disease progression and a delay in the need of insulin injections.

Topics: Adamantane; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Exenatide; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incretins; Liraglutide; Nitriles; Peptides; Pyrazines; Pyrrolidines; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Triazoles; Venoms; Vildagliptin

Exenatide is an incretin mimetic, while sitagliptin and vildagliptin are incretin enhancers used as adjunctive therapy in patients with type 2 diabetes failing oral agents. Sitagliptin and vildagliptin can also be used as monotherapy in patients with type 2 diabetes uncontrolled by diet.. To provide a critical review of clinical trials of exenatide, sitagliptin and vildagliptin.. Review of Phase III clinical trials based on Medline search published up to April 2008.. The use of exenatide is associated with reduction in average hemoglobin A1c (HbA1c) levels of approximately 0.8% compared with baseline. The corresponding reduction with either sitagliptin or vildagliptin is 0.7%. The actions of incretin-based drugs predominantly target postprandial hyperglycemia. Treatment-related hypoglycemia is generally mild, and mainly occurs when used with sulfonylureas (SUs). Exenatide treatment leads to a mild weight loss of around 2 kg after 30 weeks, whereas sitagliptin and vildagliptin have generally neutral effect on weight. Sitagliptin and vildagliptin are well tolerated in trials lasting up to 52 weeks. Meanwhile, 5 - 10% of patients cannot tolerate exenatide due to adverse effects, mainly nausea and vomiting. The three drugs are limited by the lack of long-term safety and efficacy data, as well as by their high cost.. Exenatide, sitagliptin and vildagliptin are useful add-on therapy for type 2 diabetes that is suboptimally controlled on oral agents, particularly when there is concern about weight gain and hypoglycemia, or when postprandial hyperglycemia is the major cause of inadequate glycemic control. Sitagliptin and vildagliptin may be used as monotherapy in patients who cannot tolerate metformin or SU, and sitagliptin may be used as alternative to metformin in renal insufficiency.

Topics: Adamantane; Body Weight; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Therapy, Combination; Exenatide; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incretins; Insulin; Insulin Secretion; Nausea; Nitriles; Peptides; Pyrazines; Pyrrolidines; Randomized Controlled Trials as Topic; Receptors, Glucagon; Sitagliptin Phosphate; Triazoles; Venoms; Vildagliptin; Vomiting

Inhibition of dipeptidyl peptidase 4 (DPP-4) is a novel treatment for type-2 diabetes. DPP-4 inhibition prevents the inactivation of glucagon-like peptide 1 (GLP-1), which increases levels of active GLP-1. This increases insulin secretion and reduces glucagon secretion, thereby lowering glucose levels. Several DPP-4 inhibitors are in clinical development. Most experience so far has been with sitagliptin (Merck; approved by the FDA) and vildagliptin (Novartis; filed). These are orally active compounds with a long duration, allowing once-daily administration. Both sitagliptin and vildagliptin improve metabolic control in type-2 diabetes, both in monotherapy and in combination with metformin and thiazolidinediones. A reduction in HbA(1c) of approximately 1% is seen in studies of DPP-4 inhibition of up to 52 weeks' duration. DPP-4 inhibition is safe and well tolerated, the risk of hypoglycaemia is minimal, and DPP-4 inhibition is body-weight neutral. DPP-4 inhibition is suggested to be a first-line treatment of type-2 diabetes, particularly in its early stages in combination with metformin. However, the durability and long-term safety of DPP-4 inhibition remain to be established.

Topics: Adamantane; Animals; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glucagon; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Lipid Metabolism; Metformin; Nitriles; Pioglitazone; Protease Inhibitors; Pyrazines; Pyrrolidines; Sitagliptin Phosphate; Substrate Specificity; Thiazolidinediones; Triazoles; Vildagliptin

The effects of β-blocker therapy in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD) are unclear. We sought to evaluate associations between β-blocker use in T2D with ASCVD and cardiovascular (CV) outcomes.. In patients with T2D and ASCVD enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), an inverse probability of treatment-weighted Cox proportional hazards model was used to examine the association between baseline β-blocker therapy (at randomization) and the primary CV composite (defined as CV death, non-fatal myocardial infarction [MI], non-fatal stroke, or hospitalization for unstable angina), including in subgroups with prior MI and heart failure (HF); other outcomes evaluated included individual components of the primary composite, hospitalization for HF, and severe hypoglycemic events.. Of the 14,671 patients randomized, 9322 (64%) were on a β-blocker at baseline; these patients were more likely to have prior MI or HF. Over a median 3.0 (25th, 75th percentile: 2.2, 3.6) years, the risk of the primary CV composite was significantly higher with baseline β-blocker use versus no β-blocker use (4.5 vs. 3.4 events/100-patient years, adjusted hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05-1.29); no significant interaction was noted for patients with versus without prior MI or HF. Baseline β-blocker use was not associated with risks for severe hypoglycemic events (HR 1.14, 95% CI 0.88-1.48).. In this observational analysis of T2D and ASCVD, baseline β-blocker use was not associated with risks for severe hypoglycemia yet also was not associated with CV risk reduction over 3 years of follow-up, supporting a randomized examination of chronic β-blocker therapy in this patient population. (TECOS ClinicalTrials.gov number, NCT00790205).

Topics: Adrenergic beta-Antagonists; Aged; Angina, Unstable; Atherosclerosis; Atrial Fibrillation; Cardiovascular Diseases; Cause of Death; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Sitagliptin Phosphate; Stroke; Treatment Outcome

To compare the effects of continuing versus discontinuing sitagliptin when initiating and intensively titrating insulin glargine.. Eligible patients had inadequately controlled type 2 diabetes on metformin (≥1500 mg/d) in combination with a dipeptidyl peptidase-4 (DPP-4) inhibitor and/or a sulphonylurea. Those on metformin + sitagliptin were directly randomized; all others were switched to metformin + sitagliptin (discontinuing other DPP-4 inhibitors and sulphonylureas) and stabilized during a run-in period. At randomization, patients were allocated to continuing sitagliptin or discontinuing sitagliptin, with both groups initiating insulin glargine and titrating to a target fasting glucose of 4.0 to 5.6 mmol/L.. A total of 743 participants (mean glycated haemoglobin [HbA1c] 72.6 mmol/mol [8.8%], disease duration 10.8 years), were treated. After 30 weeks, the mean HbA1c and least squares (LS) mean change from baseline in HbA1c were 51.4 mmol/mol (6.85%) and -20.5 mmol/mol (-1.88%) in the sitagliptin group and 56.4 mmol/mol (7.31%) and -15.5 mmol/mol (-1.42%) in the placebo group; the difference in LS mean changes from baseline HbA1c was -5.0 mmol/mol (-0.46%; P < 0.001). The percentage of participants with HbA1c <53 mmol/mol (<7.0%) was higher (54% vs. 35%) and the mean daily insulin dose was lower (53 vs. 61 units) in the sitagliptin group. Despite lower HbA1c, event rates and incidences of hypoglycaemia were not higher in the sitagliptin group. Adverse events overall and changes from baseline in body weight were similar between the two treatment groups.. When initiating insulin glargine therapy, continuation of sitagliptin, compared with discontinuation, resulted in a clinically meaningful greater reduction in HbA1c without an increase in hypoglycaemia. ClinicalTrials.gov Identifier: NCT02738879.

Topics: Aged; Deprescriptions; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Least-Squares Analysis; Male; Metformin; Middle Aged; Sitagliptin Phosphate; Treatment Outcome

To compare the efficacy and safety of an intensification strategy of early triple combination therapy with dapagliflozin (DAPA) plus saxagliptin (SAXA) to a dual therapy strategy with sitagliptin (SITA) in patients with type 2 diabetes who are inadequately controlled with metformin (MET) monotherapy.. This multinational, active-controlled, parallel-group phase 3b trial randomized 461 patients, at least 18 years of age, with glycated haemoglobin (HbA1c) of 8%-10.5% (64-91 mmol/mol), to either DAPA plus SAXA or SITA, added to MET, for a 26-week double-blind treatment period and an extension of a 26-week blinded treatment period.. Mean (± SD) baseline HbA1c was 8.8% ± 0.9% (73.0 ± 9.3 mmol/mol). DAPA plus SAXA (n = 232) provided a greater reduction from baseline in HbA1c at Weeks 26 and 52 compared with SITA (n = 229) (adjusted mean ± SE change, Week 26: -1.41 ± 0.07% vs -1.07 ± 0.07% [-15.4 ± 0.8 mmol/mol vs 11.7 ± 0.8 mmol/mol]; P = 0.0008; Week 52: -1.29 ± 0.08% vs -0.81 ± 0.09% [14.1 ± 0.9 mmol/mol vs 8.9 ± 1.0 mmol/mol]). The between-group difference in adjusted mean (95% CI) change from baseline in HbA1c increased from -0.34 (-0.54, -0.14) at Week 26 to -0.48 (-0.71, -0.25) at Week 52. DAPA plus SAXA was generally well tolerated and the incidence of adverse events was similar in both treatment arms.. Early intensification to triple therapy with DAPA plus SAXA results in better, more durable glycaemic control than addition of SITA only (dual therapy) in patients with high HbA1c levels who are uncontrolled with MET monotherapy.

Topics: Adamantane; Aged; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptides; Double-Blind Method; Drug Therapy, Combination; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Sitagliptin Phosphate; Treatment Outcome

To compare the efficacy of sitagliptin versus pioglitazone as add-on drugs in patients with poorly controlled diabetes with metformin and sulfonylureas.. This is a randomized, open-label, parallel assignment clinical trial. Patients who had inadequate glycemic control [7% (53 mmol/mol) ≤ A1C < 11% (97 mmol/mol)] despite a minimum 6-month period of active treatment with metformin 2000 mg/day plus gliclazide 240 mg/day were enrolled in the study. HbA1C, fasting blood glucose (FBG), fasting plasma lipid parameters [total cholesterol (TC0, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)], systolic and diastolic blood pressure (SBP, DBP), weight, waist circumference, and body mass index were measured at baseline and after 17, 34, and 52 weeks of treatment. Generalized estimating equation analysis was done to compare treatment groups for continuous efficacy parameters.. No significant difference in HbA1C reduction was observed between the treatment groups during the study course. (P = 0.149, adjusted P = 0.434; coefficient - 0.11 ± 0.08). The FBG (P = 0.032; coefficient 7.44 ± 3.48), HDL-C (P = 0.001; coefficient - 2.69 ± 0.83), TG (P = 0.027; coefficient 12.63 ± 5.71) and SBP (P < 0.001; coefficient 5.43 ± 1.26) changes from baseline, and weight gain were greater in the pioglitazone group. The mean changes in LDL-C and TC from baseline to week 52 were greater in the sitagliptin group (P = 0.034; coefficient - 7.40 ± 3.50, P = 0.013; coefficient - 7.16 ± 2.88, respectively).. Sitagliptin and pioglitazone were equally effective in improvement of HbA1C. There were some differences in terms of lipid indices, weight gain, and SBP. The current study confirmed that both sitagliptin and pioglitazone are effective treatment options and the decision should be made for each individual based on the baseline characteristics.

Topics: Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Pioglitazone; Prognosis; Sitagliptin Phosphate; Sulfonylurea Compounds

To investigate the effects of acarbose, sitagliptin, verapamil, liraglutide and pasireotide on post-bariatric hypoglycaemia (PBH) after Roux-en-Y gastric bypass.. In a randomized crossover study, 11 women who had undergone Roux-en-Y gastric bypass and had documented hypoglycaemia were each evaluated during a baseline period without treatment and during five treatment periods with the following interventions: acarbose 50 mg for 1 week, sitagliptin 100 mg for 1 week, verapamil 120 mg for 1 week, liraglutide 1.2 mg for 3 weeks and pasireotide 300 μg as a single dose. Treatment effects were evaluated by a mixed-meal tolerance test (MMTT) and, for all treatment periods except pasireotide, by 6 days of continuous glucose monitoring (CGM).. Treatment with acarbose and treatment with pasireotide both significantly lifted nadir glucose levels (mean ± SEM 3.9 ± 0.2 and 7.9 ± 0.4 vs 3.4 ± 0.2; P < .03) and reduced time in hypoglycaemia during the MMTTs. Acarbose reduced peak glucose levels and time in hyperglycaemia, whereas pasireotide greatly increased both variables. Acarbose and pasireotide reduced insulin and C-peptide levels, and pasireotide also diminished glucagon-like peptide-1 levels. Sitagliptin lowered nadir glucose values, while verapamil and liraglutide had no effect on hypoglycaemia. During the CGM periods, the treatments had no impact on hypoglycaemia, whereas acarbose and liraglutide reduced hyperglycaemia and glycaemic variability.. In an experimental setting, treatment with acarbose and pasireotide reduced PBH. Acarbose appears to have an overall glucose-stabilizing effect, whereas pasireotide leads to increased and sustained hyperglycaemia.

Topics: Acarbose; Adult; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Male; Middle Aged; Obesity, Morbid; Postoperative Complications; Postprandial Period; Sitagliptin Phosphate; Somatostatin; Treatment Outcome; Verapamil

To assess the safety and efficacy of monotherapy with once-weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D).. In this phase IIIa randomized, open-label, parallel-group, active-controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the run-in period) received once-weekly s.c. semaglutide (0.5 or 1.0 mg) or once-daily oral sitagliptin 100 mg. The primary endpoint was number of treatment-emergent adverse events (TEAEs) after 30 weeks.. Overall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants in both the semaglutide 0.5 mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0 mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0 mg groups were attributable to adverse events (AEs). More TEAEs were reported in semaglutide- vs sitagliptin-treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5 mg, semaglutide 1.0 mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0 mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin -1.13%, 95% confidence interval [CI] -1.32; -0.94, and -1.44%, 95% CI -1.63; -1.24; both P < .0001). Body weight (baseline 69.3 kg) was reduced by 2.2 and 3.9 kg with semaglutide 0.5 and 1.0 mg, respectively (ETD -2.22 kg, 95% CI -3.02; -1.42 and -3.88 kg, 95% CI -4.70; -3.07; both P < .0001).. In Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon-like peptide-1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin.

