Association between sarcopenia and the severity of diabetic polyneuropathy assessed by nerve conduction studies in Japanese patients with type 2 diabetes mellitus

Aims/IntroductionThis study examined the association between the severity of diabetic polyneuropathy (DPN) based on the Baba classification, and sarcopenia and its related factors.Materials and MethodsThe participants were 261 patients with type 2 diabetes mellitus. DPN was classified as stages 0–4 according to the Baba classification. Sarcopenia was diagnosed based on measurements of the skeletal mass index, grip strength and walking speed, using the Asia Working Group for Sarcopenia 2019 diagnostic criteria.ResultsThe median age of the participants was 67 years, the proportion of men was 58.6%, the median estimated duration of diabetes was 10 years and the median values for glycated hemoglobin were 10.3%. With regard to DPN, the prevalence of Baba classification stages 0–2 was 90.8% (n = 237), and that of stage 3 or 4 was 9.2% (n = 24). The prevalence of sarcopenia was 19.9%. A trend toward an increase in the frequency of slow walking speed was seen as the stage of DPN progressed. The frequencies of sarcopenia and slow walking speed were higher in the group with the Baba classification stages 3 and 4 than in the group with stages 0–2. On multiple logistic regression analyses, however, DPN was not significantly related to sarcopenia and walking speed.ConclusionsAlthough severe DPN might be related to sarcopenia, the frequency of severe DPN is low in the clinical setting, indicating that its contribution to sarcopenia is modest.     

Insulin resistance limits corneal nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control

Aims/IntroductionThis study aimed to investigate whether insulin resistance (IR) in individuals with type 2 diabetes undergoing intensive glycemic control determines the extent of improvement in neuropathy.Materials and MethodsThis was an exploratory substudy of an open‐label, randomized controlled trial of individuals with poorly controlled type 2 diabetes treated with exenatide and pioglitazone or insulin to achieve a glycated hemoglobin <7.0% (<53 mmol/mol). Baseline IR was defined using homeostasis model assessment of IR, and change in neuropathy was assessed using corneal confocal microscopy.ResultsA total of 38 individuals with type 2 diabetes aged 50.2 ± 8.5 years with (n = 25, 66%) and without (n = 13, 34%) IR were studied. There was a significant decrease in glycated hemoglobin (P < 0.0001), diastolic blood pressure (P < 0.0001), total cholesterol (P < 0.01) and low‐density lipoprotein (P = 0.05), and an increase in bodyweight (P < 0.0001) with treatment. Individuals with homeostasis model assessment of IR <1.9 showed a significant increase in corneal nerve fiber density (P ≤ 0.01), length (P ≤ 0.01) and branch density (P ≤ 0.01), whereas individuals with homeostasis model assessment of IR ≥1.9 showed no change. IR was negatively associated with change in corneal nerve fiber density after adjusting for change in bodyweight (P < 0.05).ConclusionsNerve regeneration might be limited in individuals with type 2 diabetes and IR undergoing treatment with pioglitazone plus exenatide or insulin to improve glycemic control.     

Factors associated with good glycemic control among patients with type 2 diabetes mellitus

Aims/Introduction

The aim of the present study was to determine the status of glycemic control and identify factors associated with good glycemic control among diabetic patients treated at primary health clinics.

Materials and Methods

A systematic random sample of 557 patients was selected from seven clinics in the Hulu Langat District. Data were collected from patients'' medication records, glycemic control tests and structured questionnaires. Logistic regression analysis was carried out to predict factors associated with good glycemic control.

Results

Variables associated with good glycemic control included age (odds ratio 1.033; 95% confidence interval 1.008–1.059) and duration of diabetes mellitus (odds ratio 0.948; 95% confidence interval 0.909–0.989). Compared with the patients who were receiving a combination of insulin and oral antidiabetics, those receiving monotherapy (odds ratio 4.797; 95% confidence interval 1.992–11.552) and a combination of oral antidiabetics (odds ratio 2.334; 95% confidence interval 1.018–5.353) were more likely to have good glycemic control. In the present study, the proportion of patients with good glycemic control was lower than that in other published studies. Older patients with a shorter duration of diabetes who were receiving monotherapy showed better glycemic control.

