Indirect comparison of efficacy and safety of chiglitazar and thiazolidinedione in patients with type 2 diabetes: A meta-analysis.

BACKGROUND: Chiglitazar is an emerging pan-agonist of all peroxisome proliferator activated receptors (PPAR)-α, δ and γ, and has therapeutic potential for type 2 diabetes (T2D). However, to date, no clinical studies or meta-analyses have compared the efficacy and safety of chiglitazar and traditional PPAR-γ agonist thiazolidinediones (TZDs). A meta-analysis concerning this topic is therefore required. AIM: To compare the efficacy and safety of chiglitazar and TZD in patients with T2D. METHODS: PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials, Reference Citation Analysis and Clinicaltrial.gov websites were searched from August 1994 to March 2022. Randomized controlled trials (RCTs) of chiglitazar or TZD vs placebo in patients with T2D were included. Indirect comparisons and sensitivity analyses were implemented to evaluate multiple efficacy and safety endpoints of interest. RESULTS: We included 93 RCTs that compared TZD with placebo and one that compared chiglitazar with placebo. For efficacy endpoints, the augmented dose of chig-litazar resulted in greater reductions in hemoglobin (Hb)A1c [weighted mean difference (WMD) = -0.15%, 95% confidence interval (CI): -0.27 to -0.04%], triglycerides (WMD = -0.17 mmol/L, 95%CI: -0.24 to -0.11 mmol/L) and alanine aminotransferase (WMD = -5.25 U/L, 95%CI: -8.50 to -1.99 U/L), and a greater increase in homeostasis model assessment-ß (HOMA-ß) (WMD = 17.75, 95%CI: 10.73-24.77) when compared with TZD treatment. For safety endpoints, the risks of hypoglycemia, edema, bone fractures, upper respiratory tract infection, urinary tract infection, and weight gain were all comparable between the augmented dose of chiglitazar and TZD. In patients with baseline HbA1c ≥ 8.5%, body mass index ≥ 30 kg/m2 or diabetes duration < 10 years, the HbA1c reduction and HOMA-ß increase were more conspicuous for the augmented dose of chiglitazar compared with TZD. CONCLUSION: Augmented dose of chiglitazar, a pan-activator of PPARs, may serve as an antidiabetic agent with preferable glycemic and lipid control, better ß-cell function preserving capacity, and does not increase the risk of safety concerns when compared with TZD.

Alcohol intake and dyslipidemia in male patients with hypertension and diabetes enrolled in a China multicenter registry.

Alcohol consumption is a proven risk factor of dyslipidemia. In the present analysis, we investigated the association of alcohol intake with dyslipidemia, an emerging epidemic in China, in male patients with hypertension and diabetes mellitus. Our study participants were from a nationwide registry (n = 1181). A questionnaire was administered to collect information on alcohol intake. Dyslipidemia was defined as an elevated concentration of serum triglycerides (≥2.3 mmol/L), total (≥6.2 mmol/L) or low-density lipoprotein (LDL) cholesterol (≥4.1 mmol/L), or a reduced high-density lipoprotein (HDL) cholesterol (< 1.0 mmol/L). Serum concentrations of triglycerides (1.60 mmol/L) and total (4.93 mmol/L) and LDL cholesterol (2.95 mmol/L) were highest with current usual drinking, with a significant P value for trend from never (n = 679) to ever (n = 107) and to rare (n = 187) and usual drinkers (n = 208, P ≤ .002). Serum HDL cholesterol (1.13 mmol/L) was lowest in ever drinkers, with a nonsignificant P value for trend (P = .22). The prevalence was highest in usual drinkers for hypertriglyceridemia (27.4%) and total (12.5%) and LDL hypercholesterolemia (8.7%), and in ever drinkers for low HDL cholesterol (34.6%). The P value for trend was significant for hypertriglyceridemia and total hypercholesterolemia (P ≤ .01), but not for LDL hypercholesterolemia or low HDL cholesterol (P ≥ .26). The between-province ecological analysis showed that the proportion of usual drinking was significantly associated with the prevalence of any dyslipidemia across 10 China provinces (r = .42, P < .0001). In conclusion, alcohol drinkers showed a worse lipid profile in patients with hypertension and diabetes mellitus. Usual drinking ecologically explained the between-province variation in the prevalence of dyslipidemia.