Topics: Administration, Oral; Constipation; Diabetes Mellitus, Type 2; Diarrhea; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Incretins; Injections, Subcutaneous; Japan; Nausea; Patient Dropouts; Severity of Illness Index; Sitagliptin Phosphate; Weight Loss

To evaluate the efficacy and safety of ertugliflozin and sitagliptin co-administration vs the individual agents in patients with type 2 diabetes who are inadequately controlled with metformin.. In this study (Clinicaltrials.gov NCT02099110), patients with glycated haemoglobin (HbA1c) ≥7.5% and ≤11.0% (≥58 and ≤97 mmol/mol) with metformin ≥1500 mg/d (n = 1233) were randomized to ertugliflozin 5 (E5) or 15 (E15) mg/d, sitagliptin 100 mg/d (S100) or to co-administration of E5/S100 or E15/S100. The primary endpoint was change from baseline in HbA1c at Week 26.. At Week 26, least squares mean HbA1c reductions from baseline were greater with E5/S100 (-1.5%) and E15/S100 (-1.5%) than with individual agents (-1.0%, -1.1% and -1.1% for E5, E15 and S100, respectively; P < .001 for all comparisons). HbA1c <7.0% (<53 mmol/mol) was achieved by 26.4%, 31.9%, 32.8%, 52.3% and 49.2% of patients in the E5, E15, S100, E5/S100 and E15/S100 groups, respectively. Fasting plasma glucose reductions were significantly greater with E5/S100 and E15/S100 compared with individual agents. Body weight and systolic blood pressure (SBP) significantly decreased with E5/S100 and E15/S100 vs S100 alone. Glycaemic control, body weight and SBP effects of ertugliflozin were maintained to Week 52. Genital mycotic infections were more common among ertugliflozin-treated patients compared with those treated with S100. Incidences of symptomatic hypoglycaemia and adverse events related to hypovolaemia or urinary tract infection were similar among groups.. In patients with uncontrolled type 2 diabetes while using metformin, co-administration of ertugliflozin and sitagliptin provided more effective glycaemic control through 52 weeks compared with the individual agents.

Topics: Aged; Body Mass Index; Bridged Bicyclo Compounds, Heterocyclic; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Overweight; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors

G protein-coupled receptor 119 (GPR119) is a promising target for the treatment of type 2 diabetes mellitus (T2DM), as both insulin and glucagon-like peptide-1 secretion can be promoted with a single drug. We compared the efficacy and safety of the GPR119 agonist DS-8500a with placebo and sitagliptin 50 mg in Japanese patients with T2DM.. DS-8500a demonstrated dose-dependent HbA1c lowering compared with placebo at week 12: change from baseline - 0.23% (p = 0.0173), - 0.37% (p = 0.0001), and - 0.44% (p < 0.0001) in the 25-mg, 50-mg, and 75-mg groups, respectively. At 50- and 75-mg doses, DS-8500a significantly lowered FPG, glucose AUC. DS-8500a was well tolerated and demonstrated significant glucose-lowering effects and favorable changes in lipid profiles up to 12 weeks in Japanese patients with T2DM.. Daiichi Sankyo Co. Ltd.

Topics: Adult; Aged; Benzamides; Cyclopropanes; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Japan; Male; Middle Aged; Oxadiazoles; Receptors, G-Protein-Coupled; Sitagliptin Phosphate; Treatment Outcome

Maintainance of glucagon response to hypoglycaemia is important as a safeguard against hypoglycaemia during glucose-lowering therapy in type 2 diabetes. During recent years, DPP-4 (dipeptidyl peptidase-4) inhibition has become more commonly used in elderly patients. However, whether DPP-4 inhibition affects the glucagon response to hypoglycaemia in the elderly is not known and was the aim of this study.. In a single-centre, double-blind, randomized, placebo-controlled crossover study, 28 subjects with metformin-treated type 2 diabetes (17 male, 11 female; mean age, 74 years [range 65-86]; mean HbA1c, 51.5 mmol/mol [6.9%]) received sitagliptin (100 mg once daily) as add-on therapy or placebo for 4 weeks with a 4-week washout period in between. After each treatment period, the subjects underwent a standard breakfast test, followed by a 2-step hyperinsulinaemic hypoglycaemic clamp (target 3.5 and 3.0 mmol/L), followed by lunch.. Glucagon levels after breakfast and lunch, and the glucagon response at 3.5 mmol/L, were lower after sitagliptin than after placebo. However, the glucagon response to hypoglycaemia at 3.1 mmol/L did not differ significantly between the two. Similarly, the noradrenaline, adrenaline and cortisol responses were lower with sitagliptin than with placebo at 3.5 mmol/L, but not at 3.1 mmol/L glucose. Responses in pancreatic polypeptide did not differ between the two.. Elderly subjects with metformin-treated type 2 diabetes have lower glucagon levels at 3.5 mmol/L glucose, but maintain the glucagon response to hypoglycaemia at 3.1 mmol/L during DPP-4 inhibition, which safeguards against hypoglycaemia and may contribute to decreasing the risk of hypoglycaemia by DPP-4 inhibition in this age group.

Topics: Aged; Aged, 80 and over; Aging; Cross-Over Studies; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Therapy, Combination; Female; Glucagon; Glucagon-Secreting Cells; Glucose Clamp Technique; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Male; Meals; Metformin; Risk; Sitagliptin Phosphate; Sweden

The efficacy and safety of semaglutide vs comparators in non-elderly (<65 years) and elderly (≥65 years) patients with type 2 diabetes (T2D) across the SUSTAIN 1-5 trials were evaluated. Patients were randomized to once-weekly subcutaneous semaglutide (0.5 or 1.0 mg) vs placebo, sitagliptin, exenatide or insulin. The primary objective was change in HbA1c and secondary objectives were changes in body weight and safety. Mean HbA1c decreased from baseline by 1.2%-1.5% and 1.5%-1.9% vs 0%-0.9% (non-elderly, n = 3045) and by 1.3%-1.5% and 1.2%-1.8% vs 0.2%-1.0% (elderly, n = 854) with semaglutide 0.5 and 1.0 mg vs comparators. Similar reductions from baseline in mean body weight with semaglutide occurred in both age groups. Similar proportions of patients experienced adverse events; premature treatment discontinuations were higher in elderly vs non-elderly patients. No increased risk of severe or blood glucose-confirmed hypoglycaemia was seen with semaglutide vs comparators between age groups. Semaglutide had a comparable efficacy and safety profile in non-elderly and elderly patients across the SUSTAIN 1-5 trials, making it an effective treatment option for elderly patients with T2D.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Female; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Sitagliptin Phosphate; Treatment Outcome

To evaluate the pharmacodynamics of lixisenatide once daily vs sitagliptin once daily in Japanese patients with type 2 diabetes receiving insulin glargine U100.. This multicentre, open-label, phase IV study (NEXTAGE Study; ClinicalTrials.gov number, NCT02200991) randomly assigned 136 patients to either lixisenatide once daily via subcutaneous injection (10 µg initially increased weekly by 5 up to 20 µg) or once-daily oral sitagliptin 50 mg. The primary endpoint was the change in postprandial glucose (PPG) exposure 4 hours after a standardized breakfast (PPG area under the plasma glucose concentration-time curve [AUC. Lixisenatide reduced PPG significantly more than sitagliptin, when these agents were added to basal insulin glargine U100, and was well tolerated.

Topics: Administration, Oral; Aged; Biomarkers; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Female; Follow-Up Studies; Gastric Emptying; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Japan; Male; Middle Aged; Peptides; Postprandial Period; Sitagliptin Phosphate

To evaluate the safety and efficacy of sitagliptin when added to the treatment of patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on acarbose monotherapy.. This was a multicenter, randomized, placebo-controlled, double-blind clinical trial. Patients (N = 381) with T2DM and inadequate glycemic control (glycated hemoglobin [HbA1c] ≥ 7.0% and ≤10.0%) on acarbose monotherapy (at least 50 mg three times daily) were randomized in a 1:1 ratio to receive the addition of sitagliptin 100 mg or matching placebo once daily for 24 weeks.. Changes from baseline in HbA1c and fasting plasma glucose (FPG) at Week 24.. The mean baseline HbA1c in randomized patients was 8.1%. At Week 24, the placebo-controlled, least squares mean changes from baseline (95% confidence interval) in HbA1c and FPG in the sitagliptin group were -0.62% and -0.8 mmol/L (p < .001), respectively. At Week 24, 37.8% of patients in the sitagliptin group were at HbA1c goal of <7% compared with 17.2% in the placebo group (p < .001). Sitagliptin was generally well tolerated, and there were no significant between-group differences in prespecified safety parameters (symptomatic hypoglycemia, diarrhea, abdominal pain, nausea, vomiting). A higher incidence of serious adverse events was observed in the sitagliptin group (5.2%) relative to placebo (0.5%); all but one, in the sitagliptin group, were not considered related to drug.. Sitagliptin was generally well tolerated and provided statistically superior and clinically meaningful improvements in glycemic control after 24 weeks of treatment compared to placebo when added to treatment of patients with inadequate glycemic control on acarbose monotherapy. Clinicaltrials.gov: NCT01177384.

Topics: Acarbose; Adult; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Monitoring; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Sitagliptin Phosphate; Treatment Outcome

Clinical and safety event summaries are presented for older versus younger participants and for the treatment groups within the older cohort.. Of 14,351 participants with age recorded, 2,004 (14%) were ≥75 years old (mean age 78.3 years [SD 3.1]), with 68% men and type 2 diabetes duration median 12.0 years (IQR 7, 21). During 2.9 years median follow-up, older participants had higher rates of the primary outcome (6.46 vs. 3.67 events per 100 person-years; hazard ratio 1.72 [95% CI 1.52-1.94]), death (2.52 [2.20-2.89]), severe hypoglycemia (1.53 [1.15-2.03]), and fractures (1.84 [1.44-2.35]). In the older cohort, sitagliptin did not significantly impact the primary composite (1.10 [0.89-1.36]), death (1.05 [0.83-1.32]), heart failure hospitalization (0.99 [0.65-1.49]), severe hypoglycemia (1.03 [0.62-1.71]), rates of acute pancreatitis and pancreatic cancer, or serious adverse events.. Among older patients with well-controlled type 2 diabetes and cardiovascular disease, sitagliptin had neutral effects on cardiovascular risk and raised no significant safety concerns.

Topics: Aged; Aged, 80 and over; Body Mass Index; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Risk Factors; Sitagliptin Phosphate; Stroke; Treatment Outcome

This trial consisted of a 24-week multicentre, randomized, double-blind, double-dummy, active-controlled study and a 52-week open label extension study to assess the efficacy and safety of evogliptin, a novel dipeptidyl peptidase-4 inhibitor, compared to sitagliptin in patients with type 2 diabetes who have inadequate glycaemic control with metformin alone.. Adult patients with type 2 diabetes mellitus (N = 222) with HbA1c 6.5% to 11% who were receiving stable doses of metformin (≥1000 mg/d) were randomized 1:1 to add-on evogliptin 5 mg (N = 112) or sitagliptin 100 mg (N = 110) once daily for 24 weeks. The primary efficacy analysis consisted of a comparison of the change from baseline HbA1c at week 24. Non-inferiority was concluded if the upper limit of the 2-sided 95% confidence interval for the HbA1c difference between treatments was <0.35%.. Mean changes in HbA1c following addition of evogliptin or sitagliptin were -0.59% and -0.65%, respectively. The between-group difference was 0.06% (2-sided 95% confidence interval, -0.10 to 0.22), demonstrating non-inferiority. After the 52-week treatment, evogliptin caused a persistently decreased level of HbA1c (-0.44% ± 0.65%, P  < .0001). In general, both treatments were well tolerated, with incidences and types of adverse events comparable between the two groups. Hypoglycaemic events, mostly mild, were reported in 0.9% of patients treated with evogliptin and in 2.8% of patients treated with sitagliptin for 24 weeks.. Evogliptin 5 mg added to metformin therapy effectively improved glycaemic control and was non-inferior to sitagliptin and well tolerated in patients with type 2 diabetes mellitus that was inadequately controlled by metformin alone.

Topics: Aged; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Male; Metformin; Middle Aged; Piperazines; Republic of Korea; Sitagliptin Phosphate

To evaluate the efficacy and safety of fasiglifam, an orally active G-protein-coupled receptor 40 agonist, in combination with the dipeptidyl peptidase-4 inhibitor sitagliptin, in patients with type 2 diabetes inadequately controlled with diet/exercise (± metformin).. In this randomized, double-blind, phase II study, 368 patients received once-daily placebo, sitagliptin 100 mg, fasiglifam 25 or 50 mg, or the combination of sitagliptin 100 mg plus fasiglifam 25 or 50 mg. The primary endpoint was change from baseline glycated haemoglobin (HbA1c) at 12 weeks; a key secondary endpoint was change in fasting plasma glucose (FPG).. The fasiglifam 25 and 50 mg combination regimens produced significantly greater HbA1c reductions than sitagliptin (treatment differences of -0.45% and -0.61%; P < .01, respectively) or respective doses of fasiglifam monotherapy (-0.43% and -0.48%; P < .01) and significantly greater FPG reductions than sitagliptin (-1.1 mmol/L for both combination regimens; P < .01). Improved glycaemic control occurred by week 1 for FPG and week 4 for HbA1c in all groups. Hypoglycaemia rates were low (≤3.3%) and similar across treatments. Liver enzymes >3 × upper limit of normal occurred in four patients (fasiglifam 25 mg, n = 1; fasiglifam 50 mg, n = 2; 1 fasiglifam/sitagliptin 50/100 mg, n = 1).. Combination of fasiglifam and sitagliptin provided significant additional effects on glycaemic control, with hypoglycaemia rates similar to placebo with or without metformin. This study provides supportive clinical evidence for the complementary mechanism of actions of this GPR40 agonist and DPP-4 inhibitor.

