Pretreatment body mass index affects achievement of target blood pressure with sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus and chronic kidney disease.

Sodium-glucose cotransporter 2 inhibitor (SGLT2-I) shows excellent antihypertensive effects in addition to its hypoglycemic effects. However, whether body mass index (BMI) affects the antihypertensive effect of SGLT2-I remains unknown. We investigated the impact of baseline BMI on the achievement of target blood pressure (BP) with SGLT2-I treatment in Japanese patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). We retrospectively evaluated 447 Japanese patients with T2DM and CKD treated with SGLT2-I for at least 1 year. The primary outcome was achieving the target BP (<130/80 mmHg) after SGLT2-I treatment. Patients were divided into two groups according to a baseline BMI of 29.1 determined by receiver operating characteristic analysis and analyzed in a cohort model with propensity score matching. In each group, 130 patients were compared by propensity score matching. The target BP achievement rate was significantly higher in the BMI < 29.1 group than in the BMI ≥ 29.1 group (34% and 21%, respectively, p = 0.03). The odds ratio for achieving the target BP in the BMI ≥ 29.1 group was 0.50 (95% confidence interval, 0.28-0.90, p = 0.02). The BMI < 29.1 group had significantly lower systolic and diastolic BPs after SGLT2-I treatment than the BMI ≥ 29.1 group. Only the BMI < 29.1 group was showed a significant decrease in the logarithmic albumin-to-creatinine ratio from baseline after SGLT2-I treatment. In patients with T2DM and CKD, baseline BMI was associated with the antihypertensive effects of SGLT2-I. Patients in the lower baseline BMI group were more likely to achieve the target BP after SGLT2-I treatment. Pretreatment BMI affects the antihypertensice effect of SGLT2 inhibirors in patients with T2DM and CKD.

Comparison of renal outcomes between sodium glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists.

AIMS: This study aimed to clarify the differences in how sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1Ra) influence kidney function in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: We retrospectively built two databases of patients with T2DM who visited the clinics of members of Kanagawa Physicians Association. We defined the renal composite outcome as either progression of albuminuria status and/or > 15% deterioration in estimated glomerular filtration rate (eGFR) per year. We used propensity score matching to compare patient outcomes after SGLT2i and GLP1Ra treatments. RESULTS: The incidence of renal composite outcomes was significantly lower in SGLT2i-treated patients than in GLP1Ra-treated patients (n = 15[11%] and n = 27[20%], respectively, P = 0.001). Annual eGFR changes (mL/min/1.73 m2/year) between the two groups differed significantly (-1.8 [95 %CI, -2.7, -0.9] in SGLT2i-treated patients and - 3.4 [95 %CI, -4.6, -2.2] in GLP1Ra-treated patients, P = 0.0049). The urine albumin-to-creatinine ratio changed owing to a significant interaction between the presence or absence of a decrease in systolic blood pressure and the difference in treatments (P < 0.04). CONCLUSION: Renal composite outcome incidence was lower in SGLT2i-treated patients than in GLP1Ra-treated patients.

Retrospective Analysis of the Renoprotective Effects of Long-Term Use of Six Types of Sodium-Glucose Cotransporter 2 Inhibitors in Japanese Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease.

Aim: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) provide renal protection in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to elucidate the renal effects of long-term use of six types of SGLT2is in Japanese patients with T2DM and chronic kidney disease (CKD). Materials and Methods: The Kanagawa Physicians Association maintains a registry of patients who visit their 31 clinics. We retrieved clinical data of patients with T2DM and CKD who were prescribed with SGLT2is for >1 year. Results: A total of 763 patients with a median treatment duration of 33 months were included. The logarithmic value of urine albumin-creatinine ratio (LNACR) decreased significantly from 1.60 ± 0.65 to 1.51 ± 0.67. The multiple linear regression analysis revealed that the LNACR at the initiation of treatment, change in (Δ) diastolic blood pressure, and Δ hemoglobin A1c were independently correlated with ΔLNACR (P < 0.001). The decrease in the LNACR was significantly smaller in the patients with estimated glomerular filtration rate (eGFR) [mL/(min ·1.73 m2)] of <60 (P < 0.05). The eGFR decreased from 77.4 ± 22.3 to 72.7 ± 22.5 mL/(min ·1.73 m2) (P < 0.001). The multiple linear regression analysis showed that the LNACR at the initiation of treatment, Δbody weight at the previous survey, ΔeGFR at the previous survey, and the eGFR at the initiation of treatment correlated independently with ΔeGFR during the maintenance period (P < 0.001). Greater changes in the eGFR during the maintenance period were observed in the patients with macroalbuminuria or eGFR of <60 (P < 0.01). Conclusions: The study confirmed that the long-term use of six types of SGLT2i improved the albumin-creatinine ratio (ACR), although the eGFR gradually decreased during the treatment. The change in the ACR was significantly smaller in the patients with eGFR of <60 mL/(min ·1.73 m2) than in those with eGFR of >60 mL/(min ·1.73 m2). However, this was a retrospective observational study; further studies are needed to formulate final conclusions.