Association between dyslipidemia and antihypertensive and antidiabetic treatments in a China multicenter study.

Dyslipidemia is an emerging disease in China, especially in the presence of hypertension and diabetes mellitus. We investigated the association of dyslipidemia with the use of antihypertensive and antidiabetic agents. The study participants (n = 2423) were hypertensive and diabetic patients enrolled in a China nationwide registry. Serum mean ± (SD, except for serum triglycerides, median [interquatile range]) concentrations were 1.38 (0.97-2.02) mmol/L, 4.85 ± 1.12 mmol/L, 1.30 ± 0.36 mmol/L, and 2.89 ± 0.92 mmol/L for triglycerides and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, respectively. The prevalence of dyslipidemia was 18.9%, 13.5%, 16.6%, and 37.7% for hypertriglyceridemia (serum triglycerides ≥2.3 mmol/L), hypercholesterolemia (total cholesterol ≥6.2 mmol/L or LDL cholesterol ≥4.1 mmol/L), low HDL cholesterol (HDL cholesterol <1.0 mmol/L), and any of the three lipid disorders, respectively. Treated (n = 1647), compared with untreated hypertensive patients (n = 303), had a significantly (P ≤ .0006) lower serum total, LDL, and HDL cholesterol, but similar serum triglycerides (P = .20). Treated (n = 1325), compared with untreated diabetic patients (n = 238), had a significantly (P ≤ .004) lower serum triglycerides, and total and LDL cholesterol, but similar serum HDL cholesterol (P = .81). After adjustment, the odds ratios (OR) were significant for hypercholesterolemia (OR 0.76, 95% confidence interval [CI] 0.58-0.997, P = .048) and low HDL cholesterol (OR 1.56, CI 1.19-2.03, P = .001) in treated versus untreated hypertension, and for low HDL cholesterol (OR 1.50, CI 1.18-1.89, P = .0008) in treated versus untreated diabetes. In conclusion, the prevalence of dyslipidemia differed between treated and untreated hypertension and diabetes.

A Two-Stage Study Identifies Two Novel Polymorphisms in PRKAG2 Affecting Metformin Response in Chinese Type 2 Diabetes Patients.

OBJECTIVE: Individual differences in glycemic response to metformin in antidiabetic treatment exist widely. Although some associated genetic variations have been discovered, they still cannot accurately predict metformin response. In the current study, we set out to investigate novel genetic variants affecting metformin response in Chinese type 2 diabetes (T2D) patients. METHODS: A two-stage study enrolled 500 T2D patients who received metformin, glibenclamide or a combination of both were recruited from 2009 to 2012 in China. Change of HbA1c, adjusted by clinical covariates, was used to evaluate glycemic response to metformin. Selected single nucleotide polymorphisms (SNPs) were genotyped using the Infinium iSelect and/or Illumina GoldenGate genotyping platform. A linear regression model was used to evaluate the association between SNPs and response. RESULTS: A total of 3739 SNPs were screened in Stage 1, of which 50 were associated with drug response. Except for one genetic variant preferred to affect glibenclamide, the remaining SNPs were subsequently verified in Stage 2, and two SNPs were successfully validated. These were PRKAG2 rs2727528 (discovery group: ß=-0.212, P=0.046; validation group: ß=-0.269, P=0.028) and PRKAG2 rs1105842 (discovery group: ß=0.205, P=0.048; validation group: ß=0.273, P=0.025). C allele carriers of rs2727528 and C allele carriers of rs1105842 would have a larger difference of HbA1c level when using metformin. CONCLUSION: Two variants rs2727528 and rs1105842 in PRKAG2, encoding γ2 subunit of AMP-activated protein kinase (AMPK), were found to be associated with metformin response in Chinese T2D patients. These findings may provide some novel information for personalized pharmacotherapy of metformin in China.

Age-stratified association of blood pressure with albuminuria and left ventricular hypertrophy in patients with hypertension and diabetes mellitus.