Topics: Benzofurans; Combined Modality Therapy; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Female; Hemoglobins, Abnormal; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Incretins; Male; Metformin; Middle Aged; Receptors, G-Protein-Coupled; Sitagliptin Phosphate; Sulfones; United States

The aim of this study was to evaluate the efficacy and safety of sitagliptin administered to elderly patients with type 2 diabetes mellitus (T2DM) for 1 year as compared with glimepiride. Patients aged ≥60 years with T2DM and inadequately controlled blood glucose were randomly assigned to sitagliptin 50 mg once daily or glimepiride 0.5 mg once daily for 52 weeks. The primary efficacy endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 52. Secondary efficacy endpoints included self-monitored blood glucose and weight. Safety endpoints were adverse events including hypoglycaemia. Administration of sitagliptin or glimepiride to elderly patients with T2DM resulted in a significant decrease in HbA1c change from baseline. At 52 weeks, the least squares mean difference between the treatments was 0.11% (95% confidence interval [CI] -0.02 to 0.24; P = .087) (1.2 mmol/mol [-0.2 to 2.6]). The upper limit of the CI was below the predefined non-inferiority margin (0.3% [3.3 mmol/mol]), demonstrating non-inferiority of sitagliptin to glimepiride for the primary endpoint. Sitagliptin resulted in a significantly lower incidence rate of non-serious hypoglycaemia than glimepiride during the 52 weeks (4.7% vs 16.1%; P = .002); thus, sitagliptin is a useful therapeutic option for elderly patients with T2DM.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Aging; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Equivalence Trials as Topic; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Incretins; Japan; Middle Aged; Reproducibility of Results; Severity of Illness Index; Sitagliptin Phosphate; Sulfonylurea Compounds; Weight Loss

In this clinical trial, we investigated the blood glucose (BG)-lowering effects of 30, 60 and 90 mg dextromethorphan (DXM) as well as 100 mg sitagliptin alone versus combinations of DXM and sitagliptin during an oral glucose tolerance test (OGTT) in 20 men with T2DM. The combination of 60 mg DXM plus 100 mg sitagliptin was observed to have the strongest effect in the OGTT. It lowered maximum BG concentrations and increased the baseline-adjusted area under the curve for serum insulin concentrations in the first 30 min of the OGTT (mean ± standard deviation 240 ± 47 mg/dl and 8.1 ± 6.1 mU/l/h, respectively) to a significantly larger extent than did 100 mg sitagliptin alone (254 ± 50 mg/dl and 5.8 ± 2.5 mU/l/h, respectively; p < 0.05) and placebo (272 ± 49 mg/dl and 3.9 ± 3.0 mU/l/h, respectively; p < 0.001). All study drugs were well tolerated, alone and in combination, without serious adverse events or hypoglycaemia. Long-term clinical trials are now warranted to investigate the potential of the combination of 30 or 60 mg DXM and dipeptidyl peptidase-4 inhibitors in the treatment of individuals with T2DM, in particular as preclinical studies have identified the β-cell protective properties of DXM.

Topics: Aged; Blood Glucose; Cross-Over Studies; Dextromethorphan; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Glucose Tolerance Test; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Sitagliptin Phosphate

To compare the efficacy and safety of liraglutide versus sitagliptin as add-on to metformin after 26 weeks of treatment in Chinese patients with type 2 diabetes mellitus (T2DM).. This 26-week open-label, active comparator trial (NCT02008682) randomized patients (aged 18-80 years) with T2DM inadequately controlled with metformin [glycated haemoglobin (HbA1c) 7.0-10.0% (53-86 mmol/mol)] 1 : 1 to once-daily subcutaneously administered liraglutide 1.8 mg (n = 184) or once-daily oral sitagliptin 100 mg (n = 184), both as add-on to metformin. The primary endpoint was change in HbA1c from baseline to week 26.. Liraglutide was superior to sitagliptin in reducing HbA1c from baseline [8.1% (65 mmol/mol)] to 26 weeks, as evidenced by estimated mean HbA1c change of -1.65% (-18.07 mmol/mol) versus -0.98% (-10.72 mmol/mol), respectively [estimated treatment difference for liraglutide vs sitagliptin of -0.67% (95% CI -0.86, -0.48) or -7.35 mmol/mol (95% CI -9.43; -5.26); p < 0.0001]. More patients receiving liraglutide (76.5%) than sitagliptin (52.6%) achieved the HbA1c target of <7.0% (53 mmol/mol) at week 26 [odds ratio 3.65 (95% CI 2.18, 6.12); p < 0.0001]. Reductions in fasting plasma glucose, 7-point self-measured plasma glucose and body weight were greater with liraglutide than with sitagliptin (p < 0.0001 for all). More patients experienced nausea (14.8% vs 0.5%), diarrhoea (8.2% vs 2.2%) and decreased appetite (10.9% vs 0.5%) with liraglutide than sitagliptin. Two hypoglycaemic episodes were confirmed for liraglutide and one for sitagliptin; none were severe or nocturnal.. Liraglutide provided better glycaemic control and greater body weight reduction than sitagliptin when administered as add-on to metformin. More patients had nausea, diarrhoea and decreased appetite with liraglutide versus sitagliptin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anorexia; Asian People; Blood Glucose; Body Weight; China; Diabetes Mellitus, Type 2; Diarrhea; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Male; Metformin; Middle Aged; Nausea; Sitagliptin Phosphate; Treatment Outcome; Young Adult

To evaluate the efficacy and safety of titrated canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin and sitagliptin.. In this randomized, double-blind study, patients with T2DM (N = 218) on metformin ≥1500 mg/day and sitagliptin 100 mg received canagliflozin 100 mg or placebo. After 6 weeks, the canagliflozin dose was increased from 100 to 300 mg (or from placebo to matching placebo) if all of the following criteria were met: baseline estimated glomerular filtration rate ≥70 ml/min/1.73 m(2) ; fasting self-monitored blood glucose ≥5.6 mmol/l (≥100 mg/dl); and no volume depletion-related adverse events (AEs) within 2 weeks before dose increase. Endpoints included change in glycated haemoglobin (HbA1c) at week 26 (primary); proportion of patients achieving HbA1c <7.0%; and changes in fasting plasma glucose (FPG), body weight and systolic blood pressure (SBP). Safety was assessed using AE reports.. Overall, 85.4% of patients were titrated to canagliflozin 300 mg or matching placebo (mean ± standard deviation time to titration 6.2 ± 0.8 weeks). At week 26, canagliflozin (pooled 100 and 300 mg) demonstrated superiority in HbA1c reduction versus placebo (-0.91% vs. -0.01%; p < 0.001). Canagliflozin provided significant reductions in FPG, body weight and SBP compared with placebo (p < 0.001). The overall AE incidence was 39.8 and 44.4% for canagliflozin and placebo, respectively. Canagliflozin was associated with an increased incidence of genital mycotic infections.. Titrated canagliflozin significantly improved HbA1c, FPG, body weight and SBP, and was generally well tolerated over 26 weeks in patients with T2DM as add-on to metformin and sitagliptin.

Topics: Aged; Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Hypovolemia; Male; Metformin; Middle Aged; Mycoses; Reproductive Tract Infections; Sitagliptin Phosphate; Treatment Failure; Treatment Outcome; Urinary Tract Infections

To confirm superiority on glycaemic control by switching from sitagliptin to liraglutide 1.8 mg/d versus continued sitagliptin.. A randomized, multicentre, double-blind, double-dummy, active-controlled trial across 86 office- or hospital-based sites in North America, Europe and Asia. Subjects with type 2 diabetes who had inadequate glycaemic control (glycated haemoglobin [HbA1c] 7.5-9.5% on sitagliptin (100 mg/d) and metformin (≥1500 mg daily) for ≥90 days were randomized to either switch to liraglutide (n = 203) or continue sitagliptin (n = 204), both with metformin. The primary endpoint was change in HbA1c from baseline to week 26. Change in body weight was a confirmatory secondary endpoint.. Greater reduction in mean HbA1c was achieved with liraglutide than with continued sitagliptin [-1.14% vs. -0.54%; estimated mean treatment difference (ETD): -0.61% (95% CI -0.82 to -0.40; p < 0.0001)], confirming superiority of switching to liraglutide. Body weight was reduced more with liraglutide [-3.31 kg vs. -1.64 kg; ETD: -1.67 kg (95% CI -2.34 to -0.99; p < 0.0001)]. Nausea was more common with liraglutide [44 subjects (21.8%)] than with continued sitagliptin [16 (7.8%)]. Three subjects (1.5%) taking sitagliptin reported a confirmed hypoglycaemic episode.. Subjects insufficiently controlled with sitagliptin who switch to liraglutide can obtain clinically relevant reductions in glycaemia and body weight, without compromising safety. A switch from sitagliptin to liraglutide provides an option for improved management of type 2 diabetes while still allowing patients to remain on dual therapy.

Topics: Adult; Aged; Aged, 80 and over; Asia; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Substitution; Drug Therapy, Combination; Europe; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Male; Metformin; Middle Aged; Nausea; North America; Sitagliptin Phosphate; Treatment Outcome

To assess whether the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin affects glucagon and other counter-regulatory hormone responses to hypoglycaemia in patients with type 1 diabetes.. We conducted a single-centre, randomized, double-blind, placebo-controlled, three-period crossover study. We studied 16 male patients with type 1 diabetes aged 18-52 years, with a diabetes duration of 5-20 years and intact hypoglycaemia awareness. Participants received sitagliptin (100 mg/day) or placebo for 6 weeks and attended the hospital for three acute hypoglycaemia studies (at baseline, after sitagliptin treatment and after placebo). The primary outcome was differences between the three hypoglycaemia study days with respect to plasma glucagon responses from the initialization phase of the hypoglycaemia intervention to 40 min after onset of the autonomic reaction.. Sitagliptin treatment significantly increased active levels of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. No significant differences were observed for glucagon or adrenergic counter-regulatory responses during the three hypoglycaemia studies. Growth hormone concentration at 40 min after occurrence of autonomic reaction was significantly lower after sitagliptin treatment [median (IQR) 23 (0.2-211.0) mEq/l] compared with placebo [median (IQR) 90 (8.8-180) mEq/l; p = 0.008].. Sitagliptin does not affect glucagon or adrenergic counter-regulatory responses in patients with type 1 diabetes, but attenuates the growth hormone response during late hypoglycaemia.

Topics: Adolescent; Adult; Cross-Over Studies; Diabetes Mellitus, Type 1; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Growth Hormone; Humans; Hypoglycemia; Incretins; Male; Middle Aged; Sitagliptin Phosphate; Young Adult

To investigate the efficacy and safety of ertugliflozin, in a phase II dose-ranging study, in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin.. A total of 328 patients [mean T2DM duration, 6.3 years; mean glycated haemoglobin (HbA1c), 8.1%] were randomized to once-daily ertugliflozin (1, 5, 10, 25 mg), sitagliptin (100 mg) or placebo, for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in HbA1c concentration and the secondary efficacy endpoints were changes from baseline to week 12 in body weight, fasting plasma glucose (FPG) and systolic/diastolic blood pressure (SBP/DBP). Safety and tolerability were also monitored.. Ertugliflozin (1-25 mg/day) produced significant reductions in HbA1c concentration [placebo-corrected least-squares mean (LSM) -0.45% (1 mg) to -0.72% (25 mg); p ≤ 0.002, similar to sitagliptin (-0.76%; p = 0.0001)], FPG (LSM -1.17 to -1.90 mmol/l; p < 0.0001) and body weight (-1.15 to -2.15%; p < 0.0001). The LSM SBP decreased by -3.4 to -4.0 mmHg from baseline with ertugliflozin 5-25 mg/day. No reductions in body weight or blood pressure were observed with sitagliptin. After randomization, 2.7% of patients (9/328) withdrew because of adverse events (AEs); the frequency of AEs was evenly distributed across groups. No dose-related increase in AE frequency occurred with ertugliflozin. Hypoglycaemia was reported in 5 (1.5%) randomized participants (all in the ertugliflozin group). The frequency of urinary tract infection was 3.2% for ertugliflozin (pooled across groups), 1.8% for sitagliptin, 7.4% for placebo, and the frequency of genital fungal infections was 3.7% for ertugliflozin (pooled) versus 1.9% for placebo.. Ertugliflozin (1-25 mg/day) improved glycaemic control, body weight and blood pressure in patients with T2DM suboptimally controlled on metformin, and was well tolerated.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Weight; Bridged Bicyclo Compounds, Heterocyclic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Genital Diseases, Female; Genital Diseases, Male; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Mycoses; Sitagliptin Phosphate; Sodium-Glucose Transport Proteins; Urinary Tract Infections

To assess the efficacy and safety of a range of doses of a systemic, partial, glucokinase activator, PF-04937319, as add-on therapy to metformin, in patients with type 2 diabetes mellitus (T2DM).. Patients were randomized to once-daily PF-04937319 doses of 10, 50, 100 mg, or matching placebo (Study B1621002); or PF-04937319 doses of 3, 20, 50, 100 mg, or matching placebo (Study B1621007). Titrated glimepiride (Study B1621002) or sitagliptin (Study B1621007) were included in a double-dummy manner. The primary measure was change from baseline in glycated haemoglobin (HbA1c) at week 12. Key secondary measures included other glycaemic variables and safety and tolerability.. In the 639 patients randomized, the minimally efficacious PF-04937319 dose was identified as 50 mg once daily. At the highest PF-04937319 dose tested (100 mg), on average, a clinically significant reduction in HbA1c [-4.94 or -5.11 mmol/mol (-0.45 or -0.47%), placebo-adjusted], which was similar to that achieved with sitagliptin [-4.69 mmol/mol (-0.43%)] but lower than that achieved with titrated glimepiride [-9.07 mmol/mol (-0.83%)], was observed. At this dose, the effect on fasting plasma glucose was not consistent between the two studies (Study B1621002 vs Study B1621007: placebo-adjusted mean change of -0.83 vs +0.50 mmol/l). PF-04937319 was well tolerated at doses up to 100 mg. Hypoglycaemia was reported in 2.5% of patients (on placebo), 5.1% of patients (on PF-04937319 100 mg), 1.8% of patients (on sitagliptin) and 34.4% of patients (on titrated glimepiride).. In patients on metformin monotherapy, the addition of a 100-mg dose of PF-04937319 improved glycaemic control and was well tolerated.