Conclusions

Although self‐management behavior did not appear to influence glycemic control, diabetic patients should be consistently advised to restrict sugar intake, exercise, stop smoking and adhere to medication instructions. Greater effort by healthcare providers in the primary health clinics is warranted to help a greater number of patients achieve good glycemic control.     

吸烟对男性2型糖尿病患者血糖控制的影响

对757例男性2型糖尿病患者进行糖尿病病史、吸烟状况、体力活动、饮食控制和与糖代谢有关的实验室检查，发现每日吸烟数量与空腹血糖(FBG)、餐后2h血糖(2hPBG)、HbAic正相关。     

Factors associated with hypoglycemia unawareness and severe hypoglycemia in type 1 diabetes mellitus patients

Aims/IntroductionSeveral factors are associated with hypoglycemia unawareness and severe hypoglycemia, but few large studies have analyzed Japanese patients with type 1 diabetes. The aim of this study was to analyze the risk factors for hypoglycemia unawareness and severe hypoglycemia in Japanese type 1 diabetes patients.Materials and MethodsA self‐administered questionnaire investigated events, complications and treatments associated with hypoglycemia in patients with type 1 diabetes. Multiple logistic regression analysis of factors associated with hypoglycemia unawareness and severe hypoglycemia requiring medical treatment was carried out. The coefficient of variation (CV) of blood glucose levels was determined using blood samples collected at six outpatient visits.ResultsOf the 1,619 participants, 44.2% and 10.4% experienced hypoglycemia unawareness and severe hypoglycemia, respectively. Mean HbA1c levels in patients with hypoglycemia unawareness were lower than those in patients without hypoglycemia unawareness. The type 1 diabetes subtype, glycated hemoglobin (HbA1c) level, CV of blood glucose levels and history of severe hypoglycemia requiring medical treatment were significant independent variables predicting the presence of hypoglycemia unawareness. The glucose CV and a history of hypoglycemia unawareness were significant independent variables predicting severe hypoglycemia requiring medical treatment. In stratified analyses of patients divided into four groups according to glucose CV and HbA1c levels, the high‐glucose‐CV/low‐HbA1c group had the highest odds ratios for hypoglycemia unawareness (2.60) and severe hypoglycemia requiring medical treatment (2.55).ConclusionsThe ambulant glucose CV correlated with both hypoglycemia unawareness and severe hypoglycemia. Patients with high glucose CV and low HbA1c are at high risk of such adverse events, and their treatment strategies should be reviewed.     

Utility of indices using C‐peptide levels for indication of insulin therapy to achieve good glycemic control in Japanese patients with type 2 diabetes

Aims/Introduction: Type 2 diabetes is progressive in that therapy must be altered over time, which is partly as a result of the progressive loss of pancreatic β‐cell function. To elucidate the relationship between residual endogenous insulin secretion and the necessity of insulin therapy to achieve good glycemic control, indices using serum C‐peptide immunoreactivity (CPR) were analyzed in patients with type 2 diabetes. Materials and Methods: The data of 201 Japanese patients with type 2 diabetes who achieved the target of glycemic control during admission were analyzed retrospectively. Indices using CPR including fasting CPR (FCPR), CPR 6 min after intravenous injection of glucagon (CPR‐6 min), increment of CPR (ΔCPR), secretory unit of islet in transplantation index (SUIT) and C‐peptide index (CPI) were compared between the group requiring insulin (insulin group) and the group not requiring insulin (non‐insulin group). A receiver–operator characteristic (ROC) curve was made, and optimal cut‐off point and likelihood ratio were determined for each index. Results: All indices of CPR were lower in the insulin group compared with those in the non‐insulin group. Likelihood ratios at the optimal point of FCPR, CPR‐6 min, ΔCPR, SUIT, and CPI were 2.0, 2.1, 1.6, 2.3 and 2.8, respectively. Optimal cut‐off point of CPI was 1.1 ng/mg. Sensitivity and specificity at optimal point of CPI were 61 and 78%, respectively. Conclusions: The advantage of CPI of the indices of CPR to select insulin therapy to achieve good glycemic control was shown, but limitations of the predictive abilities of the indices using CPR should be taken into account. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00096.x, 2011)     

Prevalence and predictors of clinical inertia in patients with type 2 diabetes who were treated with a single oral antidiabetic drug