PURPOSE: We investigated associations of blood pressure (BP) with albuminuria and left ventricular hypertrophy (LVH) in young, middle and older aged patients with hypertension and/or diabetes mellitus. MATERIALS & METHODS: Study participants were treated patients with hypertension or diabetes, enrolled in a China nationwide registry. The 2510 patients were classified into young (<45 years, n = 345), middle (45-64 years, n = 1383) and older (≥65 years, n = 782) age groups. Clinic BP was measured three times consecutively on each of the two clinic visits. These six readings were averaged for analyses. Albuminuria was defined as a urinary albumin-to-creatinine ratio of ≥30 mg/g. LVH was assessed by the electrocardiogram (ECG) Cornell product and voltage methods. RESULTS: The prevalence of albuminuria and ECG-LVH was 17.8 and 6.5%, respectively. Mean (±SD) systolic/diastolic BP was 132.0 ± 16.5/85.2 ± 11.9 mmHg, 136.8 ± 17.9/81.7 ± 11.2 mmHg, and 139.8 ± 16.7/75.8 ± 10.4 mmHg in the young, middle and older age groups. In the young age group, the prevalence of albuminuria increased from 8.8% in systolic/diastolic BP <120/80 mmHg to 14.6, 16.0% and 16.5% in 120-129/80-84, 130-139/85-89 and ≥140/90 mmHg, respectively. The corresponding values were 8.9, 7.0, 18.1 and 22.2%, respectively, in the middle age group, and 21.2, 15.5, 16.4 and 24.4%, respectively, in the older age group. Adjusted analyses confirmed the J-shaped relation between BP and albuminuria in the older but not young age group. The prevalence of ECG-LVH was significantly (p for trend ≤0.04) higher with increasing BP similarly in all age groups. CONCLUSIONS: The association between BP and organ damage seems to differ in young, middle and older aged patients for albuminuria but not ECG-LVH.

Treatment Effects of Short-Term Continuous Positive Airway Pressure on Blood Glucose Control in Type 2 Diabetic Patients with Obstructive Sleep Apnea Syndrome.

PURPOSE: The study aimed at assessing glucose control measured with a continuous glucose monitoring system (CGMS) before and after short-term continuous positive airway pressure (CPAP). MATERIALS AND METHODS: Twenty-four type 2 diabetic patients (T2DM) with Obstructive sleep apnea syndrome (OSAS) (mean age 55.0 ± 9.0 years; BMI 29.5 ± 5.2 kg/m2) were admitted and kept under diet control for 2 days, then underwent 2 overnight polysomnographies: a diagnostic study and one with CPAP titration. Then they were treated by CPAP during sleep for the following three nights. Participants were divided into subgroup D (only diet control) and subgroup M (with DM medication). CGMS was utilized over the last five days. Glucose control was also assessed with plasma insulin and a clinical measure of insulin resistance (HOMA-IR) index. RESULTS: The mean (±SD) apnea-hypopnea index (AHI) at diagnostic polysomnography was 51.2 ± 22.4 (range 10-88) events/h. CPAP treatment in the subjects with OSAS resulted in the index of oxygenation desaturations being reduced from 33.3 ± 20.1 to 1.1 ± 1.6 (P =0.00). CGMS showed mean 24-hours glucose values significantly lower after CPAP treatment than at baseline in both subgroups (7.97±1.31 vs 7.52±0.94, P=0.033 in subgroup D; and 7.72±1.51 vs 7.17±1.21, P=0.05 in subgroup M), as the fasting plasma insulin levels and HOMA-IR were also decreased significantly after CPAP treatment (13.0 ± 7.5µU/mL vs 10.8 ± 5.4µU/mL, P=0.044; and 4.2 ± 2.2 vs 3.1±1.7, P=0.003, respectively). Standard deviation (SD) and mean amplitude of glucose excursions (MAGE) were also decreased in the subgroup D (1.91 ± 1.10 vs 1.61 ± 1.20, P=0.014; 1.26 ± 1.13 vs 1.01 ± 0.98, P=0.008, respectively) only. CONCLUSION: Short-term CPAP treatment in OSAS with type 2 diabetic patients is accompanied by a decrease in blood glucose level and improved insulin sensitivity. Glucose variability was reduced but only in the patients with diet control.

Type 1 diabetes induced by immune checkpoint inhibitors.