Topics: Aged; Benzofurans; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Fasting; Female; Glucokinase; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Pyrimidines; Sitagliptin Phosphate; Sulfonylurea Compounds

The aim of this study was to evaluate the efficacy and tolerability of sitagliptin compared with glimepiride in elderly patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control with diet and exercise alone.. This was a randomized, parallel-group, multinational, non-inferiority clinical trial with an active-controlled, double-blind treatment period in which patients ≥ 65 and ≤ 85 years of age with T2DM were screened at 85 sites. Patients were randomized to once-daily sitagliptin (100 or 50 mg, depending on renal function) or glimepiride (in titrated doses) for 30 weeks. The main outcome measures were change from baseline in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight; and the incidence of symptomatic hypoglycemia.. The mean baseline HbA1c was 7.8% in both the sitagliptin group (n = 197) and the glimepiride group (n = 191). After 30 weeks, the least squares (LS) mean change in HbA1c baseline was -0.32% with sitagliptin and -0.51 % with glimepiride, for a between-group difference (95% CI) of 0.19% (0.03-0.34). This result met the pre-specified criterion for declaring non-inferiority, which required that the upper 95% confidence limit lie below 0.4%. The LS mean change in FPG from baseline was -14.5 mg/dL with sitagliptin and -21.2 mg/dL with glimepiride, for a between-group difference (95% CI) of 6.7 mg/dL (0.7-12.7). The percentages of patients with adverse events of symptomatic hypoglycemia were 0.8% in the sitagliptin group and 4.7% in the glimepiride group (between-treatment difference = -3.9%, p = 0.009). The LS mean change in body weight from baseline was 0.4 kg with sitagliptin and 1.1 kg with glimepiride, for a between-group difference of -0.7 kg (p = 0.011).. In elderly patients with T2DM and inadequate glycemic control with diet and exercise alone, sitagliptin provided non-inferior glycemic control after 30 weeks of treatment compared with glimepiride. Compared with glimepiride, sitagliptin had a lower risk of hypoglycemia. Sitagliptin was weight-neutral; while the between-group difference in change from baseline in body weight was statistically significant, the modest difference may not be clinically meaningful.. ClinicalTrials.gov NCT01189890.

Topics: Age Factors; Aged; Aged, 80 and over; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diet; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Sitagliptin Phosphate; Sulfonylurea Compounds; Treatment Outcome

To evaluate the efficacy and safety of initial combination therapy of sitagliptin 100 mg/day coadministered with all marketed doses of pioglitazone in patients with type 2 diabetes.. Patients with A1c ≥7.5 and ≤11.0% were randomized among seven arms that received, once daily, 100 mg sitagliptin alone; 15, 30 or 45 mg pioglitazone alone, or 100 mg sitagliptin plus 15, 30 or 45 mg pioglitazone for 54 weeks. The primary endpoint was change from baseline in A1c at week 24. Protocol-specified analyses compared combination therapies with monotherapies at respective dose-strengths and combination of sitagliptin plus pioglitazone 30 mg with pioglitazone 45 mg monotherapy. Post-hoc analyses compared sitagliptin plus pioglitazone 15 mg with pioglitazone monotherapy at the two higher doses.. Initial combination therapy with sitagliptin and pioglitazone provided significantly greater reductions in A1c (0.4-0.7% differences) and other glycaemic endpoints than either monotherapy at the same doses. Combining sitagliptin with low-dose pioglitazone generally produced greater glycaemic improvements than higher doses of pioglitazone monotherapy (0.3-0.4% differences in A1c). Combination therapy was generally well tolerated; adverse events (AEs) of hypoglycaemia were reported with similar incidence (7.8-11.1%) in all treatment groups over the 54 weeks of study; oedema was reported in 0.5% of patients in the sitagliptin monotherapy group and 2.7-5.3% among pioglitazone-treated groups. Significant weight gain was observed in all combination-treated groups compared with the sitagliptin monotherapy group.. Initial combination therapy with sitagliptin and pioglitazone provided better glycaemic control than either monotherapy and was generally well tolerated.

Topics: Adolescent; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Middle Aged; Pioglitazone; Pyrazines; Sitagliptin Phosphate; Thiazolidinediones; Treatment Outcome; Triazoles

Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for treatment of type 2 diabetes mellitus (T2DM). The long-term efficacy and safety of canagliflozin monotherapy were evaluated over 52 weeks in patients with T2DM inadequately controlled with diet and exercise.. This randomized, double-blind, Phase 3 study included a placebo-controlled, 26-week core period (canagliflozin 100 or 300 mg vs placebo) and an active-controlled, 26-week extension (blinded switch of placebo-treated patients to sitagliptin 100 mg [placebo/sitagliptin]).. ClinicalTrials.gov, NCT01081834.. Efficacy endpoints assessed at 52 weeks included changes in hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and systolic blood pressure (BP); and percentage changes in body weight and fasting plasma lipids. Adverse events (AEs) were recorded throughout the study. Efficacy data are reported for canagliflozin 100 and 300 mg (placebo/sitagliptin group was used to maintain the double-blind and to serve as a control group for safety purposes; not as an efficacy comparator); safety data are reported for canagliflozin 100 and 300 mg and placebo/sitagliptin.. Efficacy analyses included 451 patients who were randomized and dosed, entered the extension, and did not receive rescue therapy during the core period. Safety analyses included 584 patients who were randomized and dosed. At Week 52, canagliflozin 100 and 300 mg provided dose-related decreases from baseline in HbA1c of -0.81% and -1.11%. Canagliflozin 100 and 300 mg decreased FPG (-1.5 and -2.2 mmol/L [-27.4 and -39.1 mg/dL]), body weight (-3.3% and -4.4%), and systolic BP (-1.4 and -3.9 mmHg); decreased triglycerides and increased HDL-C and LDL-C were also seen. Over 52 weeks, overall AE rates were 67.2%, 66.0%, and 64.1% with canagliflozin 100 and 300 mg and placebo/sitagliptin; rates of serious AEs and AE-related discontinuations were low across groups. Compared with placebo/sitagliptin, canagliflozin was associated with higher rates of genital mycotic infections and AEs related to osmotic diuresis; these led to few discontinuations. Rates of volume depletion AEs and documented hypoglycemia were low across groups.. Canagliflozin monotherapy provided sustained improvement in glycemic control and body weight reduction, and was generally well tolerated in patients with T2DM over 52 weeks.

Topics: Blood Glucose; Blood Pressure; Body Weight; Canagliflozin; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diet; Double-Blind Method; Exercise; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Middle Aged; Placebos; Pyrazines; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes; Treatment Outcome; Triazoles; Triglycerides; Weight Loss

We assessed the efficacy and safety of sitagliptin compared with α-glucosidase inhibitor (αGI) in 120 of Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on stable ≤2 mg/day glimepiride alone [mean hemoglobin A1c (HbA1c) 7.7%] by the randomized, active-controlled, non-inferiority trial. Patients were randomly assigned to receive additional sitagliptin or αGI for 24 weeks. The primary endpoint was change in HbA1c from baseline to week 12. After 12 weeks, sitagliptin reduced HbA1c by -0.44% (p < 0.001) relative to αGI. At 24 weeks, the reduction was almost identical between the groups (-0.091%, p = 0.47). Gastrointestinal disorders were more common with αGI than with sitagliptin, but only minor hypoglycaemia occurred in both groups at similar frequency. These data suggested that sitagliptin was not inferior to αGI for reduction of HbA1c in Japanese T2DM patients receiving glimepiride alone, and well tolerated with minimum risk of gastrointestinal symptoms and hypoglycaemia.

Topics: 1-Deoxynojirimycin; Aged; alpha-Glucosidases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Gastrointestinal Agents; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inositol; Japan; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Sulfonylurea Compounds; Triazoles

The aim of this study was to evaluate the safety and tolerability of sitagliptin 100 mg/day in elderly patients with type 2 diabetes.. A post hoc pooled analysis of 25 randomized, double-blind, parallel group clinical studies with results available as of 1 December 2011.. Multicenter, international clinical trials.. Patients with type 2 diabetes aged 65 years or older.. Patients were randomized to sitagliptin 100 mg/day (n = 1,261) or a comparator (n = 1,185) for 12 weeks to 2 years.. In each study, investigators reported serious and non-serious adverse events that occurred during the study, and serious adverse events occurring within 14 days following the last dose of study drug. This analysis used patient-level data from each study to assess the exposure-adjusted incidence rates of specific adverse events that occurred following initiation of study drug.. Summary measures of adverse events overall were similar between the sitagliptin and non-exposed (active comparator or placebo) groups, except for higher incidences of deaths and drug-related adverse events in the non-exposed group. Incidence rates of specific adverse events were generally similar between the two groups, with the exception of hypoglycemia. A lower incidence rate of hypoglycemia was observed in the sitagliptin group compared with the non-exposed group [7.0 vs. 14.3 per 100 patient-years; difference -7.6 (95 % CI -11.2 to -4.3]), primarily due to greater use of sulfonylureas in the non-exposed group.. In this pooled safety analysis of elderly patients with type 2 diabetes, treatment with sitagliptin 100 mg/day was generally well tolerated for up to 2 years.

Topics: Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Pyrazines; Sitagliptin Phosphate; Triazoles

The efficacy and safety of insulin degludec (IDeg), a new basal insulin with an ultra-long duration of action, was compared to sitagliptin (Sita) in a 26-week, open-label trial.. Insulin-naïve subjects with type 2 diabetes [n = 458, age: 56 years, diabetes duration: 7.7 years, glycosylated haemoglobin (HbA1c): 8.9% (74 mmol/mol)] were randomized (1 : 1) to once-daily IDeg or Sita (100 mg orally) as add-on to stable treatment with 1 or 2 oral antidiabetic drugs (OADs).. Superiority of IDeg to Sita in improving HbA1c and fasting plasma glucose (FPG) was confirmed [estimated treatment difference (ETD) IDeg-Sita for HbA1c: -0.43%-points [95% confidence interval (CI): -0.61; -0.24, p < 0.0001] and for FPG: -2.17 mmol/l (95% CI: -2.59; -1.74, p < 0.0001)]. HbA1c < 7% (<53 mmol/mol) was achieved by 41% (IDeg) versus 28% (Sita) of patients, estimated odds ratio IDeg/Sita: 1.60 (95% CI: 1.04; 2.47, p = 0.034). There was no statistically significant difference in the rate of nocturnal confirmed hypoglycaemia between IDeg and Sita [0.52 vs. 0.30 episodes/patient-year, estimated rate ratio (ERR): IDeg/Sita: 1.93 (95% CI: 0.90; 4.10, p = 0.09)]. Rates of overall confirmed hypoglycaemia were higher with IDeg than with Sita [3.1 vs. 1.3 episodes/patient-year, ERR IDeg/Sita: 3.81 (95% CI: 2.40; 6.05, p < 0.0001)]. IDeg was associated with a greater change in body weight than Sita [ETD IDeg-Sita: 2.75 kg (95% CI: 1.97; 3.54, p < 0.0001)]. The overall rates of adverse events were low and similar for both groups.. In patients unable to achieve good glycaemic control on OAD(s), treatment intensification with IDeg offers an effective, well-tolerated alternative to the addition of a second or third OAD.

Topics: Administration, Oral; Argentina; Blood Glucose; Body Weight; Canada; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; India; Insulin, Long-Acting; Male; Mexico; Middle Aged; Pyrazines; Sitagliptin Phosphate; South Africa; Treatment Outcome; Triazoles; Turkey; United States

This study investigated the safety and efficacy of sitagliptin (Januvia) for the inpatient management of type 2 diabetes (T2D) in general medicine and surgery patients.. In this pilot, multicenter, open-label, randomized study, patients (n = 90) with a known history of T2D treated with diet, oral antidiabetic agents, or low total daily dose of insulin (≤0.4 units/kg/day) were randomized to receive sitagliptin alone or in combination with glargine insulin (glargine) or to a basal bolus insulin regimen (glargine and lispro) plus supplemental (correction) doses of lispro. Major study outcomes included differences in daily blood glucose (BG), frequency of treatment failures (defined as three or more consecutive BG >240 mg/dL or a mean daily BG >240 mg/dL), and hypoglycemia between groups.. Glycemic control improved similarly in all treatment groups. There were no differences in the mean daily BG after the 1st day of treatment (P = 0.23), number of readings within a BG target of 70 and 140 mg/dL (P = 0.53), number of BG readings >200 mg/dL (P = 0.23), and number of treatment failures (P > 0.99). The total daily insulin dose and number of insulin injections were significantly less in the sitagliptin groups compared with the basal bolus group (both P < 0.001). There were no differences in length of hospital stay (P = 0.78) or in the number of hypoglycemic events between groups (P = 0.86).. Results of this pilot indicate that treatment with sitagliptin alone or in combination with basal insulin is safe and effective for the management of hyperglycemia in general medicine and surgery patients with T2D.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Triazoles

To assess the efficacy and safety of adding sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, in subjects with type 2 diabetes inadequately controlled with multiple daily insulin injections therapy (MDI). HbA1c, 1,5-anhydroglucitol (1,5-AG), body mass index (BMI), insulin doses, six-point self-measured plasma glucose (SMPG) profiles were assessed before, after 12 weeks, and after 24 weeks of MDI with 50 mg/day of sitagliptin in 40 subjects with type 2 diabetes. Safety endpoints included hypoglycemia and any adverse events. HbA1c significantly decreased during the first 12 weeks ( -0.64±0.60%), and was sustained over 24 weeks ( -0.69±0.85%). 1,5-AG increased significantly from 7.5±4.5 μg/mL at baseline to 9.6±5.5 μg/mL after 24 weeks. The bolus insulin dose at 12 weeks was decreased, and the mean plasma glucose, the SD of daily glucose, M-value, and the mean amplitude of glycemic excursions (MAGE) also decreased significantly as compared with baseline values. BMI and frequency of hypoglycemia were not changed significantly. Univariate linear regression analyses revealed that % change in HbA1c was significantly associated with BMI, and % changes in the indexes of glycemic instability (SD of daily glucose and MAGE) were significantly associated with age. In conclusion, adding sitagliptin to MDI significantly improved glycemic control and decreased the daily glucose fluctuation in subjects with type 2 diabetes inadequately controlled with MDI, without weight gain or an increase in the incidence of hypoglycemia. This trial was registered with UMIN (no. UMIN000010157).

Topics: Aged; Asian People; Blood Glucose; Blood Glucose Self-Monitoring; Body Mass Index; Deoxyglucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Triazoles

This study aimed to compare the effects of sitagliptin on glycemic change and 24-h blood glucose variability with those of the sulfonylurea glimepiride.. A 4-week randomized double blind-labeled prospective design was used. We recruited 33 patients who had been treated with metformin for at least 2 months. Each participant prescribed with metformin was randomly assigned to either the sitagliptin (100 mg) or the glimepiride (2 mg) group. Continuous glucose monitoring (CGM) was used to monitor glycemic changes for 3 successive days in both groups at baseline and at the 4-week follow-up. Glycemic changes and glucose variability were obtained using CGM, and these data were averaged over all subjects.. The comparison of glycated hemoglobin (HbA1c) between baseline and the 4-week follow-up showed that HbA1c was significantly reduced in the sitagliptin group (7.0 ± 0.5% to 6.6 ± 0.4%, P<0.001) and the glimepiride group (7.3 ± 0.4% to 6.9 ± 0.4%, P<0.001). The sitagliptin and glimepiride groups had similar HbA1c levels after 4 weeks, and there were no significant differences between the two groups. The mean amplitude of glycemic excursions (MAGE) decreased significantly in the sitagliptin group (4.9 ± 1.0 to 3.7 ± 0.9 mmol/L, P<0.001), but no significant difference was observed in the glimepiride group (5.7 ± 1.5 to 5.0 ± 1.4 mmol/L, P=0.175). The SD and oxidative stress markers did not differ significantly between the two groups.. When sitagliptin was combined with metformin, the patients showed much more efficient blood glucose controlling effects, not only the three indexes of fasting blood glucose, postprandial blood glucose, and glycated hemoglobin, but also MAGE.