Aims/IntroductionClinical inertia, defined as a failure of healthcare providers to initiate or intensify treatment when indicated, is one of the challenges in achieving glycemic targets in type 2 diabetes patients.Materials and MethodsUsing a Japanese medical database compiled from Diagnostic Procedure Combination hospitals, this retrospective study investigated clinical inertia in type 2 diabetes patients treated with a single oral antidiabetic drug. We analyzed predictors of clinical inertia, measured the time to treatment intensification, and monitored patients'' glycemic control and renal function for 2 years. The index date was defined as the first date of hemoglobin A1c ≥7.0% during the 180 (±60) days after the first oral antidiabetic drug was prescribed.ResultsClinical inertia was identified in 35.3% of patients. The median time to treatment intensification from the index date was 75.5 days. The proportion of patients achieving hemoglobin A1c <7.0% within 2 years was 33.8% with clinical inertia, and 47.9% without clinical inertia. Multivariate logistic regression analysis showed that Charlson Comorbidity Index score and an interval between visits of ≥6 weeks significantly increased the risk of developing clinical inertia, and hyperlipidemia and higher hemoglobin A1c at baseline significantly decreased the risk.ConclusionsThis study showed that clinical inertia in type 2 diabetes patients treated with a single oral antidiabetic drug might have a lasting effect on long‐term glycemic control. Our findings will inform clinicians of the characteristics of patients associated with clinical inertia and the importance of providing appropriate treatment under clinical practice guidelines.     

Visit‐to‐visit variability in albuminuria predicts renal function deterioration in patients with type 2 diabetes

Aims/IntroductionWe aimed to study the predictive ability of visit‐to‐visit variability in albuminuria for changes in renal function in patients with type 2 diabetes mellitus.Materials and MethodsThe cohort study was carried out in a single medical center. In the model development cohort of 1008 subjects, we developed the albuminuria variability score (AVS) to evaluate the visit‐to‐visit variability in albuminuria, which was the percentage of the number of changes in the urine albumin : creatinine ratio ≥3.39 mg/mmol among all visit‐to‐visit urine albumin : creatinine ratio differences within an individual. Multivariate logistic regression was applied to predict the influence of AVS levels on the occurrence of study end‐points. In another independent validation cohort of 310 participants, survival analysis was carried out to evaluate the ability of AVS in predicting the study end‐point.ResultsIn the model development cohort, a higher AVS was associated with higher adjusted odds of having a declined or rapidly declined estimated glomerular filtration rate (eGFR) trajectory (1.84, 95% confidence interval 1.23–2.76 and 5.70, 95% confidence interval 2.28–14.25, respectively), a resultant eGFR <60 mL/min/1.73 m² (2.61, 95% confidence interval 1.63–4.16) and a >40% decline in eGFR from baseline (6.44, 95% confidence interval 2.15–19.26). In the validation cohort, a higher AVS independently predicted a 5‐year decrease of >40% in eGFR to <60 mL/min/1.73 m² (adjusted hazard ratio 3.33, 95% confidence interval 1.10–10.05). Integrated discrimination index and concordance statistics showed that AVS significantly improved the predictive ability of the models.ConclusionsVisit‐to‐visit variability in albuminuria can independently predict long‐term renal function deterioration in patients with type 2 diabetes mellitus. Further investigations are warranted to elucidate the potential clinical applications.     

Poor quality of sleep in Mexican patients with type 2 diabetes and its association with lack of glycemic control

AimsTo determine the association between sleep quality and lack of glycemic control in a Mexican population of type 2 diabetes patients.MethodsCross-sectional study. Two hundred two patients between 20 and 60 years old with a previous diagnosis of diabetes were included. Sleep quality was assessed with the Pittsburgh Sleep Quality Index and lack of glycemic control as a glycated hemoglobin A1c level ≥ 7 %. Univariate and multivariate analyses using logistic regression were performed.ResultsThe study population showed poor sleep quality and a lack of glycemic control of 70.3 % and 69.8 %, respectively. The prevalence of patients with both conditions was 52.5 %. In multivariate analysis, poor sleep quality was significantly associated with a lack of glycemic control (OR = 2.3, p = 0.030). Other associated variables were napping (p = 0.015), diabetes duration (p = 0.011), insulin use (p = 0.024), and diastolic blood pressure ≥ 85 mmHg (p = 0.029).ConclusionsThe prevalence of lack of glycemic control in the study population is high. Poor sleep quality significantly doubles the risk of lack of glycemic control, even in the presence of other risk factors.     