With the increasing use of immune checkpoint inhibitors (ICI) including anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) in cancers, ICI-induced type 1 diabetes has been reported throughout the world. In this review, we aim to summarize the characteristics of this disease and discuss the mechanism of it. As an immune-related adverse event, type 1 diabetes developed after the administration of anti-PD-1 or anti-PD-ligand 1 (PD-L1) in the combination with or without anti-CTLA-4. It usually presented with acute onset, and 62.1% of the reported cases had diabetic ketoacidosis. Only a third of them had positive autoantibodies associated with type 1 diabetes. Susceptible HLA genotypes might be associated. T-cell-stimulation by blocking of the interaction of PD-1 and PD-L1 in pancreatic ß cells was the main mechanism involved in the pathology. Insulin was the only effective treatment of ICI-induced type 1 diabetes. In conclusions, ICI-induced type 1 diabetes is a potentially life-threating adverse event after the immunotherapy of cancers. Screening and early recognition is important. Further investigation of the mechanism may help to better understand the pathology of type 1 diabetes.

Effects of Incretin-based Therapies on Weight-related Indicators among Patients with Type 2 Diabetes: A Network Meta-analysis.

OBJECTIVE: To evaluate the effects of incretin-based therapies on body weight as the primary outcome, as well as on body mass index (BMI) and waist circumference (WC) as secondary outcomes. METHODS: Databases including Medline, Embase, the Cochrane Library, and clinicaltrials.gov (www.clinicaltrials.gov) were searched for randomized controlled trials (RCTs). Standard pairwise meta-analysis and network meta-analysis (NMA) were both carried out. The risk of bias (ROB) tool recommended by the Cochrane handbook was used to assess the quality of studies. Subgroup analysis, sensitivity analysis, meta-regression, and quality evaluation based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were also performed. RESULTS: A total of 292 trials were included in this study. Compared with placebo, dipeptidyl-peptidase IV inhibitors (DPP-4Is) increased weight slightly by 0.31 kg [95% confidence interval ( CI): 0.05, 0.58] and had negligible effects on BMI and WC. Compared with placebo, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lowered weight, BMI, and WC by -1.34 kg (95% CI: -1.60, -1.09), -1.10 kg/m 2 (95% CI: -1.42, -0.78), and -1.28 cm (95% CI: -1.69, -0.86), respectively. CONCLUSION: GLP-1 RAs were more effective than DPP-4Is in lowering the three indicators. Overall, the effects of GLP-1 RAs on weight, BMI, and WC were favorable.

Blood pressure and glucose control and the prevalence of albuminuria and left ventricular hypertrophy in patients with hypertension and diabetes.

We investigated association between blood pressure and glucose control and the prevalence of albuminuria and left ventricular hypertrophy (LVH) in patients with hypertension and diabetes. Our study participants were treated patients with both diseases, enrolled in a China nationwide registry. The 773 patients were classified into four groups according to the control status of hypertension (systolic/diastolic blood pressure [BP] ≤140/90 mm Hg) and diabetes (HbA1c <7.0%): both uncontrolled (n = 208), only diabetes (n = 175) or hypertension controlled (n = 172), and both controlled (n = 218). Albuminuria was defined as a urinary albumin-to-creatinine ratio of ≥30 mg/g. LVH was assessed by the electrocardiogram Cornell product method. Antihypertensive therapy was not different between the four groups (P ≥ .48). The use of insulin alone or insulin plus oral antidiabetic agents was significantly higher than those with both diseases controlled (P ≤ .02). Patients with controlled hypertension and diabetes had a significantly (P < .0001) lower prevalence of albuminuria (odds ratio 0.22, 95% confidence interval 0.11-0.43) than those with both diseases uncontrolled. Intensive BP control to <130/80 mm Hg was associated with lower risks of albuminuria in all patients (P = .001) and patients with HbA1c <7.0% (P = .048). Intensive glycemic control to HbA1c <6.5% was also associated with a significantly lower risk of albuminuria in all patients (P = .01), but not those with controlled BP (P = .43). Similar trends were observed for LVH, but statistical significance was not achieved on either intensive control condition (P ≥ .07). In patients with hypertension and diabetes, blood pressure and glucose control were associated with a lower prevalence of albuminuria and LVH, especially when achieving a more stringent target.

Search for clinical predictors of good glycemic control in patients starting or intensifying oral hypoglycemic pharmacological therapy: A multicenter prospective cohort study.