Blood pressure after treatment with sodium-glucose cotransporter 2 inhibitors influences renal composite outcome: Analysis using propensity score-matched models.

AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcome in patients with type 2 diabetes mellitus, but the mechanism is not fully understood. The aim of this retrospective study was to assess the association of achieved blood pressure with renal outcomes in Japanese type 2 diabetes mellitus patients with chronic kidney disease. MATERIALS AND METHODS: We assessed 624 Japanese type 2 diabetes mellitus patients with chronic kidney disease taking SGLT2i for >1 year. The patients were classified as those with post-treatment mean arterial pressure (MAP) of ≥92 mmHg (n = 344) and those with MAP of <92 mmHg (n = 280) for propensity score matching (1:1 nearest neighbor match with 0.04 of caliper value and no replacement). The end-point was a composite of progression of albuminuria or a decrease in the estimated glomerular filtration rate by ≥15% per year. RESULTS: By propensity score matching, a matched cohort model was constructed, including 201 patients in each group. The incidence of renal composite outcome was significantly lower among patients with MAP of <92 mmHg than among patients with MAP of ≥92 mmHg (n = 11 [6%] vs n = 26 [13%], respectively, P = 0.001). The change in estimated glomerular filtration rate was similar in the two groups; however, the change in the albumin-to-creatinine ratio was significantly larger in patients with MAP of <92 mmHg. CONCLUSIONS: In Japanese type 2 diabetes mellitus patients with chronic kidney disease, blood pressure after SGLT2i administration influences the renal composite outcome. Blood pressure management is important, even during treatment with SGLT2i.

A Study of Seasonal Variation in the Effect of Add-On Sitagliptin on Blood Glucose Control in Insulin-Treated Patients With Type 2 Diabetes.

BACKGROUND: There are several reports of seasonal variation in hemoglobin A1c (HbA1c) in patients with type 2 diabetes (T2DM), but no reports of seasonal variation in the effect of add-on drugs on blood glucose control in insulin-treated patients. METHODS: Using data collected from 630 patients in a multicenter study, we compared the amount of change in HbA1c after 1, 3, 6, 9, and 12 months of add-on administration of sitagliptin in insulin-treated patients divided into four groups based on the month when sitagliptin was started. RESULTS: A significantly larger decrease in HbA1c at 6 months from baseline was observed in the group that started add-on sitagliptin in February to April than in the other three groups. However, the amount of change in HbA1c at 12 months did not differ among the groups. CONCLUSIONS: The consideration of seasonal variation enables more accurate evaluation of a drug's short-term effect on blood glucose control.

The effect of long-term past glycemic control on executive function among patients with type 2 diabetes mellitus.

OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) show more executive dysfunction than nondiabetics. However, how long poor glycemic control affects executive function remains unclear. Thus, we aimed to investigate the relationships in a cross-sectional study. METHODS: We studied 118 T2DM outpatients (age, ≥ 60 years; excluding history of stroke, dementia and severe hypoglycemia). HbA1c values were recorded every ≤ 12 weeks for ≥ 5 years. All patients underwent verbal-fluency tests (reflecting executive function) and Mini-Mental State Examination (MMSE). The correlation between past glycemic control values and both cognitive tests scores was investigated. As markers of past glycemic control, we used average hemoglobin A1c (HbA1c) values and glycemic control variability [coefficient of variation (CV) of HbA1c values (HbA1c-CV)]. RESULTS: Verbal-fluency tests scores correlated with HbA1c-CV, but not with average HbA1c values, after adjusting for age, years of education and sex. Verbal-fluency tests scores correlated with HbA1c-CV for the past 5 years, best compared with HbA1c-CV for past < 5 years. MMSE scores were also related to only HbA1c-CV for the past 3 years in an adjustment model. CONCLUSIONS: Five-year HbA1c variability affected executive function in T2DM patients, but not average HbA1c values. Long-term longitudinal studies may be required.