Topics: Adult; Asian People; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Oxidative Stress; Patient Compliance; Prospective Studies; Pyrazines; Republic of Korea; Sitagliptin Phosphate; Sulfonylurea Compounds; Treatment Outcome; Triazoles

The aim of this research was to compare the pharmacodynamics of the combination of mitiglinide and sitagliptin to that of each agent alone in Korean patients with type 2 diabetes mellitus (T2DM).. Patients with T2DM received mitiglinide alone, sitagliptin alone, or both drugs together in randomized sequence. A meal tolerance test (MTT) was conducted for each group, and plasma concentrations of glucose, insulin, C-peptide, glucagon, and intact glucagon-like peptide-1, and dipeptidyl peptidase-4 activity were measured from 2 h before breakfast through 4 h after breakfast on day 0 (pretreatment) and day 1 (posttreatment) of each treatment period. Integrated values of these pharmacodynamic variables were analyzed for changes from pretreatment to posttreatment and for differences between the three treatment groups.. Twenty-six patients with glycated hemoglobin A1c level of 7.4% ± 0.6%, fasting plasma glucose concentration of 141 ± 22 mg/dL, postprandial plasma glucose (PPG) concentration of 264 ± 48 mg/dL 1 h after the MTT, and diabetes duration of 3.0 ± 3.1 years (mean ± SD) were included in the study. Compared with mitiglinide or sitagliptin alone, the combination treatment lowered PPG additively (P < 0.001 vs. mitiglinide or sitagliptin alone) and the insulin secretory response (P = 0.03 vs. mitiglinide or sitagliptin alone). The integrated insulin concentrations changed significantly from before to after treatment (P < 0.01), but the change did not differ between the combination and mitiglinide groups. The insulinogenic index increased significantly after the combination treatment (P < 0.001 vs. mitiglinide or sitagliptin alone). The combination of mitiglinide and sitagliptin was generally well tolerated, with no hypoglycemic events.. The combination of mitiglinide and sitagliptin did not trigger hypoglycemia and controlled postprandial glucose excursion more effectively compared with either drug alone.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Confidence Intervals; Cross-Over Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Isoindoles; Male; Middle Aged; Postprandial Period; Prospective Studies; Pyrazines; Reference Values; Severity of Illness Index; Sitagliptin Phosphate; Treatment Outcome; Triazoles

Basal-supported oral therapy (BOT) is often used to treat poorly controlled type 2 diabetes. However, patients sometimes experience nocturnal and early morning hypoglycemia. Thus, maintaining targeted glycemic control by BOT is limited in some patients. We assessed the efficacy and safety of replacing basal insulin by sitagliptin therapy in Japanese type 2 diabetes patients on BOT. Forty-nine subjects were sequentially recruited for the 52-week, prospective, single arm study. Patients on BOT therapy were switched from basal insulin to sitagliptin. The primary endpoint was change in HbA1c in 52 weeks. The secondary endpoints were dropout rate, changes in body weight, frequency of hypoglycemia, and relationship between change in HbA1c and insulin secretion capacity evaluated by glucagon loading test. The average dose of basal insulin was 15.0±8.4 units. Sixteen subjects (31.3%) were dropped because replacement by sitagliptin was less effective for glycemic control. In these subjects, diabetes duration was longer, FPG and HbA1c at baseline were higher, and insulin secretion capacity was lower. Change in HbA1c in 52 weeks was - 4 mmol/mol (95% CI - 5 to - 4 mmol/mol) (p<0.05). Change in body weight was - 0.71 kg (95% CI - 1.42 to - 0.004 kg) (p<0.05). Frequency of hypoglycemia was decreased from 1.21±1.05 to 0.06±0.24 times/month. HbA1c level was improved if C-peptide index (CPI) was over 1.19. In conclusion, basal insulin in BOT can be replaced by sitagliptin with a decrease in HbA1c level and frequency of hypoglycemia in cases where insulin secretion capacity was sufficiently preserved.

Topics: Aged; Asian People; Body Mass Index; Body Weight; C-Peptide; Demography; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Japan; Male; Pyrazines; ROC Curve; Sitagliptin Phosphate; Treatment Outcome; Triazoles

To test the hypothesis that glycaemic control achieved when switching sitagliptin to exenatide twice daily plus metformin is non-inferior to adding exenatide twice daily to sitagliptin and metformin.. Patients with Type 2 diabetes inadequately controlled with sitagliptin plus metformin were randomly assigned to 20 weeks of treatment with twice-daily exenatide plus placebo and metformin (SWITCH, n = 127) or twice-daily exenatide plus sitagliptin and metformin (ADD, n = 128).. Non-inferiority (0.4% margin) of SWITCH to ADD treatment, measured by change in HbA(1c) from baseline to week 20, was not shown {between-treatment difference in least-squares mean [95% CI 3 mmol/mol (0.30%)] [0.8-5.8 (0.07-0.53)]}. A greater reduction (P = 0.012) in HbA(1c) [least-squares mean (se)] was experienced by patients in the ADD group {-7 mmol/mol [-0.68%] [0.9 (0.08)]}, compared with those in the SWITCH group {-4 mmol/mol [-0.38%] [1.0 (0.09)]} and a greater proportion (P = 0.027) of patients in the ADD group (41.7%) reached < 7.0% (< 53 mmol/mol) HbA(1c) target, compared with those in the SWITCH group (26.6%) by week 20. Patients in the ADD group experienced greater fasting serum glucose (P = 0.038) and daily mean postprandial self-monitored blood glucose (P = 0.048) reductions, compared with patients in the SWITCH group, by week 20. Patients in both groups experienced a lower incidence of nausea and vomiting compared with previous exenatide studies.. Non-inferiority of SWITCH to ADD treatment was not supported by the results of this study. In patients with Type 2 diabetes inadequately controlled with sitagliptin plus metformin, adding exenatide provided better glycaemic control than switching to exenatide. These results are consistent with the clinical approach that adding is better than switching to another oral anti-hyperglycaemic medication.

Topics: Adolescent; Adult; Aged; Argentina; Australia; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Administration Schedule; Exenatide; Female; Germany; Glycated Hemoglobin; Greece; Humans; Hypoglycemia; Hypoglycemic Agents; India; Male; Metformin; Mexico; Middle Aged; Peptides; Pyrazines; Republic of Korea; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Venoms

Individuals requiring insulin therapy for type 2 diabetes often require escalation of their regimen to achieve glycaemic control. Optimal management strategies for uncontrolled type 2 diabetes would improve glycaemic control without hypoglycaemia and weight gain. This study compared the efficacy and tolerability of adding sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, and an up to 20% increase in insulin dose in patients with uncontrolled type 2 diabetes on insulin therapy.. We conducted a 24-week, randomized, active-competitor, parallel-group study in subjects with uncontrolled type 2 diabetes [haemoglobin A1c (HbA1c) = 7.5-11%] currently using insulin therapy. Subjects were randomly assigned to either the sitagliptin adding (100 mg daily, n = 70) or an insulin-increasing arm (≥ 10% at week 12 and ≥ 10% at week 24, n = 70) while continuing other medications.. Average baseline HbA1c was 9.2% in both groups. HbA1c decreased more at 24 weeks in the sitagliptin adding than the insulin-increasing arm (-0.6 ± 0.1% vs. -0.2 ± 0.1%, p < 0.01). Insulin was increased by 25% at 24 weeks in the insulin-increasing group. Hypoglycaemic events were less common and less severe in sitagliptin adding arm than insulin-increasing arm (7.0 vs. 14.3 events per patient-year, p < 0.05). Weight was stable in the sitagliptin adding subjects (68.6 ± 11.6 vs. 68.1 ± 11.4 kg) but increased in the insulin-increasing subjects (66.2 ± 10.6 vs. 67.4 ± 9.7 kg, p < 0.05). Other adverse events occurred at similar rates in both arms.. Compared to a 25% increase in insulin dose, adding sitagliptin to an insulin-based regimen was more effective at lowering HbA1c and associated with less hypoglycaemia and weight gain over 24 weeks.. NCT01100125.

Topics: Adult; Aged; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Triazoles; Waist Circumference

To assess the efficacy and safety of combination therapy with sitagliptin and low dosage sulphonylureas on glycaemic control and insulin secretion capacity in Japanese type 2 diabetes.. Eighty-two subjects were sequentially recruited for the 52-week, prospective, single arm study. Sitagliptin was added on to sulphonylureas (glimepride or gliclazide) with or without metformin. The primary endpoint was a change in A1C. The secondary endpoints were changes in BMI, insulin secretion capacity, blood pressure and urinary albumin excretion, unresponsive rate, and hypoglycaemia. Insulin secretion capacity was evaluated by glucagon loading test.. Change in A1C was -0.80% (95% CI -0.90 to -0.68) (p < 0.001). Change in BMI, systemic and diastolic blood pressure, and urinary albumin excretion were -0.38 kg/m(2) (95% CI -0.72 to -0.04) (p < 0.05), -6.7/-3.6 mmHg (95% CI -10.0 to -3.4/-4.8 to -2.4) (p < 0.001), and -43.2 mg/gCr (95% CI -65.7 to -20.8) (p < 0.001) respectively. Mild hypoglycaemia was observed in three cases. The unresponsive rate was 6.1%. Glucagon loading test showed that 0-min and 6-min CPR at baseline and 52-week were not significantly changed: 0-min CPR, 1.58 ± 0.58-1.71 ± 0.73 ng/ml; 6-min CPR, 3.48 ± 1.47-3.58 ± 1.21 ng/ml. Insulin secretion capacity, CPI and SUIT index at baseline did not predict the efficacy of the combination therapy. The final dosages of glimepiride and gliclazide were 1.44 ± 0.90 mg and 34.5 ± 15.3 mg respectively. The dosage of sitagliptin was increased from 50 mg to 69.0 ± 24.5 mg in 52-week.. The combination therapy with sitagliptin and low dosage sulphonylureas was safe and effective for glycaemic control. Glucagon loading test indicated that 1 year administration of sitagliptin and sulphonylureas preserved insulin secretion capacity.

Topics: Aged; Albuminuria; Blood Glucose; Blood Pressure; Body Mass Index; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Middle Aged; Prospective Studies; Pyrazines; Sitagliptin Phosphate; Sulfonylurea Compounds; Treatment Outcome; Triazoles

To compare the incidence of symptomatic hypoglycemia between sitagliptin and sulfonylurea in Muslim patients with type 2 diabetes who fasted during Ramadan.. In a multicenter, pragmatic, randomized study, patients with type 2 diabetes were recruited from clinical centers in India (n = 765) and Malaysia (n = 105). Eligible patients (age ≥ 18 yrs) expressed their intention to daytime fast during Ramadan, were treated with a stable dose of sulfonylurea with or without metformin for ≥3 months prior to screening visit, and had an HbA(1c) ≤ 10%. Patients were randomized in a 1:1 ratio to either switch to sitagliptin 100 mg q.d. or remain on their pre-study sulfonylurea. Daily diary cards were completed to document information on hypoglycemic symptoms and complications. The primary endpoint was the overall incidence of symptomatic hypoglycemia during Ramadan.. Of the 870 patients randomized, 848 (n = 421 for sitagliptin and 427 for sulfonylurea) returned ≥1 completed diary card and were included in the analysis. The proportion of patients who recorded ≥1 symptomatic hypoglycemic event during Ramadan was lower with sitagliptin (3.8%) compared to sulfonylurea (7.3%). The risk of symptomatic hypoglycemia was significantly lower with sitagliptin (risk ratio [95% CI] = 0.52 [0.29, 0.94]; p = 0.028). By country, the proportions of patients who recorded ≥1 symptomatic hypoglycemic event during Ramadan were 4.1% vs. 7.7% in India and 1.9% vs. 3.8% in Malaysia for sitagliptin and sulfonylurea, respectively. No patient discontinued treatment due to a hypoglycemic event. One patient on sitagliptin and seven on sulfonylurea had an event that required non-medical assistance. No events required medical assistance. Both treatments were generally well tolerated.. Symptomatic hypoglycemic events did not require a confirmatory blood glucose measurement, which may have overestimated hypoglycemic events. Measures of glycemic control and body weight were not assessed.. Switching antihyperglycemic treatment to sitagliptin from a sulfonylurea reduced the risk of symptomatic hypoglycemia by approximately 50% for Muslim patients with type 2 diabetes who fasted during Ramadan.. Clinicaltrials.gov: NCT01340768.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Female; Humans; Hypoglycemia; Hypoglycemic Agents; India; Islam; Malaysia; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Sulfonylurea Compounds; Triazoles; Young Adult

to evaluate the efficacy and safety of adding sitagliptin or glimepiride to the treatment regimen of patients with type 2 diabetes mellitus and inadequate glycaemic control on metformin monotherapy.. patients with type 2 diabetes and an HbA(1c) of 6.5-9.0% while on a stable dose of metformin (≥ 1500 mg/day) combined with diet and exercise for at least 12 weeks were randomized in a double-blind manner to receive either sitagliptin 100 mg daily (N = 516) or glimepiride (starting dose 1 mg/day and up-titrated, based upon patient's self-monitoring of blood glucose results, to a maximum dose of up to 6 mg/day) (N = 519) for 30 weeks. The primary analysis assessed whether sitagliptin is non-inferior to glimepiride in reducing HbA(1c) at week 30 (based on the criterion of having an upper bound of the 95% CI less than the prespecified non-inferiority bound of 0.4%).. the mean baseline HbA(1c) was 7.5% in both the sitagliptin group (n = 443) and the glimepiride group (n = 436). After 30 weeks, the least squares (LS) mean change in HbA(1c) from baseline was -0.47% with sitagliptin and -0.54% with glimepiride, with a between-group difference (95% CI) of 0.07% (-0.03, 0.16). This result met the prespecified criterion for declaring non-inferiority. The percentages of patients with an HbA(1c) < 7.0% at week 30 were 52 and 60% in the sitagliptin and glimepiride groups, respectively. The LS mean change in fasting plasma glucose from baseline (95% CI) was -0.8 mmol/l (-1.0, -0.6) with sitagliptin and -1.0 mmol/l (-1.2, -0.8) with glimepiride, for a between-group difference (95% CI) of 0.2 mmol/l (-0.1, 0.4). The percentages of patients for whom hypoglycaemia was reported were 7% in the sitagliptin group and 22% in the glimepiride group (percentage-point difference = -15, p < 0.001). Relative to baseline, sitagliptin was associated with a mean weight loss (-0.8 kg), whereas glimepiride was associated with a mean weight gain (1.2 kg), yielding a between-group difference of -2.0 kg (p < 0.001).. in patients with type 2 diabetes and inadequate glycaemic control on metformin monotherapy, the addition of sitagliptin or glimepiride led to similar improvement in glycaemic control after 30 weeks. Sitagliptin was generally well tolerated. Compared to treatment with glimepiride, treatment with sitagliptin was associated with a lower risk of hypoglycaemia and with weight loss versus weight gain (ClinicalTrials.gov: NCT00701090).

Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Pyrazines; Sitagliptin Phosphate; Sulfonylurea Compounds; Treatment Outcome; Triazoles

The aim of this trial was to evaluate the efficacy and safety of the combination of once-daily insulin detemir (IDet) and sitagliptin (SITA) versus SITA ± sulphonylurea (SU), both in combination with metformin (MET) in insulin-naive subjects.. In a 26-week, open-label, randomized, parallel-group study in type 2 diabetes, insulin-naive subjects concomitantly treated with MET ± second oral antidiabetic drug (OAD) were randomized 1 : 1 to IDet + SITA + MET or SITA + MET ± SU. All continued with MET treatment, and those treated with SU continued if randomized to SITA + MET ± SU. Efficacy endpoints included glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), 9-point self-measured plasma glucose (SMPG), weight, body mass index (BMI). Safety endpoints included adverse events (AEs) and hypoglycaemia.. Significantly higher reductions in HbA1c, FPG and SMPG were achieved with IDet + SITA + MET compared with SITA + MET ± SU. Estimated HbA1c decreased by 1.44% in the IDet + SITA + MET group versus 0.89% in SITA + MET ± SU, p < 0.001. FPG decreased by 3.7 mmol/l (66.3 mg/dl) versus 1.2 mmol/l (22.2 mg/dl), p < 0.001, respectively. Small decreases in weight and BMI were observed in both arms, with no significant differences. AEs were mild or moderate and were more common in the SITA + MET ± SU arm than in the IDet + SITA + MET arm. There was no major hypoglycaemia. Observed rates of hypoglycaemia were very low (1.3/1.7 episodes/patient year) in both arms. The subgroup treated with MET and SUs prior to the trial achieved similar results.. The combination of once-daily IDet with SITA showed a clinically and significantly better improvement in glycaemic control than SITA in combination with or without SUs. Both regimens were associated with a low rate of hypoglycaemia and slight weight reduction.

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Metformin; Middle Aged; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Weight Loss

Sitagliptin and glipizide added to metformin provided similar degrees of glycemic efficacy in patients with type 2 diabetes with inadequate glycemic control on metformin monotherapy at 1 year; however, significantly more patients in the sitagliptin group achieved an A1C reduction of >0.5% without hypoglycemia and without an increase in body weight.

Topics: Aged; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Female; Glipizide; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Pyrazines; Sitagliptin Phosphate; Triazoles; Weight Gain

This study was performed to examine the efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes using continuous glucose monitoring (CGM) of 24-h glycemic changes.. The study was a prospective open-label pilot study in patients with type 2 diabetes who were admitted to our hospital and treated with sitagliptin alone or concomitantly with another oral hypoglycemic drug. CGM was performed for 2 days before sitagliptin administration and for another 2 days after administration. The average 24-h blood glucose level, SD of the 24-h blood glucose level, 24-h glycemic fluctuation range, mean amplitude of glycemic excursions (MAGE), and hyperglycemic and hypoglycemic time periods were compared before and after administration.. Sitagliptin administration alone and with a concomitant drug decreased the average 24-h blood glucose level, SD of the 24-h blood glucose level, 24-h glycemic fluctuation range, MAGE, and hyperglycemic time, compared with these parameters before administration. There were significant correlations between the average 24-h blood glucose level before administration and the decrease in the average 24-h blood glucose level after administration and between MAGE before administration and the decrease in MAGE after administration.. Sitagliptin decreased the average glycemic level and also improved 24-h glycemic fluctuation, including postprandial hyperglycemia.

Topics: Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Homeostasis; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Japan; Male; Middle Aged; Monitoring, Ambulatory; Pilot Projects; Postprandial Period; Pyrazines; Sitagliptin Phosphate; Triazoles

To compare the incidence of symptomatic hypoglycaemia in fasting Muslim patients with type 2 diabetes treated with sitagliptin or a sulphonylurea during Ramadan.. Patients with type 2 diabetes (age ≥ 18 years) who were treated with a stable dose of a sulphonylurea with or without metformin for at least 3 months prior to screening, who had an HbA(1c) < 10% and who expressed their intention to daytime fast during Ramadan were eligible for this open-label study. Patients were randomised in a 1 : 1 ratio to either switch to sitagliptin 100 mg qd or to remain on their prestudy sulphonylurea. Patients completed daily diary cards to document information on hypoglycaemic symptoms and complications. The primary end-point was the overall incidence of symptomatic hypoglycaemia recorded during Ramadan.. Of the 1066 patients randomised, 1021 (n = 507 for sitagliptin and n = 514 for sulphonylurea) returned at least one completed diary card and were included in the analysis. The proportion of patients who recorded one or more symptomatic hypoglycaemic events during Ramadan was lower in the sitagliptin group (6.7%) compared with the sulphonylurea group (13.2%). The risk of symptomatic hypoglycaemia was significantly decreased with sitagliptin relative to sulphonylurea treatment (Mantel-Haenszel relative risk ratio [95% CI] = 0.51 [0.34, 0.75]; p < 0.001). There were no reported events that required medical assistance (i.e. visits to physician or emergency room or hospitalisations) or were considered severe (i.e. events that caused loss of consciousness, seizure, coma or physical injury) during Ramadan.. In Muslim patients with type 2 diabetes who observed the fast during Ramadan, switching to a sitagliptin-based regimen decreased the risk of hypoglycaemia compared with remaining on a sulphonylurea-based regimen. The incidence of hypoglycaemia was lower with gliclazide relative to the other sulphonylurea agents and similar to that observed with sitagliptin.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Drug Substitution; Fasting; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Islam; Male; Middle Aged; Middle East; Pyrazines; Residence Characteristics; Sitagliptin Phosphate; Sulfonylurea Compounds; Triazoles; Young Adult

To assess the efficacy and safety of a 24-week treatment with sitagliptin, a highly selective once-daily oral dipeptidyl peptidase-4 (DPP-4) inhibitor, in patients with type 2 diabetes who had inadequate glycaemic control [glycosylated haemoglobin (HbA(1c)) >or=7.5% and or=4 mg/day) monotherapy and 229 were on glimepiride (>or=4 mg/day) plus metformin (>or=1,500 mg/day) combination therapy. Patients exceeding pre-specified glycaemic thresholds during the double-blind treatment period were provided open-label rescue therapy (pioglitazone) until study end. The primary efficacy analysis evaluated the change in HbA(1c) from baseline to Week 24. Secondary efficacy endpoints included fasting plasma glucose (FPG), 2-h post-meal glucose and lipid measurements.. Mean baseline HbA(1c) was 8.34% in the sitagliptin and placebo groups. After 24 weeks, sitagliptin reduced HbA(1c) by 0.74% (p < 0.001) relative to placebo. In the subset of patients on glimepiride plus metformin, sitagliptin reduced HbA(1c) by 0.89% relative to placebo, compared with a reduction of 0.57% in the subset of patients on glimepiride alone. The addition of sitagliptin reduced FPG by 20.1 mg/dl (p < 0.001) and increased homeostasis model assessment-beta, a marker of beta-cell function, by 12% (p < 0.05) relative to placebo. In patients who underwent a meal tolerance test (n = 134), sitagliptin decreased 2-h post-prandial glucose (PPG) by 36.1 mg/dl (p < 0.001) relative to placebo. The addition of sitagliptin was generally well tolerated, although there was a higher incidence of overall (60 vs. 47%) and drug-related adverse experiences (AEs) (15 vs. 7%) in the sitagliptin group than in the placebo group. This was largely because of a higher incidence of hypoglycaemia AEs (12 vs. 2%, respectively) in the sitagliptin group compared with the placebo group. Body weight modestly increased with sitagliptin relative to placebo (+0.8 vs. -0.4 kg; p < 0.001).. Sitagliptin 100 mg once daily significantly improved glycaemic control and beta-cell function in patients with type 2 diabetes who had inadequate glycaemic control with glimepiride or glimepiride plus metformin therapy. The addition of sitagliptin was generally well tolerated, with a modest increase in hypoglycaemia and body weight, consistent with glimepiride therapy and the observed degree of glycaemic improvement.

Topics: Adolescent; Adult; Aged; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Pyrazines; Single-Blind Method; Sitagliptin Phosphate; Sulfonylurea Compounds; Treatment Outcome; Triazoles

Management of diabetes during fasting is a clinical challenge. Sodium glucose co-transporter -2 inhibitors (SGLT2i) are considered safe with a low risk of hypoglycemia. However, studies on SGLT2i are scarce. This study was designed to compare the efficacy, safety, and tolerability of empagliflozin with metformin during Ramadan in comparison with sitagliptin and metformin.. It was a prospective, observational study, conducted at 11 different sites all across Pakistan on an outpatient basis during Ramadan (May 2021-June 2021). including 132 patients, 88 who received metformin and sitagliptin, and 44 patients who received metformin and empagliflozin.. Patients of the SGLT-2i group experienced similar symptomatic hypoglycemic episodes (15.9%) as the sitagliptin group. There was an improvement in blood sugar levels after the use of SGLT-2i (RBS 181 ± 64 before Ramadan vs 162 ± 53 after Ramadan). HbA1c also improved after the use of SGLT-2i before and after Ramadan (7.2 ± 0.8 vs 6.9 ± 0.9 for Metformin + Empagliflozin and 7.8 ± 1.5 vs 7.6 ± 1.6 for Metformin and sitagliptin). Weight and BMI improved after the use of SGLT-2i (BMI 36.5 ± 4.8 before Ramadan and 33.7 ± 2.4 after Ramadan). There were no reported cases of urinary tract infection in the empagliflozin group.. SGLT-2 inhibitors combined with metformin for patients with diabetes during Ramadan fasting is as effective, safe and well tolerated as DPP4 combined with metformin.

Topics: Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Drug Therapy, Combination; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Metformin; Prospective Studies; Sitagliptin Phosphate; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters

To compare the efficacy and safety of an initial triple therapy using metformin, a dipeptidyl peptidase-4 (DPP4) inhibitor, and thiazolidinedione with a stepwise approach using sulfonylurea and metformin in new-onset, drug-naïve patients with type 2 diabetes.. Among drug-naïve patients with 9.0%-12.0% glycated hemoglobin (HbA1c) but no hyperglycemic symptoms, 100 subjects who started triple medications (metformin 1000 mg/day, sitagliptin 100 mg/day, and lobeglitazone 0.5 mg/day) were selected as an initial triple therapy group. Age and body mass index-matched subjects (n=100) who started glimepiride (≥2 mg/day with uptitration) and metformin (≥1000 mg/day with uptitration) were selected as a conventional therapy group. We investigated changes in HbA1c level, dynamic indexes for insulin sensitivity and β-cell function, and hypoglycemia.. After 12 months of treatment, HbA1c levels decreased significantly in both groups: from 10.7%±1.0% to 6.7%±1.3% in the triple group, and from 10.5%±1.0% to 7.3%±1.2% in the conventional therapy group. At 12 months, achievement of the HbA1c target (<7.0%) was higher in the triple group than in the conventional group (70% vs 52%, p<0.01). Dynamic indexes related to β-cell function and insulin sensitivity improved, and albuminuria reduced significantly only in the triple group. Hypoglycemia was more common in the conventional group.. Initial triple combination therapy with the DPP4 inhibitor, metformin, and thiazolidinedione showed a higher achievement of the target HbA1c goal with a lower risk of hypoglycemia, better restoration of β-cell function, and multiple metabolic benefits, implying durable glycemic control. This strategy may be useful for patients presenting with type 2 diabetes and high HbA1c levels.

Topics: Biomarkers; Blood Glucose; Case-Control Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Resistance; Male; Metformin; Middle Aged; Prognosis; Pyrimidines; Republic of Korea; Sitagliptin Phosphate; Thiazolidinediones

Oral semaglutide is the first orally administered glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes, and has been evaluated in the PIONEER clinical trial program. These trials assessed the proportions of patients achieving single and composite endpoints, encompassing glycemic control [defined in terms of glycated hemoglobin (HbA1c)], weight loss, and hypoglycemia. The present study assessed the cost of control with oral semaglutide versus empagliflozin, sitagliptin, and liraglutide in the US.. Four endpoints were evaluated: (1) HbA1c ≤ 6.5%; (2) HbA1c < 7.0%; (3) ≥ 1.0%-point HbA1c reduction and weight loss ≥ 3.0%; and (4) HbA1c < 7.0% without hypoglycemia and without weight gain. The proportions of patients achieving each endpoint were sourced from the PIONEER 2, 3 and 4 trials. Treatment costs were accounted over an annual time-period in 2019 US dollars (USD), based on wholesale acquisition cost. Cost of control was calculated by dividing treatment costs by the proportion of patients achieving each target.. Oral semaglutide was consistently associated with the lowest cost of control for all four endpoints. For the targets of HbA1c ≤ 6.5% and HbA1c < 7.0%, oral semaglutide 14 mg was associated with lower cost of control than empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg by USD 15,036, 14,697, and 6996, respectively, and USD 931, 346 and 4497, respectively. For the double composite endpoint, cost of control was lower with oral semaglutide 14 mg by USD 525, 32,277 and 13,011, respectively versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg. For the triple composite endpoint, cost of control was lower with oral semaglutide 14 mg by USD 1255, 7510 and 5774, respectively.. Oral semaglutide was associated with lower cost of bringing patients with type 2 diabetes to four clinically-relevant treatment targets versus empagliflozin, sitagliptin, and liraglutide in the US.. Novo Nordisk A/S.

