Efficacy and Safety of Adding Sitagliptin in Type 2 Diabetes Patients on Insulin: Age-Stratified Comparison at One Year in the ASSIST-K Study.

BACKGROUND: Sitagliptin, the first dipeptidyl peptidase-4 inhibitor, has demonstrated efficacy and safety as monotherapy and as add-on therapy to oral antidiabetic agents or insulin. However, there have been few reports about sitagliptin in elderly patients. The ASSIST-K observational study was performed in patients with type 2 diabetes mellitus (T2DM) receiving sitagliptin as add-on therapy to insulin. Changes of hemoglobin A1c (HbA1c), body weight, and the estimated glomerular filtration rate (eGFR), as well as adverse events, were investigated over 12 months in age-stratified groups. METHODS: Among outpatients with T2DM treated at member institutions of Kanagawa Physicians Association, those starting sitagliptin as add-on therapy to insulin were followed for 12 months. HbA1c (National Glycohemoglobin Standardization Program), body weight, and eGFR were the efficacy endpoints, while adverse events were investigated to assess safety. Patients were stratified into three age groups (≤ 64 years, 65 - 74 years, and ≥ 75 years) for comparison of the endpoints. RESULTS: Among 937 patients on insulin before starting sitagliptin, 821 patients were analyzed after excluding those without HbA1c data at baseline and 12 months. The two groups of elderly patients (65 - 74 years and ≥75 years) had more complications and their HbA1c was lower at initiation of sitagliptin therapy. The dose of sitagliptin, daily number of insulin injections, and number of concomitant oral antidiabetic agents were all lower in the elderly patients. HbA1c showed a significant decrease after initiation of sitagliptin in all age groups, and there were no significant intergroup differences in the change of HbA1c at 12 months. Body weight did not change significantly in any group. eGFR decreased significantly in all groups, with no significant intergroup differences at 12 months. Regarding adverse events, there were no significant intergroup differences in the incidence of severe hypoglycemia, gastrointestinal symptoms, or constipation. CONCLUSIONS: Despite baseline differences in demographic factors and medications, sitagliptin showed good efficacy and safety in all age groups of patients receiving it as add-on therapy to insulin during routine management of T2DM. Adding sitagliptin to insulin achieves similar efficacy and safety outcomes at 12 months in both elderly and non-elderly T2DM patients.

Relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetic patients (JDDM38).

AIMS/INTRODUCTION: We carried out an observational cohort study to examine the relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetics. MATERIALS AND METHODS: We analyzed the CoDiC(®) database of the Japan Diabetes Data Management Study Group across 67 institutions in Japan. In a total of 3,698 drug-naïve patients who were initiated with metformin, dipeptidyl peptidase-4 inhibitor (DPP-4i) or sulfonylurea (SU) from 2007 to 2012, we evaluated body mass index (BMI) and hemoglobin A1c (HbA1c). The patients were stratified according to their clinical features, and matched using a propensity score to adjust for baseline factors. RESULTS: HbA1c was reduced with all drugs, with the largest effect elicited by DPP-4i and the smallest by SU (P = 0.00). HbA1c increased with SU after 6 months in the patients stratified by an age-of-onset of <50 years (P = 0.00). BMI increased with SU in the patients stratified by a BMI of <25 (P = 0.00), and decreased with metformin in the patients with a BMI >25 (P = 0.00). The reduction in HbA1c was larger in patients with HbA1c of ≥8%, compared with that in patients with HbA1c of <8% (P = 0.00). HbA1c during the study period was higher in patients who were added to or swapped with other drug(s), than in patients continued on the original drug (P = 0.00). CONCLUSIONS: The effect on bodyweight and glycemic control differed among metformin, DPP-4i and SU, and the difference was associated with clinical features.

Factors Predicting Therapeutic Efficacy of Combination Treatment With Sitagliptin and Insulin in Type 2 Diabetic Patients: The ASSIST-K Study.

