Efficacy and safety of ipragliflozin as an add-on therapy to sitagliptin and metformin in Korean patients with inadequately controlled type 2 diabetes mellitus: A randomized controlled trial.

AIM: To evaluate the efficacy and safety of ipragliflozin vs placebo as add-on therapy to metformin and sitagliptin in Korean patients with type 2 diabetes mellitus (T2DM). METHODS: This double-blind, placebo-controlled, multi-centre, phase III study was conducted in Korea in 2015 to 2017. Patients were randomized to receive either ipragliflozin 50 mg/day or placebo once daily for 24 weeks in addition to metformin and sitagliptin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to end of treatment (EOT). RESULTS: In total, 143 patients were randomized and 139 were included in efficacy analyses (ipragliflozin: 73, placebo: 66). Baseline mean (SD) HbA1c levels were 7.90 (0.69)% for ipragliflozin add-on and 7.92 (0.79)% for placebo. The corresponding mean (SD) changes from baseline to EOT were -0.79 (0.59)% and 0.03 (0.84)%, respectively, in favour of ipragliflozin (adjusted mean difference -0.83% [95% CI -1.07 to -0.59]; P < .0001). More ipragliflozin-treated patients than placebo-treated patients achieved HbA1c target levels of <7.0% (44.4% vs 12.1%) and < 6.5% (12.5% vs 1.5%) at EOT (P < .05 for both). Fasting plasma glucose, fasting serum insulin, body weight and homeostatic model assessment of insulin resistance decreased significantly at EOT, in favour of ipragliflozin (adjusted mean difference -1.64 mmol/L, -1.50 µU/mL, -1.72 kg, and -0.99, respectively; P < .05 for all). Adverse event rates were similar between groups (ipragliflozin: 51.4%; placebo: 50.0%). No previously unreported safety concerns were noted. CONCLUSIONS: Ipragliflozin as add-on to metformin and sitagliptin significantly improved glycaemic variables and demonstrated a good safety profile in Korean patients with inadequately controlled T2DM.

Conducting cost-effectiveness analyses of type 2 diabetes in low- and middle-income countries: can locally generated observational study data overcome methodological limitations?

In low- and middle-income countries, the high personal and economic burden of type 2 diabetes is further compounded by inadequate resources for diabetes care when compared with high-income countries. Health technology assessments (HTAs) aim to inform policy decision makers in their efforts to achieve more effective allocation of resources by providing evidence-based input on new technologies. Within the hierarchy of evidence, randomized controlled trials (RCTs) remain the 'gold standard' used to inform HTAs, but are limited by poor external validity (ie, generalizability to real-world populations). Unlike RCTs, observational studies are able to enrol broader patient populations, but their design renders such studies vulnerable to confounding factors and selection bias. However, it is increasingly recognized that observational studies can complement RCTs by supporting and extending efficacy findings from RCTs to real-world clinical practice, particularly across geographical populations. They can also provide locally relevant baseline and disease natural history data to populate health economic models. Thus, observational data are likely to be of considerable informative value to policy makers in developing countries reaching decisions on diabetes care within an environment of scarce resources.

Association of vascular endothelial growth factor polymorphisms with nonproliferative and proliferative diabetic retinopathy.

CONTEXT: Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor, and its polymorphisms are associated with proliferative diabetic retinopathy (PDR) and macular edema. OBJECTIVE: We investigated the contributions of VEGF gene polymorphisms to nonproliferative diabetic retinopathy (NPDR) as well as PDR. DESIGN, SETTING, AND SUBJECTS: In this study we compared VEGF gene variants in a sample of Korean type 2 diabetes patients with and without diabetic retinopathy (DR) and in healthy controls. Of the diabetes patients, 145 had PDR, 108 had NPDR, and 134 had no retinopathy (noDR). They were all duration matched. Samples were genotyped for rs699947, rs1570360, and rs2010963 polymorphisms. RESULTS: We found a significant association between the A allele at rs699947 with DR (odds ratio = 1.84 (95% confidence interval = 1.28-2.66); P = 0.001 vs. noDR). Patients with NPDR, as well as PDR, had increased incidence of the A allele. The AGG haplotype was more frequently found in patients with DR than in patients with noDR (odds ratio = 4.79 (95% confidence interval = 1.42-16.16); P = 0.006). PDR and NPDR patients exhibited an increased incidence of the AGG haplotype. CONCLUSIONS: VEGF polymorphisms might be a useful predictive marker for the development and progression of DR at an earlier stage of diabetes.

[An evaluation of sampling design for estimating an epidemiologic volume of diabetes and for assessing present status of its control in Korea].

OBJECTIVES: An appropriate sampling strategy for estimating an epidemiologic volume of diabetes has been evaluated through a simulation. METHODS: We analyzed about 250 million medical insurance claims data submitted to the Health Insurance Review & Assessment Service with diabetes as principal or subsequent diagnoses, more than or equal to once per year, in 2003. The database was re-constructed to a 'patient-hospital profile' that had 3,676,164 cases, and then to a 'patient profile' that consisted of 2,412,082 observations. The patient profile data was then used to test the validity of a proposed sampling frame and methods of sampling to develop diabetic-related epidemiologic indices. RESULTS: Simulation study showed that a use of a stratified two-stage cluster sampling design with a total sample size of 4,000 will provide an estimate of 57.04% (95% prediction range, 49.83 - 64.24%) for a treatment prescription rate of diabetes. The proposed sampling design consists, at first, stratifying the area of the nation into "metropolitan/city/county" and the types of hospital into "tertiary/secondary/primary/clinic" with a proportion of 5:10:10:75. Hospitals were then randomly selected within the strata as a primary sampling unit, followed by a random selection of patients within the hospitals as a secondly sampling unit. The difference between the estimate and the parameter value was projected to be less than 0.3%. CONCLUSIONS: The sampling scheme proposed will be applied to a subsequent nationwide field survey not only for estimating the epidemiologic volume of diabetes but also for assessing the present status of nationwide diabetes control.