Topics: Benzhydryl Compounds; Blood Glucose; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Glucagon-Like Peptides; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Middle Aged; Sitagliptin Phosphate; United States; Weight Loss

To investigate the efficacy and safety of sitagliptin in elderly patients with type 2 diabetes mellitus, with a focus on hypoglycemia.. Type 2 diabetes mellitus patients who started sitagliptin therapy and were followed for 52 weeks were enrolled in the Impact of Sitagliptin on Diabetes Mellitus in Japanese Elderly Patients study. The frequency of hypoglycemia and knowledge of hypoglycemia were analyzed using a questionnaire.. In total, 5,130 patients (aged 73.8 ± 6.1 years) were analyzed. A significant reduction in glycated hemoglobin (-0.7 ± 1.1%, P < 0.001) and glycoalbumin levels (-2.2 ± 3.8%, P < 0.001) was observed at week 52. The percentage of patients with hypoglycemia did not increase from the baseline (3.3%) to week 52 (2.8%) of sitagliptin administration. Hypoglycemia incidence was significantly higher for combination therapy with insulin (odds ratio 17.75, P < 0.001) or sulfonylurea (odds ratio 2.22, P < 0.001). The increase in sitagliptin dose for combination therapy with antidiabetic drug(s) increased the percentage of patients with hypoglycemia (5.6% in sitagliptin increased subgroup, 2.4% in sitagliptin maintained subgroup, P < 0.01). The awareness of hypoglycemia symptoms and attitude to carry glucose as a countermeasure to prevent hypoglycemia increased during the study.. Sitagliptin did not increase the percentage of patients with hypoglycemia among elderly patients with type 2 diabetes mellitus. However, hypoglycemia occurred more frequently in add-on therapy to sulfonylurea or when the sitagliptin dose was increased in combination therapy, showing that sitagliptin should be used with caution.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Prospective Studies; Sitagliptin Phosphate; Treatment Outcome

The morbidity of cardiovascular disease in patients with type 2 diabetes mellitus (DM) deteriorates in combination with dyslipidemia. The accumulation of remnant lipoproteins in patients with fasting and postprandial hypertriglyceridemia is highly atherogenic. The current study investigated whether the dipeptidyl peptidase-4 inhibitor sitagliptin ameliorates dyslipidemia and hyperglycemia.. We enrolled 38 patients with type 2 DM (20 males and 18 females, 65.7±9.9 years old, HbA1c levels ＜8.4%), and all patients gave written informed consent. Sitagliptin (50 mg/day) was added to current antidiabetic treatments and increased to 100 mg/day to achieve low HbA1c levels (＜7.4%). Glucose and lipoprotein metabolism profiles were analyzed at 0, 4, and 12 weeks after sitagliptin administration.. Sitagliptin significantly decreased fasting levels of triglyceride (TG) (161±90 vs. 130±66 mg/dl, p＜0.01) and non-HDL-C (129±29 vs. 116±20 mg/dl, p＜0.01) in combination with glucose (150±47 vs. 129±27 mg/dl, p＜0.01) and HbA1c (7.1±0.6 vs. 6.6±0.7 mg/dl, p＜0.001). Sitagliptin also significantly decreased the fasting levels of apolipoprotein (apo) B-48 (7.8±6.7 vs. 5.6±4.0 µg/ml, p＜0.01), remnant lipoprotein cholesterol (15.3±9.5 vs. 12.0±7.9 mg/dl, p＜0.05) and other apolipoproteins, such as apoB, apoC-II, apoC-III, and apoE. Analyses of the lipoprotein profiles of fasting sera revealed that sitagliptin significantly decreased cholesterol and TG levels of lipoprotein fractions in the size of very low density lipoprotein and low density lipoprotein.. These findings indicated that sitagliptin administration ameliorated the lipid and lipoprotein profiles in patients with diabetes, which may be due to the decrease in atherogenic remnant lipoproteins (UMIN#000013218).

Topics: Aged; Biomarkers; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Follow-Up Studies; Humans; Hyperglycemia; Hypoglycemia; Lipoproteins; Male; Prognosis; Prospective Studies; Sitagliptin Phosphate

The recent LIRA-SWITCH trial showed that switching from sitagliptin 100 mg to liraglutide 1.8 mg led to statistically significant and clinically relevant improvements in glycated haemoglobin (HbA1C) and body mass index (BMI). Based on these findings, the aim of the present study was to assess the long-term cost-effectiveness of switching from sitagliptin to liraglutide in patients with type 2 diabetes in the UK.. The IQVIA CORE Diabetes Model Version 8.5+ was used to project costs and clinical outcomes over patients' lifetimes. Baseline cohort characteristics and treatment effects were derived from the LIRA-SWITCH trial. Future costs and clinical benefits were discounted at 3.5% annually. Costs were accounted in pounds sterling (GBP) and expressed in 2016 values. One-way and probabilistic sensitivity analyses were performed.. Model projections showed improved quality-adjusted life expectancy for patients with poorly controlled HbA1c upon switching from sitagliptin to liraglutide, compared with continuing sitagliptin treatment (9.18 vs 9.02 quality-adjusted life years [QALYs]). Treatment switching was associated with increased overall costs (GBP 24737 vs GBP 22362). Higher pharmacy costs were partially offset by reduced diabetes-related complication costs in patients who switched to liraglutide. Switching to liraglutide was associated with an incremental cost-effectiveness ratio of GBP 15423 per QALY gained vs continuing with sitagliptin treatment.. Switching from sitagliptin 100 mg to liraglutide 1.8 mg in patients with poor glycaemic control was projected to improve clinical outcomes and is likely to be considered cost-effective in the UK setting and, therefore, a good use of limited NHS resources.

Topics: Anti-Obesity Agents; Body Mass Index; Cohort Studies; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Monitoring; Drug Resistance; Glucagon-Like Peptide-1 Receptor; Health Care Costs; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Models, Economic; Overweight; Quality of Life; Risk Factors; Sitagliptin Phosphate; United Kingdom; Weight Loss

The objective of the present study was to observe the effect of sitagliptin on obese patients with insulin treatment-induced diabetes mellitus.. A total of 120 obese patients with insulin treatment-induced diabetes mellitus were consecutively selected and divided into the control group (n=35), observation group 1 (n=40), and observation group 2 (n=45). The control group received different types or doses of insulin, observation group 1 received insulin combined with metformin, and observation group 2 received insulin combined with sitagliptin. The therapeutic effects were compared at the 6-month follow-up visit.. Body mass index (BMI) was lower in observation group 1 and observation group 2, and higher in the control group compared with before treatment; the occurrence of hypoglycemia in observation group 2 was lower than in the other two groups, and the differences were statistically significant (p<0.05). After treatment, the fasting insulin (FINS) and homeostatic model assessment insulin-resistance (HOMA-IR) in observation group 2 were significantly lower than in the other two groups (p<0.05). Adiponectin levels were increased and leptin and visfatin levels were decreased in observation group 2 after treatment, and the differences were statistically significant (p<0.05). The levels of fasting blood glucose, hemoglobin A1c, total cholesterol, triglyceride, and low-density lipoprotein in the three groups were not significantly different (p>0.05).. Sitagliptin can reduce BMI and the occurrence of hypoglycemia in obese patients with insulin treatment-induced diabetes mellitus, and the effect may be related to decreased HOMA-IR, decreased leptin and visfatin levels, and increased adiponectin levels.

Topics: Adiponectin; Adult; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Resistance; Leptin; Male; Metformin; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity; Sitagliptin Phosphate; Triglycerides

The effect of hypoglycemia on the progression of atherosclerosis in patients with type 2 diabetes mellitus (T2DM) remains largely unknown. This is a post hoc analysis of a randomized trial to investigate the relationship between hypoglycemic episodes and changes in carotid intima-media thickness (IMT). Among 274 study subjects, 104 patients experienced hypoglycemic episodes. Increases in the mean IMT and left maximum IMT of the common carotid arteries (CCA) were significantly greater in patients with hypoglycemia compared to those without hypoglycemia. Classification of the patients into three groups according to the frequency of hypoglycemic episodes showed that high frequency of hypoglycemic events was associated with increases in mean IMT-CCA, and left max-IMT-CCA and right max-IMT-CCA. In addition, repetitive episodes of hypoglycemia were associated with a reduction in the beneficial effects of sitagliptin on carotid IMT. Our data suggest that frequency of hypoglycemic episodes was associated with changes in carotid atherosclerosis.

Topics: Aged; Carotid Artery Diseases; Carotid Artery, Common; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Disease Progression; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulins; Male; Middle Aged; Risk Factors; Sitagliptin Phosphate

To assess resource utilization associated with severe hypoglycaemia across three insulin regimens in a large phase 3a clinical programme involving people with Type 1 diabetes treated with basal-bolus insulin, people with Type 2 diabetes treated with multiple daily injections and people with Type 2 diabetes treated with basal-oral therapy.. Data relating to severe hypoglycaemia events (defined as episodes requiring external assistance) from the insulin degludec and insulin degludec/insulin aspart programme (15 trials) were analysed using descriptive statistics. Comparators included insulin glargine, biphasic insulin aspart, insulin detemir and sitagliptin. Mealtime insulin aspart was used in some regimens. This analysis used the serious adverse events records, which documented the use of ambulance/emergency teams, a hospital/emergency room visit ≤ 24 h, or a hospital visit > 24 h.. In total, 536 severe hypoglycaemia events were analysed, of which 157 (29.3%) involved an ambulance/emergency team, 64 (11.9%) led to hospital/emergency room attendance of ≤ 24 h and 36 (6.7%) required hospital admission (> 24 h). Although there were fewer events in people with Type 2 diabetes compared with Type 1 diabetes, once a severe episode occurred, the tendency to utilize healthcare resources was higher in Type 2 diabetes vs. Type 1 diabetes. A higher proportion (47.6%) in the basal-oral therapy group required hospital treatment for > 24 h versus the Type 1 diabetes (5.0%) and Type 2 diabetes multiple daily injections (5.3%) groups.. This analysis suggests that severe hypoglycaemia events often result in emergency/ambulance calls and hospital treatment, incurring a substantial health economic burden, and were associated with all insulin regimens.

Topics: Administration, Oral; Adult; Clinical Trials, Phase III as Topic; Cohort Studies; Costs and Cost Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Health Care Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Severity of Illness Index; Sitagliptin Phosphate

BackgroundCanagliflozin, an agent that inhibits sodium glucose co-transporter 2, is approved as add-on to metformin plus sulfonylurea for the treatment of type 2 diabetes in Canada. Canagliflozin offers greater glycemic control, as well as important additional benefits such as weight loss and blood pressure reductions, versus dipeptidyl peptidase-4 inhibitors such as sitagliptin.  ObjectiveThis analysis evaluated the cost-effectiveness of canagliflozin 300 mg and canagliflozin 100 mg versus sitagliptin 100 mg in patients with type 2 diabetes inadequately controlled on metformin plus sulfonylurea from the perspective of the Canadian Agency for Drugs and Technologies in Health. MethodsA 40-year cost-effectiveness analysis was performed using the validated Economic and Health Outcomes Model of Type 2 Diabetes Mellitus (ECHO-T2DM). Patient characteristics, treatment effects, and rates of hypoglycemia and adverse events were sourced from the canagliflozin clinical program. Canada-specific costs and utilities were applied. Sensitivity analyses were conducted using alternative values for key model inputs. ResultsBoth canagliflozin 300 and 100 mg dominated sitagliptin 100 mg over 40 years, providing quality-adjusted life-year gains of 0.31 and 0.28, and cost offsets of $2,217 and $2,560, respectively. Both canagliflozin doses dominated sitagliptin in each of the sensitivity analyses. ConclusionsSimulation results suggested that canagliflozin 300 and 100 mg provided better health outcomes and lower costs than sitagliptin 100 mg as a third-line therapy added-on to metformin and sulfonylurea in patients with type 2 diabetes in Canada.

Topics: Aged; Blood Glucose; Canada; Canagliflozin; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Models, Econometric; Quality-Adjusted Life Years; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Sulfonylurea Compounds

There have only been a few reports about use of dipeptidyl peptidase 4 (DPP-4) inhibitors in elderly patients with type 2 diabetes mellitus (T2DM), suggesting that the safety of these agents has not been sufficiently demonstrated. We performed a comparative review of the efficacy and safety of sitagliptin for Japanese patients with T2DM managed in the real-world clinical setting.. An age-stratified analysis was performed of 831 patients who were treated with sitagliptin for 2 years. Parameters assessed included the hemoglobin A1c (HbA1c), body weight, serum creatinine, and adverse events. HbA1c and the incidence of hypoglycemia were also evaluated in patients treated with sitagliptin and a sulfonylurea (SU), who were divided into three age groups (<65 years, 65-74 years, and ≥75 years).. Comparison of glycemic control parameters, laboratory values, and adverse events revealed significant improvement of HbA1c, casual postprandial plasma glucose, and fasting plasma glucose in each age group with no change in body weight. Serum creatinine increased significantly in all age groups. Hypoglycemia only occurred in patients who received combined treatment with an SU and sitagliptin, and there was no age-related difference in its incidence.. HbA1c was improved by 2 years of sitagliptin therapy in all three age groups, and age did not seem to influence the incidence of hypoglycemic events. These results confirm the efficacy and safety of sitagliptin in patients ≥ 75 years old, suggesting that it is also useful for treating elderly patients with T2DM.

Topics: Aged; Cohort Studies; Creatinine; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Japan; Male; Middle Aged; Retrospective Studies; Sitagliptin Phosphate; Sulfonylurea Compounds; Treatment Outcome

The aim of this study was to investigate whether the positive effects of sitagliptin were maintained even after five years of treatment. Starting from 2008 to today, we treated 624 patients, not well controlled by current therapy, with the addition of sitagliptin 100 mg/die. Patients included 216 subjects treated with metformin, 206 treated with sulfonylureas, and 202 treated with pioglitazone. Sitagliptin was added to metformin, sulfonylureas and pioglitazone in monotherapy, respectively, and the data were compared with those of 620 patients treated with sulfonylureas+metformin, pioglitazone+metformin and pioglitazone+sulfonylureas matched for age, sex, diabetes duration. We recorded that the addition of sitagliptin to current hypoglycemic therapy led to a reduction of HbA1c similar to that obtained with sulfonylureas after two years. After five years of treatment, changes in HbA1c suggest a better glycemic control over the long term with sitagliptin compared to other treatments, particularly when compared with sulfonylureas. The other parameters evaluated as fasting plasma glucose, post-prandial plasma glucose and insulin levels, confirm the trends observed for the value of HbA1c. Regarding BMI, it increased with sulfonylureas and pioglitazone compared to sitagliptin. Patients treated with sulfonylureas had a higher incidence of hypoglycemia compared to sitagliptin. In conclusion, sitagliptin seems to maintain its positive effects on glycemia and fasting plasma insulin on the long term.