BACKGROUND: It is unclear whether dipeptidyl peptidase-4 inhibitors decrease hemoglobin A1c (HbA1c) in a glucose-dependent manner in patients on insulin therapy who have impaired insulin secretion. This study investigated factors influencing the efficacy of sitagliptin when used concomitantly with insulin to treat type 2 diabetes mellitus (T2DM) in the real-world setting. METHODS: A retrospective study was conducted of 1,004 T2DM patients at 36 Japanese clinics associated with the Diabetes Task Force of the Kanagawa Physicians Association. Eligible patients had been on insulin for at least 6 months, with a baseline HbA1c of 7.0% (53 mmol/mol) or higher. Baseline characteristics and laboratory data from 495 patients were subjected to multiple regression analysis to identify factors influencing the change of HbA1c. RESULTS: Most patients (n = 809) received sitagliptin at a dose of 50 mg. In the 1,004 patients, HbA1c decreased by 0.74% (6 mmol/mol) and body weight increased by 0.1 kg after 6 months of combination therapy. Multiple regression analysis showed that a higher baseline HbA1c, older age, and lower body mass index influenced the change of HbA1c after 6 months. Hypoglycemic symptoms occurred in 7.4%, but none were severe. CONCLUSIONS: These results emphasize the importance of a higher HbA1c at the commencement of sitagliptin therapy in patients on insulin. Glucose-dependent suppression of glucagon secretion by sitagliptin may be useful in patients with impaired insulin secretion. Sitagliptin can be used concomitantly with insulin irrespective of the insulin regimen, duration of insulin treatment, and concomitant medications.

Two-year assessment of the efficacy and safety of sitagliptin in elderly patients with type 2 diabetes: Post hoc analysis of the ASSET-K study.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Safety and efficacy of adding sitagliptin to insulin in patients with type 2 diabetes: the ASSIST-K study.

We retrospectively studied more than 1000 patients with type 2 diabetes attending 36 Japanese clinics to investigate the efficacy and safety of adding sitagliptin to various insulin regimens. We found that the treatment with add-on sitagliptin for 6-months was effective, irrespective of the type or dose of concomitant insulin.

Pleiotropic effects of sitagliptin in the treatment of type 2 diabetes mellitus patients.

BACKGROUND: Sitagliptin is a DPP-4 inhibitor that became available for use in Japan three years ago. This study was conducted to identify the pleiotropic effects of sitagliptin other than blood glucose lowering in Japanese type 2 diabetes mellitus patients. METHODS: A retrospective, observational study of 940 type 2 diabetes mellitus patients was conducted. The primary outcome measures were HbA1c, blood pressure, and lipid profiles measured at 0, 4, and 12 weeks of sitagliptin therapy. RESULTS: After 12 weeks of sitagliptin treatment, compared with baseline, HbA1c decreased 0.64% ± 0.86%; systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly; and serum creatinine (Cr) and uric acid (UA) levels were mildly but significantly elevated. A correlation analysis of the changes in systolic blood pressure, diastolic blood pressure, creatinine, and uric acid (ΔSBP, ΔDBP, ΔCr, ΔUA) from baseline to 12 weeks showed significant negative correlations between ΔSBP and ΔCr, ΔSBP and ΔUA, and ΔDBP and ΔCr. Total cholesterol and postprandial triglycerides were significantly decreased at both 4 and 12 weeks. Alkaline phosphatase (ALP) decreased significantly, and there was a significant positive correlation between changes in ALP and HbA1c. CONCLUSIONS: Sitagliptin seems to be effective not only in lowering blood glucose but also in lowering blood pressure, lipid, and ALP levels. Sitagliptin appears to contribute to a Na-diuretic action due to GLP-1.

Cross-sectional survey of diabetic neuropathy in Kanagawa and clinical significance of a touch test using tissue paper.