Effects of ipragliflozin on the development and progression of kidney disease in patients with type 2 diabetes: An analysis from a multicenter prospective intervention study.

AIMS/INTRODUCTION: Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. METHODS: This was an investigator-initiated multicenter prospective intervention study in which ipragliflozin (50 mg) was administered once daily, and glycemic control, estimated glomerular filtration rate (eGFR) and adverse events were evaluated until 104 weeks after starting research. RESULTS: There were 407 patients analyzed. In the eGFR ≥90 group and eGFR ≥60 to <90 group, eGFR had significantly decreased compared with baseline at all time points from 4 to 104 weeks. There were significant increases in the eGFR ≥45 to <60 groups compared with baseline at 36 weeks (2.3 ± 1.0) and 52 weeks (2.6 ± 1.2). Comparison between the eGFR <60, urine albumin-to-creatinine ratio >300 group and the eGFR <60, urine albumin-to-creatinine ratio <300 group showed a greater reduction in eGFR in the former (-5.4 ± 2.4 vs 3.3 ± 1.1) at 12 weeks and was maintained to 104 weeks. In any group, eGFR did not significantly decrease until 104 weeks compared with 4 weeks. The urine albumin-to-creatinine ratio after 52 weeks and after 104 weeks was significantly decreased compared with baseline in the eGFR ≥90 group. CONCLUSIONS: Ipragliflozin lowers eGFR and corrects hyperfiltration in patients with high eGFR (eGFR ≥60). In patients with low eGFR (eGFR ≥30 to <60), ipragliflozin has the possibility of increasing eGFR and exerting a renoprotective effect.

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.

Association of usual sleep quality and glycemic control in type 2 diabetes in Japanese: A cross sectional study. Sleep and Food Registry in Kanagawa (SOREKA).

OBJECTIVES: Excessively short and long sleep durations are associated with type 2 diabetes, but there is limited information about the association between sleep quality and diabetes. Accordingly, the present study was performed to investigate this relationship. MATERIALS AND METHODS: The subjects were 3249 patients with type 2 diabetes aged 20 years or older. Sleep quality was assessed by using the Pittsburgh Sleep Quality Index (PSQI). A higher global PSQI score indicates worse sleep quality, and a global PSQI score >5 differentiates poor sleepers from good sleepers. RESULTS: The mean global PSQI score was 5.94 ± 3.33, and 47.6% of the patients had a score of 6 or higher. Regarding the components of the PSQI, the score was highest for sleep duration, followed by subjective sleep quality and then sleep latency in decreasing order. When the patients were assigned to HbA1c quartiles (≤ 6.5%, 6.6-7.0%, 7.1-7.8%, and ≥ 7.9%), the top quartile had a significantly higher global PSQI score than the other quartiles. The top HbA1c quartile had a sleep duration of only 6.23 ± 1.42 hours, which was significantly shorter than in the other quartiles. Also, sleep latency was 25.3 ± 31.8 minutes in the top quartile, which was significantly longer (by approximately 20 minutes) than in the other quartiles. When analysis was performed with adjustment for age, gender, BMI, smoking, and other confounders, the global PSQI score was still significantly higher and sleep duration was shorter in the top HbA1c quartile (HbA1c ≥ 7.9%). CONCLUSIONS: Japanese patients with type 2 diabetes were found to have poor subjective sleep quality independently of potential confounders, especially those with inadequate glycemic control. Impairment of sleep quality was associated with both increased sleep latency and a shorter duration of sleep.

Effectiveness of Ipragliflozin for Reducing Hemoglobin A1c in Patients With a Shorter Type 2 Diabetes Duration: Interim Report of the ASSIGN-K Study.