Topics: Adolescent; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Pioglitazone; Sitagliptin Phosphate; Thiazolidinediones

Hypoglycemia due to treatment with oral anti-hyperglycemic agents (OHAs) is a major clinical problem in patients with type 2 diabetes mellitus. The aim of the present study was to evaluate the risk of hypoglycemia due to OHA use by using the Japanese Adverse Drug Event Report (JADER) database. To this end, reports of hypoglycemia events included in the JADER database between 2004 and 2012 were analyzed by calculating the reporting odds ratio (OR). The Medical Dictionary for Regulatory Activities Preferred Terms was used to identify hypoglycemia; 254392 reports were found in the JADER database, of which 13269 were excluded because the age and sex of the patient were not reported. Finally, 241123 reports were analyzed. Among OHAs, sulfonylureas showed the highest adjusted OR (adjusted OR, 10.13; 95% confidence interval, 9.08-11.26). The adjusted ORs for meglitinides, biguanide, thiazolidinedione, alpha-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors were significantly lower than that of sulfonylureas. The adjusted OR of meglitinides (3.17; 95% confidence interval, 2.23-4.36) was significantly higher than that of alpha-glucosidase inhibitors or thiazolidinedione. We observed no difference between the adjusted ORs for biguanide, thiazolidinedione, alpha-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors. Data mining of the JADER database was useful for analyzing OHA-associated hypoglycemia events. The results of our study suggested a low risk of hypoglycemia associated with biguanide, thiazolidinedione, alpha-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors in clinical practice.

Topics: Acarbose; Administration, Oral; Adverse Drug Reaction Reporting Systems; Benzamides; Biguanides; Data Mining; Databases, Pharmaceutical; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Japan; Pyrazines; Risk; Sitagliptin Phosphate; Sulfonylurea Compounds; Thiazolidinediones; Triazoles

Topics: Aged; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Substitution; Drug Therapy, Combination; Glyburide; Humans; Hypoglycemia; Hypoglycemic Agents; Kidney Failure, Chronic; Kidney Function Tests; Male; Metformin; Pyrazines; Sitagliptin Phosphate; Triazoles

There has been concern as to whether dipeptidyl peptidase-4 (DPP-4) inhibitors can be used safely in patients with relatively good glycemic control. This study, approved by the institutional review board of Hanzoumon Diabetes City Atlas Clinic, examined whether DPP-4 inhibitor sitagliptin could safely achieve good glycemic control without severe hypoglycemia by employing the "added food" concept. The subjects were 60 patients (46 men and 14 women) with type 2 diabetes who started sitagliptin therapy during a 1-month period from December 15, 2009 to January 15, 2010. They were recommended to have added food between meals to prevent hypoglycemia, while maintaining the same daily calorie intake. HbA(1c) decreased from 7.1 ± 1.2% to 6.5 ± 0.6% after 6 months of sitagliptin treatment (p < 0.001). In patients with a baseline HbA(1c) <7%, it decreased from 6.5 ± 0.3% to 6.1 ± 0.4% (p < 0.001). Systolic blood pressure was significantly reduced from 127.7 ± 17.0 to 122.7 ± 17.9 mmHg in the patients with a baseline HbA(1c) < 7% (p = 0.018). However, body weight increased by approximately 900 g and high-density lipoprotein cholesterol decreased significantly from 1.57 ± 0.46 to 1.43 ± 0.35 mmol/L (p < 0.01) in the patients concomitantly receiving sulfonylureas with sitagliptin. Excellent glycemic control was achieved by sitagliptin treatment together with the added food concept. However, combined use of sitagliptin with sulfonylureas requires attention to weight gain and the lipid profile. Further clinical studies will elucidate whether sitagliptin can decrease cardiovascular events as well as normalizing blood glucose and lowering the blood pressure.

Topics: Aged; Blood Glucose; Blood Pressure; Cholesterol, HDL; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Eating; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Lipids; Male; Middle Aged; Pyrazines; Severity of Illness Index; Sitagliptin Phosphate; Sulfonylurea Compounds; Treatment Outcome; Triazoles; Weight Gain

In a previously-published study, adding sitagliptin or glipizide to ongoing metformin therapy provided similar HbA(1c) improvement (both groups, -0.7%) after 52 weeks in patients with type 2 diabetes (T2DM). Significantly fewer patients experienced symptomatic hypoglycemia with sitagliptin (5% of 588 patients) compared to glipizide (32% of 584 patients). Glycemic efficacy and patient characteristics may influence hypoglycemic events. The present analysis evaluated the risk of hypoglycemia with sitagliptin or glipizide after adjusting for the most recently measured HbA(1c) value.. Data for this analysis were from the aforementioned 52-week, randomized, double-blind, active-controlled study. The primary endpoint was confirmed hypoglycemia (i.e., symptomatic hypoglycemia confirmed with a concurrent fingerstick glucose ≤70 mg/dL [3.9 mmol/L]); the secondary endpoint was severe hypoglycemia (requiring medical or non-medical assistance or symptoms of neuroglycopenia). Complementary log-log regression random effects models with terms for treatment, most recently measured HbA(1c) value, time (i.e., days since randomization), gender, and age (< or ≥65 years) were used to assess adjusted subject-specific treatment effects.. Over the full range of HbA(1c) levels and follow-up time, the risk of confirmed hypoglycemic events was lower with sitagliptin compared with glipizide (31 vs. 448 events; adjusted hazard ratio [HR] = 0.05 [95% CI: 0.03, 0.09], p < 0.001). The risk was also lower with sitagliptin in the younger (HR = 0.06 [95% CI: 0.03, 0.12], p < 0.001) and older (HR = 0.02 [0.01, 0.08], p < 0.001) age groups compared with glipizide. For severe hypoglycemia events (2 vs. 22), the risk was lower with sitagliptin (HR = 0.08 [95% CI: 0.01, 0.47]; p = 0.005).. The actual time between the HbA(1c) measurement and the hypoglycemic event was variable and not controlled for in the analysis.. In pre-specified analyses adjusting for the most recently measured HbA(1c) value, there was a substantial reduction in risk for confirmed hypoglycemia with sitagliptin compared to glipizide when added to ongoing metformin therapy in patients with T2DM. The risk of confirmed hypoglycemia was very low in younger and older patients treated with sitagliptin.

Topics: Adult; Aged; Aged, 80 and over; Calibration; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glipizide; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Middle Aged; Multicenter Studies as Topic; Pyrazines; Randomized Controlled Trials as Topic; Risk Factors; Sitagliptin Phosphate; Time Factors; Triazoles

We evaluated the association between self-monitoring of blood glucose (SMBG) use and sitagliptin or sitagliptin/metformin (SSMT) adherence. SSMT was chosen as these medications have little risk of hypoglycemia and are believed to not require SMBG data for titration.. This was an observational study using data extracted from a large United States insurance claims database (i3 InVision™ Data Mart, Ingenix, Inc.). Data were extracted on noninsulin-using patients initiating SSMT for each 12-month period pre- and post-SSMT initiation. Logistic regression was used to assess the relationship between SMBG use and the likelihood of being medication adherent (defined as a medication possession ratio of ≥75%) while controlling for covariates.. This analysis included 7,306 patients (57.6% male; mean age 54.2 years). Mean pre-SSMT hemoglobin A1c (HbA1c) was 8.0%. In the post-SSMT initiation period, 58% of patients were adherent with SSMT. Older age, male gender, prior use of oral diabetes medication, and lower HbA1c were associated with improved SSMT adherence. SMBG use was associated with improved adherence [odds ratio (OR) ranged from 1.198 to 1.338; p < .05] compared with patients with no SMBG use pre- or post-SSMT initiation. For patients who began SMBG after starting SSMT, greater SMBG use was associated with better adherence (OR 1.449 for higher vs 1.246 for lower strip use; p < .05).. This study demonstrated that SMBG is associated with improved SSMT adherence. This relationship is strengthened with greater SMBG use.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Child; Computer Simulation; Diabetes Mellitus; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Logistic Models; Male; Medication Adherence; Metformin; Middle Aged; Odds Ratio; Predictive Value of Tests; Pyrazines; Risk Factors; Sitagliptin Phosphate; Time Factors; Treatment Outcome; Triazoles; United States; Young Adult

Sitagliptin, the first of a new class of dipeptidyl peptidase-4 (DPP-4)-inhibitory oral antihyperglycemic drugs (OHDs), was introduced in Japan in December 2009. In April 2010 a safety alert was issued regarding the risk of serious hypoglycemic events when the drug is used in combination with high-dose sulfonylureas (SUs).. To investigate trends in prescription of OHDs before and after the launch of sitagliptin, and before and after the safety alert, in order to evaluate changes in the prescribing behavior of various groups of physicians in response to the safety alert.. Japan.. Prescription data from 6,500 institutions, randomly collected from 300 Japanese pharmacies were used. A cohort of 87,678 patients with 813,374 prescriptions for OHDs, among which 464,079 included SUs (glimepiride: 317,423), was collected from August 2009 to 31 December 2010. Logistic regression analysis was conducted.. Prescription trends for sitagliptin and SUs, stratified by age, gender, types of prescribers and institutions.. The safety alert recommending a reduction of SU dosing was well reflected in prescriptions issued after the alert (glimepiride dose reduction from 2.78 ± 1.86 mg to 2.32 ± 1.68), especially in prescriptions issued by diabetes specialists (from 2.27 ± 1.81 mg to 1.87 ± 1.47 mg). The dose of background SUs in patients who started sitagliptin early was higher (before alert: 2.70 ± 1.80 mg, after alert: 2.51 ± 1.74 mg) than in patients without experience of sitagliptin (2.12 ± 1.57 mg). This may indicate that patients receiving high-dose SUs were selected for sitagliptin, and this might be a factor in the high frequency of hypoglycemia in the early launch phase of sitagliptin.. The sitagliptin safety alert had a clear impact on prescribing behavior, but the impact appeared to depend on prescribers' backgrounds. Our findings should be helpful for developing a safer drug launching strategy for new classes of drugs in established categories.

Topics: Administration, Oral; Adverse Drug Reaction Reporting Systems; Aged; Chi-Square Distribution; Dipeptidyl-Peptidase IV Inhibitors; Drug Prescriptions; Drug Utilization; Drug Utilization Review; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Japan; Logistic Models; Male; Middle Aged; Patient Safety; Practice Patterns, Physicians'; Pyrazines; Retrospective Studies; Sitagliptin Phosphate; Sulfonylurea Compounds; Time Factors; Triazoles

this study reports on the effectiveness of sitagliptin in Asian Indian type 2 diabetes patients seen at a tertiary diabetes care center who had inadequate glycemic control with oral hypoglycemic agents either alone or in combination, compared to a group of patients who received insulin glargine.. patients with type 2 diabetes mellitus (n = 2,817) whose glycemia was not controlled adequately (glycated hemoglobin >6.5%) with oral hypoglycemic agents (either alone or in combination) received oral sitagliptin 100 mg once daily in addition to existing therapy for a period of 24 weeks. Patients who received insulin glargine as add-on therapy (n = 2,743) served as the reference group. Data analysis included glycated hemoglobin, fasting plasma glucose, lipid profile, body weight, and the occurrence of hypoglycemia.. significant reductions in glycated hemoglobin and fasting plasma glucose values were noted after 24 weeks of additional sitagliptin therapy that were comparable to those with insulin glargine. While sitagliptin addition resulted in a small weight loss (0.3 kg), insulin glargine addition resulted in a weight gain (0.7 kg). The overall incidence of adverse experiences was low and generally mild in both groups.. in a large group of Asian Indian type 2 diabetes patients seen at a tertiary diabetes center in whom glycemia was not controlled adequately by oral hypoglycemic agents (either alone or in combination), addition of sitagliptin helped to achieve glycemic control to a similar extent as insulin glargine but with a marginal weight advantage.

Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glycated Hemoglobin; Humans; Hypoglycemia; India; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Pyrazines; Retrospective Studies; Sitagliptin Phosphate; Statistics, Nonparametric; Triazoles; Triglycerides

In the context of a need for improved strategies to control glycemia in patients with type 2 diabetes, new information was discussed during the American Diabetes Association's annual meeting on the dipeptidyl peptidase 4 inhibitor sitagliptin. As reviewed below, clinical trials corroborated the feasibility of adding sitagliptin to ongoing metformin or pioglitazone therapy, without the risk for hypoglycemia or the negative impact on body weight observed after add-on sulfonylureas, although the neutral or beneficial effect of sitagliptin on body weight resulted from a complex interaction with baseline levels of hemoglobin A1c levels and the change brought about by treatment. New studies of sitagliptin presented during the meeting also indicated additional effects of the drug not mediated by inhibition of dipeptidyl peptidase-4, but through direct inhibition of endogenous glucose production and/or glucagon responses and improved β-cell glucose sensitivity.

Topics: Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Pyrazines; Sitagliptin Phosphate; Triazoles

The overall safety profiles of GLP-1 agonists and DPP-4 inhibitors are favorable, with a low incidence of hypoglycemia. This attribute, along with their weight and cardiovascular benefits, particularly with the GLP-1 agonists, make them appropriate choices in our 3 patient cases. Ongoing safety investigations with GLP-1 agonists and DPP-4 inhibitors will provide further clarity to the complete safety profiles of these agents.

Topics: Adamantane; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Exenatide; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incretins; Insulin; Liraglutide; Male; Metformin; Middle Aged; Peptides; Pyrazines; Receptors, Glucagon; Risk; Sitagliptin Phosphate; Triazoles; Venoms; Weight Loss

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Pyrazines; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Triazoles

Topics: Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Metformin; Peptides; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Venoms; Weight Loss

Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Metformin; Pyrazines; Reference Values; Sitagliptin Phosphate; Triazoles