UNLABELLED: Aims/Introduction: The prevalence of diabetes mellitus is increasing rapidly in Japan, and diabetic neuropathy is a major factor decreasing diabetic patients' quality of life, as well as a risk factor for sudden death. The present study aimed to determine the prevalence of diabetic neuropathy and raise awareness about it among patients and their physicians. MATERIALS AND METHODS: Diabetic outpatients (N = 5077) at 249 medical institutions within Kanagawa Prefecture, Japan, were surveyed by questionnaire and underwent foot examinations. The questionnaire included 10 questions about sensory abnormalities of both feet, muscle cramps and autonomic symptoms. Foot examinations included testing for vibratory perception of the medial malleolus, Achilles tendon reflexes and touch sensation of the bottom of the great toe using tissue paper. RESULTS: Of the 5077 patients surveyed, 70.4% reported symptoms. Overall, 75.4% of the patients underwent vibratory perception testing, of whom 44.9% had abnormal thresholds (≤10 s). On the tissue paper touch test, performed in 94.6% of patients, 11.9% had no touch sensation. Of the 2803 type 2 diabetic patients with known background factors who underwent foot examinations, 49.4% had diabetic neuropathy. There was a high prevalence of diabetic neuropathy (36.1%) in patients with <5-year history. Of the patients with no touch sensation on the tissue paper test, 81.3% had diabetic neuropathy. CONCLUSIONS: The present study identified the prevalence of diabetic neuropathy in Kanagawa Prefecture. The tissue paper test is a simple and excellent method of evaluating decreased superficial sensation that can help evaluate the severity of diabetic neuropathy. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00174.x, 2011).

Present status of insulin therapy for type 2 diabetes treated by general practitioners and diabetes specialists in Japan: Third report of a cross-sectional survey of 15,652 patients.

UNLABELLED: Aims/Introduction: Insulin therapy is often required to achieve good glycemic control in patients with type 2 diabetes mellitus. However, some providers, particularly general practitioners (GPs), are reluctant to prescribe insulin to their patients. The aim of the present study was to clarify any differences in, as well as any problems associated with, insulin therapy in patients with type 2 diabetes being treated by either a GP or a diabetes specialist in Japan. MATERIALS AND METHODS: Of 15,652 patients across 721 clinics and hospitals, 15,350 were diagnosed with type 2 diabetes (14,312 by GPs and 1038 by specialists). Data regarding glycated hemoglobin (HbA1c) levels, age, height, bodyweight and treatment modality were collected for each patient. RESULTS:   Of the patients with type 2 diabetes, 9.1 and 22.9% had been prescribed insulin monotherapy, and 38.8 and 37.0% were also receiving insulin with an oral antidiabetic (OAD) by GPs or specialists, respectively. Diabetes specialists prescribed analog insulin more frequently than did GPs. GPs chose premixed insulin more frequently than did specialists, and this factor correlated with higher HbA1c levels. A younger age and daily insulin dose in groups being treated by both providers were correlated with high HbA1c levels on insulin monotherapy. Neither type of insulin nor OAD was correlated with HbA1c on insulin plus OAD therapy. CONCLUSIONS:   To achieve better glycemic control with insulin therapy, sufficient insulin dose and intensive treatment regimen, in addition to lifestyle interventions, might be necessary. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00198.x, 2012).

Efficacy and safety of sitagliptin monotherapy and combination therapy in Japanese type 2 diabetes patients.