BACKGROUND: Ipragliflozin is a selective sodium glucose co-transporter 2 inhibitor. The ASSIGN-K study is investigating the efficacy and safety of ipragliflozin for type 2 diabetes mellitus (T2DM) in the real-world clinical setting. METHODS: Japanese T2DM patients with inadequate glycemic control despite diet and exercise with/without pharmacotherapy were enrolled in an investigator-driven, multicenter, prospective, observational study examining the efficacy and safety of ipragliflozin treatment (50 mg/day for 52 weeks). We performed interim analysis after 24 weeks. RESULTS: In 367 patients completing 24-week ipragliflozin therapy, hemoglobin A1c (HbA1c) decreased significantly from 8.07% at baseline to 7.26% in week 24 (P < 0.001). The change in HbA1c from treatment initiation to week 24 was -0.88% in patients < 65 years old versus -0.55% in those ≥ 65 years and -0.92% in men versus -0.70% in women (all P < 0.001). When baseline HbA1c was < 7%, 7% to < 8%, and ≥ 8%, the change was -0.18%, -0.45%, and -1.48%, respectively (P = 0.5352, P < 0.001, and P < 0.001, respectively). When baseline body mass index (BMI) was < 25, 25 to < 30, and ≥ 30, the change was -1.05%, -0.65%, and -0.87%, respectively (all P < 0.001). Multiple regression analysis showed that HbA1c decreased more in patients with a higher baseline HbA1c or shorter duration of diabetes. An HbA1c < 7% was achieved in 33.3% of the patients, and their baseline HbA1c was significantly lower than that of patients failing to achieve it (P < 0.001). Adverse events (AEs) occurred in 106/451 patients (23.5%), including 29.1% of patients aged 65 or older. Common AEs were vulvovaginal candidiasis (3.1%) and genital pruritus (1.8%). Serious AEs included urinary tract infection, unstable angina, and ketosis, which occurred in patients who did not suspend medication during acute illness. CONCLUSIONS: Ipragliflozin significantly improved HbA1c in T2DM patients with inadequate glycemic control. Improvement in HbA1c was significant irrespective of age, sex, baseline HbA1c, or BMI, but efficacy was greater with a higher baseline HbA1c and shorter duration of diabetes. For safe continuation of treatment, patients should be advised to suspend medication during acute illness.

Ipragliflozin Improves Glycemic Control and Decreases Body Fat in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Ipragliflozin, a sodium-glucose transporter 2 inhibitor, was administered to patients with type 2 diabetes mellitus for 24 weeks to evaluate its effect on glycemic control and body composition. METHODS: This was an investigator-initiated multicenter prospective intervention study in which ipragliflozin (50 mg) was administered once daily and glycemic control, blood pressure, body weight (BW), body composition (measured by a biological impedance method), the lipid profile, and adverse events were evaluated after 4, 12, and 24 weeks of treatment. RESULTS: Efficacy and safety up to 24 weeks of ipragliflozin therapy were analyzed in 367 patients and 451 patients, respectively. Hemoglobin A1c decreased significantly from 8.07% at the start of ipragliflozin therapy to 7.26% in week 24 (P < 0.001). Fasting and postprandial blood glucose levels were significantly reduced by ipragliflozin. In week 24, there were significant decreases from baseline in BW (-2.6 kg), waist circumference (-2.9 cm), and body fat mass (-1.9 kg) (P < 0.001). The body water mass and mineral mass were decreased significantly by 0.5 and by 0.1 kg, respectively (P < 0.001), whereas the protein mass did not change significantly. Intracellular water mass did not change significantly, whereas extracellular water mass showed a significant decrease of 0.5 kg (P < 0.001). Muscle mass did not change in the upper and lower limbs, but that of the trunk decreased significantly (P < 0.001). There was a significant decrease in the fasting triglyceride level and a significant increase in fasting high-density lipoprotein cholesterol level, while low-density lipoprotein cholesterol was unchanged. Adverse events occurred in 23.5% of the patients, with a high frequency of genital infections, such as vulvovaginal candidiasis (3.1%) and genital pruritus (1.8%). Adverse drug reactions were noted in 13.7% of the patients. CONCLUSIONS: Administration of ipragliflozin for 24 weeks improved glycemic control and decreased BW. Reduction of body fat accounted for more than 70% of the total weight loss and reduction of extracellular water accounted for about 20%.

Correction: Efficacy and Safety of Ipragliflozin in Japanese Patients With Type 2 Diabetes: Interim Outcome of the ASSIGN-K Study.

[This corrects the article DOI: 10.14740/jocmr2417w.].

Efficacy and Safety of Ipragliflozin in Japanese Patients With Type 2 Diabetes: Interim Outcome of the ASSIGN-K Study.