AIMS: Our aim was to search for clinical predictors of good glycemic control in patients starting or intensifying oral hypoglycemic pharmacological therapy. METHODS: A multicenter, prospective cohort of 499 diabetic subjects was enrolled in this study: patients with newly diagnosed diabetes (NDM group) or poor glycemic control with oral antidiabetic drugs (OADs) (PDM group). All subjects then started or intensified OADs therapy and followed up for 91 days. Glycemic control was determined according to HbA1c at day 91 with HbA1c <7% considered good. RESULTS: The proportions of patients with good glycemic control after follow up for 91 days were 66.9% and 34.8% in NDM group and PDM group respectively. Logistic regression analysis showed that the change in GA at 28 days was the only predictor of good glycemic control in NDM patients (OR = 1.630, 95% CI 1.300-2.044, P < 0.001). In PDM patients, changes in GA at 28 days, CPI, baseline HbA1c, diabetic duration, and BMI were all independent predictors of good glycemic control (All P < 0.05). CONCLUSIONS: GA decline is a good predictor of future success in newly diagnosed patients. In patients intensifying therapy, beside GA decline, other individualized clinical characteristics should also be considered.

A nationwide assessment of blood pressure control and the associated factors in Chinese type 2 diabetes mellitus patients.

A subgroup analysis of the nationwide, cross-sectional 3B STUDY was performed to understand the current blood pressure (BP) control status and treatment patterns in Chinese diabetes patients as well as to identify factors associated with BP control. The demographic data, anthropometric parameters, and laboratory results were collected from 24 512 type 2 diabetes patients. The BP goal was a systolic BP <130 mm Hg and a diastolic BP <80 mm Hg regardless of a history of hypertension or current antihypertensive treatment. The overall prevalence of hypertension was 59.9% with geographical differences. Among the diabetes patients with hypertension, 76.9% received antihypertensive medicines. Calcium channel blockers (39.3%), angiotensin II receptor antagonists (26.6%), and then ß-blockers (14.0%) or angiotensin-converting enzyme inhibitors (13.6%) were frequently used for BP control. Only 17.5% (n = 2658) of diabetes patients with hypertension reached the recommended target BP. Body mass index <24 kg/m2 , urban resident, frequent physical activity, good adherence to medication, comorbidity with cardiovascular disease, achieving glycemic goal (HbA1c <7.0%), achieving lipid goal (low-density lipoprotein cholesterol <2.59 mmol/L) were independent factors that predicted achievement of target BP goal. On the contrary, comorbidity with chronic kidney disease predicted failure to achieve target BP goal. Patients who were treated in a cardiology department or lived in the North were more likely to achieve BP goals. A considerable proportion of diabetic patients failed to achieve guideline-recommended BP targets. More aggressive efforts should be made to overcome the diverse barriers and facilitate the optimization of diabetes management.

Comparison between newly diagnosed hypertension in diabetes and newly diagnosed diabetes in hypertension.

BACKGROUND: Hypertension and diabetes mellitus are often jointly present, especially in early onset cases of either disease. We investigated clinical characteristics of hypertensive patients with newly diagnosed diabetes and diabetic patients with newly diagnosed hypertension. METHODS: Our study subjects were recruited in a China nationwide multicenter registry of hypertension and diabetes (n = 2510). We performed logistic regression to compare patients seen for hypertension in cardiology, with newly diagnosed diabetes (n = 137) and patients seen for diabetes mellitus in endocrinology, with newly diagnosed hypertension (n = 155). Albuminuria was defined as a urinary albumin-to-creatinine ratio of ≥ 30 mg/g, and left ventricular hypertrophy according to the Cornell product index. RESULTS: These two groups of patients with both hypertension and diabetes mellitus were similar in most of the characteristics (P ≥ 0.06). However, hypertensive patients with newly diagnosed diabetes, compared to diabetic patients with newly diagnosed hypertension, had a significantly greater body mass index (26.3 vs. 25.4 kg/m2, P = 0.03) and slower heart rate (73.7 vs. 78.1 beats/min, P = 0.01). In logistic regression analyses adjusted for sex (48.3% women) and age (mean 60.0 ± 11.5 years), the odds ratio for newly diagnosed diabetes mellitus versus newly diagnosed hypertension was 1.27 (95% CI 1.03-1.56) and 0.80 (95% CI 0.66-0.96) for body mass index (+ 3 kg/m2) and heart rate (+ 10 beat/min), respectively. Hypertensive patients with newly diagnosed diabetes also had a lower prevalence of albuminuria (16.0% vs. 30.1%, P = 0.02) and slightly and non-significantly higher prevalence of left ventricular hypertrophy (5.1% vs. 1.9%, P = 0.14) than diabetic patients with newly diagnosed hypertension. CONCLUSIONS: Earlier or later onset of hypertension than diabetes mellitus may have different risk factors and organ damage.