Effects of intermittent very‐low calorie diet on glycemic control and cardiovascular risk factors in obese patients with type 2 diabetes mellitus: A randomized controlled trial

Aims/IntroductionVery few studies assess the effectiveness of different protocols of intermittent very‐low calorie diet (VLCD) in patients with diabetes. This study was designed to compare the effects of 2 days/week and 4 days/week of intermittent VLCD on glycemic control, diabetes remission, metabolic parameters and quality of life in patients with type 2 diabetes and obesity.Materials and MethodsParticipants with obesity and type 2 diabetes were recruited and randomly assigned to three groups, consisting of control, 2 days/week and 4 days/week of intermittent VLCD. In the intermittent VLCD groups, participants received a 600‐kcal diet per day on restricted days and ad libitum food consumption on non‐restricted days. Glycemic control, rate of diabetes remission, metabolic parameters and quality of life were evaluated at baseline, weeks 2, 10 and 20.ResultsA total of 40 participants were enrolled. The mean body mass index was 30.1 ± 5.9 kg/m², and the mean glycated hemoglobin was 7.4 ± 1.2%. At week 20, there was an improvement in glycemic control in both intermittent VLCD groups with significant decreases in glycated hemoglobin levels and insulin resistance index throughout the study periods. Diabetes remission without the need for medications was equally found in 29% of participants in both intermittent VLCD groups. Serum triglyceride, bodyweight, body mass index and fat mass were also significantly decreased in both VLCD groups. No serious adverse events were encountered.ConclusionIntermittent VLCD was highly effective in achieving optimal glycemic control. The effects of 2 days/week and 4 days/week of intermittent VLCD on diabetes remission were relatively similar.     

High engagement in mobile peer support is associated with better glycemic control in type 1 diabetes: A real‐world study

Aims/IntroductionPeer support for diabetes has become convenient and interactive after the emergence of mobile health (mHealth). We aimed to evaluate the association between engagement in peer support through the mHealth app and glycemic control in type 1 diabetes patients.Materials and MethodsThis retrospective study included adults with type 1 diabetes who had joined the mobile community “TangTangQuan” since May 2018 for at least 1 year. “Like”, “comment” and “share” were the major interaction indicators of the mobile community and were used to assess engagement in peer support. The patients were divided into four engagement groups by quartile. The primary outcome was the change in glycosylated hemoglobin (HbA_1c), mean fasting blood glucose (FBG) and postprandial blood glucose (PBG) from baseline to the 12th month. Other outcomes included the change of self‐monitoring of blood glucose frequency, hypoglycemia frequency and the proportion of reaching optimal glycemic control.ResultsAmong the 693 individuals, the HbA_1c, mean FBG and PBG improved in the 12th month. Multiple regression analysis showed that higher engagement in peer support was associated with a greater reduction of HbA_1c (β = −0.45, P < 0.001) and mean FBG (β = −0.82, P < 0.001). In the subgroup of poor glycemic control, the association between engagement in peer support and glycemic improvement still remained (HbA_1c: β = −0.86, P = 0.002; FBG: β = −1.36, P = 0.001). The engagement in mobile peer support was positively correlated with educational level (odds ratio 1.42, P = 0.042), household income (odds ratio 1.43, P = 0.013) and the use of continuous subcutaneous insulin infusion (odds ratio 1.73, P = 0.009).ConclusionHigh engagement in mobile peer support was associated with better glycemic control in adults with type 1 diabetes.     