UNLABELLED: (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00221.x, 2012) Aims/Introduction: To determine the efficacy and safety of sitagliptin monotherapy and combination therapy in Japanese type 2 diabetes patients after 3 months' therapy. MATERIALS AND METHODS: A retrospective, observational study of 741 type 2 diabetes patients was carried out; 110 received sitagliptin monotherapy, and 631 received combination therapy with sitagliptin when other oral medications were insufficient. The primary outcome measure was glycated hemoglobin (HbA1c) measured at 0, 4 and 12 weeks of sitagliptin therapy. RESULTS: In the monotherapy and combination therapy groups, HbA1c decreased significantly after 12 weeks. Target HbA1c (<7%) was achieved in 39.1% overall. On logistic regression analysis, baseline HbA1c was the strongest contributing factor for achieving target HbA1c; baseline body mass index and duration of diabetes were also significant factors. A total of 82 patients (11%) were unresponsive to sitagliptin. These patients' baseline body mass index was significantly higher and their baseline HbA1c was significantly lower than those of patients who responded to sitagliptin. The most commonly co-administered drugs were sulfonylureas (508 patients). In these patients, the dose of sulfonylurea decreased with time. In 66 patients whose sulfonylurea dosage was reduced when sitagliptin was started, HbA1c and bodyweight decreased significantly after 12 weeks. A total of 24 patients receiving sulfonylureas had mild hypoglycemia, but none discontinued sitagliptin. CONCLUSIONS: Sitagliptin was effective and safe as both monotherapy and combination therapy in Japanese type 2 diabetes patients. When sulfonylureas were ineffective, sitagliptin improved glycemic control. In patients whose sulfonylurea dose was reduced at the start of sitagliptin, blood glucose improved and bodyweight decreased after 12 weeks.

Present status of sulfonylurea treatment for type 2 diabetes in Japan: second report of a cross-sectional survey of 15,652 patients.

Sulfonylureas are commonly used for the treatment of patients with type 2 diabetes mellitus (T2DM). However, some clinical concerns regarding their use have grown over the past decade. Thus, results of a previous Japan-wide cross-sectional survey of patients with type 2 diabetes mellitus (T2DM) were analyzed to determine the present status and problems associated with the use of sulfonylureas in the treatment of T2DM by general practitioners (GPs) and diabetes specialists. Of 15,652 patients across 721 clinics and hospitals from the previous survey, 15,350 were diagnosed as T2DM (14,312 by GPs and 1,038 by specialists). For each patient, data were collected for HbA1c levels, age, height, body weight, and treatment modality. Of T2DM patients being treated by GPs, 35.4% and 60.0% received sulfonylureas in entire oral drugs or as monotherapy, respectively, compared with 29.2% and 61.2% of patients, respectively, treated by specialists. Of the patients treated with sulfonylurea monotherapy, 1335 patients (35.2%) achieved HbA1c <6.5%, whereas HbA1c was >or=8.0% in 531 patients (14.0%). Patients with HbA1c levels >or=8.0% had a higher body mass index, used glibenclamide more frequently, and used higher doses of sulfonylureas than patients in whom HbA1c levels were <6.5%. In conclusion, the present study shows that sulfonylureas are central in the treatment of T2DM in Japan. However, careful consideration of suitable patients, agents, and doses is necessary to achieve appropriate glycemic control.

The status of glycemic control by general practitioners and specialists for diabetes in Japan: a cross-sectional survey of 15,652 patients with diabetes mellitus.

To determine the status of diabetes care by general practitioners and diabetes specialists in Japan, we conducted a nation-wide cross-sectional survey. We asked 8112 clinics and hospitals randomly, from throughout Japan, to participate in this study and 721 facilities agreed. A total of 15,652 patients aged from 15 to 97 with type 1 and type 2 diabetes were enrolled. Of these, 14,560 (93.0%) and 1092 (7.0%) patients were cared for by general practitioners and diabetes specialists, respectively. HbA1c levels were measured by a latex agglutination method, and age, height, body weight, type of diabetes and treatment modality were obtained from each patient. Mean HbA1c level for all patients treated by general practitioners was significantly lower than for those treated by the diabetes specialists (6.8+/-1.2% vs. 7.0+/-1.2%, p=0.0002). Mean HbA1c level for patients without insulin therapy was lower than for those treated with insulin, irrespective of caring physician. The proportion of patients treated with insulin therapy by diabetes specialists was higher (17.7%) than that by general practitioners (6.5%). This study showed that average HbA1c levels in Japanese patients treated by either general practitioners or specialists was acceptable, regardless of study limitations or bias.