BACKGROUND: Ipragliflozin is a sodium-glucose co-transporter 2 inhibitor that can improve glycemic control and reduce body weight and blood pressure in patients with type 2 diabetes mellitus (T2DM). We evaluated the efficacy and safety of ipragliflozin in the real-world clinical setting, with a focus on the changes of body composition up to 3 months of treatment. METHODS: This was a prospective multicenter interventional trial. We investigated changes of the blood pressure, body composition, blood glucose, hemoglobin A1c (HbA1c), ketone bodies, lipids, and insulin after treatment with ipragliflozin (50 - 100 mg/day) for 12 weeks in Japanese patients with T2DM who showed poor glycemic control despite receiving diet and exercise therapy with or without oral antidiabetic drugs for more than 12 weeks. RESULTS: Two hundred and fifty-seven subjects were included in the efficacy analysis up to 12 weeks of treatment and 301 subjects were included in the safety analysis. From baseline to 12 weeks, HbA1c showed a change of -0.68% (95% confidence interval (CI): -0.83, -0.53) and fasting blood glucose showed a change of -23.9 mg/dL (95% CI: -30.5, -17.2), with both parameters displaying a significant reduction (P < 0.001). The difference of body weight from baseline was -1.82 kg (95% CI: -2.14, -1.50), and it also showed significant reduction (P < 0.001). Analysis of body composition revealed that body fat changed by -1.46 kg (95% CI: -1.79, -1.14, P < 0.001) and body water changed by -0.37 kg (95% CI: -0.60, -0.14, P < 0.01). Laboratory tests demonstrated improvement of liver function and the lipid profile. Adverse events (AEs) occurred in 22.6% of the subjects, with frequent events being vulvovaginal candidiasis in 2.7% and cystitis in 2.0%. Serious AEs occurred in three subjects. CONCLUSIONS: In patients with T2DM, ipragliflozin improved glycemic control after 1 month of treatment and caused weight loss by reducing body fat more than body water.

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.

Comparison of the administration of teneligliptin every day versus every other day in Japanese patients with type 2 diabetes: a randomized non-inferior test.

The half life (t1/2 ) of teneligliptin is 24.2 hours. Accordingly, we hypothesized that the administration of teneligliptin every other day might improve glycemic control. In this study, we evaluated the effectiveness of the administration of teneligliptin every other day in Japanese patients with type 2 diabetes. Fifty-one patients were randomly assigned to receive treatment with 20 mg of teneligliptin every day (Group A) or 20 mg of teneligliptin every other day (Group B) for 12 weeks. HbA1c, glycoalbumin (GA), 1,5-anhydroglucitol (1,5-AG), lipid, blood pressure, body weight, urine albumin-to-creatinine ratio, overall treatment satisfaction level, adverse events and drug adherence were all measured. Forty-seven patients completed this study, and the HbA1c, GA, and 1,5-AG levels in group B were found to be decreased to the same extent as those in group A. No distinct differences in the overall treatment satisfaction level, adverse events, or drug adherence were seen between the two groups at 12 weeks. The administration of teneligliptin every other day had a similar efficacy, patient satisfaction level, and safety compared with its administration every day. This information will be useful for reducing the economic load without changing the patients' satisfaction and glycemic control.

Is a switch from insulin therapy to liraglutide possible in Japanese type 2 diabetes mellitus patients?

BACKGROUND: To evaluate the efficacy of switching from insulin to the GLP-1 receptor agonist liraglutide in type 2 diabetes mellitus patients. METHODS: The subjects were 231 outpatients with type 2 diabetes mellitus being treated with liraglutide for the first time. For 161 patients, liraglutide was continued for 24 weeks (continuation group), and for 70 patients, liraglutide was discontinued before 24 weeks (discontinuation group). Fasting and postprandial blood glucose levels, HbA1c, body weight, and insulin dose were evaluated before the switch to liraglutide (baseline) and at 12 and 24 weeks of administration. Trends in HbA1c and weight were compared at 12 and 24 weeks of administration. Multiple regression analyses were conducted to identify clinical factors predicting a successful switch to liraglutide. RESULTS: Multiple regression analysis with ΔHbA1c as the dependent variable in the continuation group indicated that HbA1c at 12 weeks of administration decreased with higher baseline HbA1c and increased with higher baseline daily insulin doses. Multiple regression analysis with Δweight as the dependent variable indicated that Δweight at 24 weeks of liraglutide administration was higher with higher baseline daily insulin doses and longer duration of diabetes. Based on the area under the receiver operating characteristic curve, cut-off values of 19 units for daily insulin dose and nine years for duration of diabetes were identified. CONCLUSIONS: Switching from insulin to liraglutide therapy is possible for carefully selected patients. Daily insulin dosage and duration of insulin therapy appear to be clinically useful indicators for the efficacy of liraglutide therapy.

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.

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.