Impact of flash glucose monitoring on glycemic control varies with the age and residual β‐cell function of patients with type 1 diabetes mellitus

Aims/IntroductionWe aimed to explore the clinical factors associated with glycemic variability (GV) assessed with flash glucose monitoring (FGM), and investigate the impact of FGM on glycemic control among Chinese type 1 diabetes mellitus patients in a real‐life clinical setting.Materials and MethodsA total of 171 patients were included. GV was assessed from FGM data. A total of 110 patients wore FGM continuously for 6 months (longitudinal cohort). Hemoglobin A1c (HbA1c), fasting and 2‐h postprandial C‐peptide, and glucose profiles were collected. Changes in HbA1c and glycemic parameters were assessed during a 6‐month FGM period.ResultsIndividuals with high residual C‐peptide (HRCP; 2‐h postprandial C‐peptide >200 pmol/L) had less GV than patients with low residual C‐peptide ( 2‐h postprandial C‐peptide ≤200 pmol/L; P < 0.001). In the longitudinal cohort (n = 110), HbA1c and mean glucose decreased, time in range (TIR) increased during the follow‐up period (P < 0.05). The 110 patients were further divided into age and residual C‐peptide subgroups: (i) HbA1c and mean glucose were reduced significantly only in the subgroup aged ≤14 years during the follow‐up period, whereas time below range also increased in this subgroup at 3 months (P = 0.047); and (ii) HbA1c improved in the HRCP subgroup at 3 and 6 months (P < 0.05). The mean glucose decreased and TIR improved significantly in the low residual C‐peptide subgroup; however, TIR was still lower and time below range was higher than those of the HRCP subgroup at all time points (P < 0.05).ConclusionsHRCP was associated with less GV. FGM wearing significantly reduced HbA1c, especially in pediatric patients and those with HRCP. Additionally, the mean glucose and TIR were also found to improve.     

Comparative clinical outcomes of insulin degludec and insulin glargine 300 U/mL after switching from other basal insulins in real‐world patients with type 1 and type 2 diabetes

Aims/IntroductionTo evaluate and compare the efficacy of insulin degludec (IDeg) and insulin glargine 300 U/mL (Gla300) 6 months after switching from other basal insulins by assessing the changes in glycated hemoglobin (HbA1c), body mass index (BMI), and insulin doses in patients with type 1 and type 2 diabetes in a real‐world clinical setting.Materials and MethodsA total of 307 patients with type 1 diabetes and 294 patients with type 2 diabetes with HbA1c >7.0% were studied. Adjusted mean changes in HbA1c, BMI, and insulin doses were compared between IDeg (IDeg group) and Gla300 (Gla300 group) switchers. Multivariable logistic regression analyses were carried out to examine whether the IDeg or Gla300 group was associated with HbA1c or insulin dose reduction and BMI gain.ResultsHbA1c was significantly decreased in both the IDeg and Gla300 groups. Adjusted mean changes in HbA1c (approximately −0.3% and −0.5% in type 1 diabetes and type 2 diabetes patients, respectively) and BMI were similar between both groups. The mean change in insulin dose was slightly larger for dose reduction in the IDeg group than in the Gla300 group. Multivariable logistic regression models showed that the IDeg group was significantly associated with insulin dose reduction after adjusting for basal insulin type, insulin dose, and number of basal insulin injections at baseline and other confounding factors.ConclusionsThe current study suggested that IDeg and Gla300 have similar effects in reducing HbA1c and gaining BMI after switching from other basal insulins in Japanese patients with type 1 diabetes and type 2 diabetes. IDeg selection was associated with insulin dose reduction.     

Improved glycemic control and reduced bodyweight with exenatide: A double‐blind,randomized, phase 3 study in Japanese patients with suboptimally controlled type 2 diabetes over 24 weeks