Associations of Bone Mineral Density and Bone Metabolism Indices with Urine Albumin to Creatinine Ratio in Chinese Patients with Type 2 Diabetes.

OBJECTIVE: To identify correlations of bone mineral density (BMD) and bone metabolism indices with the urine albumin to creatinine ratio (ACR) as an indicator of nephropathy in Chinese patients with type 2 diabetes (T2D). METHODS: In this retrospective analysis, 297 patients with T2D were divided into 3 groups according to the urine ACR. Patients' data were analyzed to identify associations of general conditions, blood glucose level, lipid levels, and uric acid level with BMD and bone metabolism indices. RESULTS: BMD at every location tested (femoral neck, trochanter, inside hip, Ward's triangle, total hip, and lumbar vertebrae) was negatively correlated with the urine ACR (all p<0.05). Osteocalcin, beta-C-terminal telopeptide (ß-CTX), and procollagen type 1 N- peptide (P1NP) were positively correlated with urine ACR (all p<0.05). Finally, 25-hydroxyvitamin D [25(OH)D] was negatively correlated with urine ACR (p<0.05). Multiple regression analysis with adjustment for age, body mass index, disease duration, and other clinical measurements revealed no significant correlation between urine ACR and BMD measurements or ß-CTX (p>0.05). However, significant correlations remained between urine ACR and osteocalcin, P1NP, and 25(OH)D (p<0.05). The same results were obtained for postmenopausal women specifically, with the exception of a significant correlation between the ACR and ß-CTX (p<0.05). CONCLUSION: In the early stage of diabetic nephropathy, BMD changes and bone transformation acceleration may occur, and the acceleration of bone transformation may occur before the change in BMD. Therefore, it is important to monitor bone metabolism indices in the early stage of diabetic nephropathy in T2D patients.

Blood glucose profiles in East Asian and Caucasian injection-naive patients with type 2 diabetes inadequately controlled on oral medication: a pooled analysis.

AIM: The primary objective of this study was to compare blood glucose (BG) excursions between East Asian and Caucasian patients with type 2 diabetes mellitus (T2DM) who were injection-naive, had inadequate glycemic control with oral antihyperglycemic medications, and who required initiation with injectable therapy. METHODS: This retrospective pooled analysis included individual patient data from completed clinical trials (Insulin lispro injection/dulaglutide development programs, first patient visit ≥1997). All included patients were ≥18 years, were East Asian or Caucasian, and had data for self-monitored BG at baseline. The primary outcome, BG excursion at baseline (least-squares mean, standard error), was compared between patient groups using an analysis of covariance with race as the fixed effect. Independent covariates included baseline body weight, baseline HbA1c, age, and duration of T2DM. RESULTS: Caucasian (n = 6779) and East Asian (n = 1638) patients from 21 trials were included. BG excursions were significantly higher for East Asian than Caucasian patients at breakfast (4.03 [0.075] vs 2.59 [0.045] mmol/L), lunch (3.37 [0.080] vs 1.43 [0.049] mmol/L), and dinner (3.16 [0.080] vs 1.74 [0.047] mmol/L) (P < 0.001 adjusted analyses). Similar findings were observed for the unadjusted analyses. At each time point, postprandial BG was significantly higher for East Asian than Caucasian patients (with adjusted and unadjusted analyses). CONCLUSION: These findings suggest that BG excursion and postprandial BG are higher among East Asian patients with T2DM than Caucasian patients. In addition, these findings may help clinicians select appropriate treatments for East Asian patients with T2DM who require injection therapy.

Comparison of Placebo Effect between Asian and Caucasian Type 2 Diabetic Patients: A Meta-Analysis.

BACKGROUND: Placebo was defined as any therapy that is used for its nonspecific psychological and physiologic effect but has no specific pharmacologic impact on the condition being treated. Besides medication therapies, studies have found that the optimal dietary approach as well as physical activity and education are useful to control hyperglycemia in patients with type 2 diabetes (T2DM). The aim of this study was to evaluate the placebo effects of antidiabetic therapies in Asian and Caucasian T2DM patients and make a comparison between the two ethnicities. METHODS: A search using the MEDLINE database, EMBASE, and Cochrane Database was performed, from when recording began until December 2016. The main concepts searched in English were sulfonylurea (SU); alpha glucosidase inhibitors (AGI); metformin (MET); thiazolidinediones (TZD); dipeptidyl peptidase-4 inhibitors (DPP-4i); sodium-glucose cotransporter 2 inhibitors (SGLT2i); glucagon-like peptide-1 receptor agonist (GLP-1RA); type 2 diabetes (T2DM); placebo controlled; and randomized controlled trials. Using the Cochrane instrument, we evaluated the adequacy of randomization, allocation concealment procedures, and blinding. RESULTS: This study included 63 studies with a total of 7096 Asian patients involved and 262 studies with a total of 27,477 Caucasian patients involved. In Caucasian population, the use of placebo led to significant reductions of glycosylated hemoglobin (HbA1c), -0.683% (P = 0.008) in SU monotherapy treatment, -0.193% (P = 0.001) in DPP-4i treatment, and -0.230% (P < 0.001) in SGLT2i treatment, respectively. In Asian population, the use of placebo resulted in significant decreases of HbA1c, -0.162% (P = 0.012) in DPP-4i treatment and -0.269% (P = 0.028) in GLP-1RA add-on therapy, respectively. The placebo also significantly reduced body weight. In Caucasian population, placebo use resulted in 0.833 kg (P = 0.006) weight loss by SU treatment and 0.953 kg (P = 0.006) weight loss by GLP-1RA treatment. In Asian population, the placebo led to a weight change of 0.612 kg (P < 0.001) by GLP-1RA analog treatment. The changes of HbA1c and weight due to the placebo effect in other treatments were not significant in both Asian and Caucasian population. Comparisons of the placebo effect on HbA1c change and weight change in each treatment group indicated that no significant difference was found between Asian and Caucasian population. CONCLUSIONS: The overall differences of the placebo effect on HbA1c changes as well as on body weight changes were not significant between Asian and Caucasian T2DM patients. The placebo effect on HbA1c changes and weight changes was not associated with baseline age, gender, baseline body mass index, baseline HbA1c, duration of diabetes, or study duration.

Dose titration model and correlative factors analysis in Chinese patients with type-2 diabetes on basal insulin - results from an Observational Registry of Basal Insulin Treatment study.

INTRODUCTION: This study evaluates an insulin dose titration model and factors that impact insulin dose adjustment in Chinese adults with type-2 diabetes, who receive basal insulin in real-world settings. MATERIAL AND METHODS: A total of 19,894 patients from the ORBIT study were included. These patients were divided into four groups, according to the type of insulin dose adjustment: no insulin titration (group A), self-titration (group B), physician-led insulin titration (group C), and combined physician and patient-led insulin titration (group D). Data were collected and compared at baseline and after six months of treatment. RESULTS: A total of 12,865 patients completed the visits and were included in the analysis. Among these patients, 3187 (24.8%), 1971 (15.3%), 5165 (40.1%), and 2542 (19.8%) patients were included in groups A, B, C, and D, respectively. The multivariate logistic regression analysis revealed that the duration of diabetes, body mass index, microvascular complications, inpatient days, HbA1C level, and self-monitoring of blood glucose (SMBG) were positively correlated with insulin titration in group B, C, and D, compared with group A. The number of inpatient days and outpatient visits were positively correlated with dose adjustment for physician-led titration, while this was negatively correlated for self-titration. Self-titration encouraged by physicians and home blood glucose monitoring were positively correlated with self-titration and the combined physician and patient-led titration. CONCLUSIONS: High HbA1C level, SMBG, long disease duration, microvascular complications, and the encouragement of physicians while initiating insulin use prompt patients to perform dose adjustments in real-world settings.