Aims/Introduction:  To evaluate the efficacy and safety of the glucagon‐like peptide‐1 receptor agonist, exenatide, in Japanese patients with type 2 diabetes mellitus suboptimally controlled despite therapeutic doses of a sulfonylurea alone or combined with a biguanide or thiazolidinedione.Materials and Methods:  Patients were randomized to a placebo or exenatide, either 5 or 10 μg, given subcutaneously b.i.d. in addition to oral therapy. Patients randomized to 10 μg exenatide received 5 μg b.i.d. for the first 4 weeks, followed by 10 μg b.i.d. for the last 20 weeks.Results:  A total of 179 patients received the study drug and composed the full analysis set (n = 35, placebo; n = 72, exenatide 5 μg; n = 72, exenatide 10 μg; 68% male; 58 ± 10 years; body mass index 25.5 ± 4.1 kg/m²; HbA_1c 8.2 ± 0.9%; means ± standard deviations). Baseline to end‐point (least‐squares means ± standard errors) HbA_1c changes (%) were −0.28 ± 0.15 (placebo), −1.34 ± 0.11 (exenatide 5 μg) and −1.62 ± 0.11 (exenatide 10 μg) (both P < 0.001, exenatide vs placebo). Baseline to end‐point bodyweight changes (kg) were −0.47 ± 0.39 (placebo), −0.39 ± 0.28 (exenatide 5 μg) and −1.54 ± 0.27 (exenatide 10 μg; P = 0.026, exenatide 10 μg vs placebo). Nausea, generally mild to moderate, was reported in 8.6% (placebo), 25.0% (exenatide 5 μg) and 36.1% (exenatide 10 μg) of patients. Mild to moderate hypoglycemia was reported in 22.9% (placebo), 51.4% (exenatide 5 μg) and 58.3% (exenatide 10 μg) of patients.Conclusions:  Over 24 weeks, exenatide vs the placebo improved glycemic control, reduced bodyweight (10 μg) and was well tolerated in Japanese patients with type 2 diabetes mellitus suboptimally controlled, despite oral therapy including a sulfonylurea. This trial was registered with ClinicalTrials.gov (no. {"type":"clinical-trial","attrs":{"text":"NCT00577824","term_id":"NCT00577824"}}NCT00577824). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00084.x, 2011)     

Effects of concomitant drugs on sitagliptin-mediated improvement in glycemic control in Japanese patients with type 2 diabetes

AimsWe investigated to clarify factors associated with the efficacy of sitagliptin, a dipeptidyl peptidase (DPP)-IV inhibitor, for glycemic control including the confounding effect of concomitant drugs in patients with type 2 diabetes.MethodsWe included type 2 diabetes patients with HbA1c levels of ≥7% who were not under insulin treatment and were administered sitagliptin (50 mg/day for 6 months). Reduction or discontinuation of insulin sensitizers was not permitted during the study period. Outcomes included HbA1c level variations and attaining a target HbA1c level of <7%. Associated factors with each outcome were examined using multivariate analysis.ResultsOf the 313 patients enrolled in this study, 147 (47.0%) attained HbA1c levels of <7%. High baseline HbA1c levels were associated with HbA1c level variations but inversely associated with attaining the target HbA1c level of <7%. Concomitant use of an insulin sensitizer and a α-glucosidase inhibitor and maintenance of the baseline dose of concomitant drugs were significantly associated with each outcome.ConclusionsOur results suggest that concomitant sitagliptin administration (50 mg/day) will improve glycemic control if treatment is initiated before HbA1c levels deteriorate. Other medication should be continued at initiation of sitagliptin administration.     

Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A subgroup analysis by baseline variables in the PIONEER 9 and PIONEER 10 trials

Aims/IntroductionTo assess the impact of baseline characteristics on the efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes.Materials and MethodsIn the Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) 9 and 10 trials, Japanese patients were randomized to once‐daily oral semaglutide (3, 7, or 14 mg) or a comparator (placebo or once‐daily subcutaneous liraglutide 0.9 mg in PIONEER 9; once‐weekly subcutaneous dulaglutide 0.75 mg in PIONEER 10) for 52 weeks, with 5 weeks of follow up. An exploratory analysis grouped patients in each trial according to baseline glycated hemoglobin (HbA_1c; ≤8.0, >8.0–≤9.0, or >9.0%), body mass index (<25, ≥25–<30, or ≥30 kg/m²) and, for PIONEER 10 only, by background medication (sulfonylurea, glinide, thiazolidinedione, α‐glucosidase inhibitor, sodium‐glucose cotransporter 2 inhibitor). Efficacy (changes from baseline to week 26 in HbA_1c and bodyweight) and safety were assessed.ResultsSeven hundred and one patients were included (PIONEER 9: N = 243; PIONEER 10: N = 458). In both trials, HbA_1c reductions increased as baseline HbA_1c increased; there were no other apparent patterns between the variables investigated and HbA_1c or bodyweight changes. There was one statistically significant subgroup interaction between baseline HbA_1c and estimated treatment differences in bodyweight change for oral semaglutide 14 mg versus placebo in PIONEER 9 (P = 0.0286). Baseline HbA_1c, baseline body mass index and background medication did not appear to affect the proportions of patients reporting adverse events.ConclusionsOral semaglutide is effective across a range of baseline subgroups of Japanese patients with type 2 diabetes, with no unexpected safety findings.