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The aim of this study was to evaluate whether a combination drug therapy that consists of dapagliflozin with three other oral hypoglycemic agents (OHAs) would have a beneficial safety and efficacy profile in T2DM patients who have uncontrolled glucose levels compared to a treatment regimen that contains of basal insulin with two different OHAs.A total of 162 type 2 diabetic patients who are unable to control glucose on their current therapy consisting of 3 OHAs were enrolled in dapagliflozin group and 148 patients in insulin glargine group for the 24-week study period.The mean changes in HbA1c level were comparable as -0.97 ± 1.29% in dapagliflozin group and -0.95 ± 1.41% in insulin glargine group (p = 0.911). Also, the fasting plasma glucose or post-prandial 2 h glucose were comparably decreased in dapagliflozin or insulin glargine. In terms of the body-weight, there was a significant decrease of -2.36 ± 0.51 kg following treatment of dapagliflozin, whereas the increment of 1.93 ± 0.49 kg was in insulin glargine (p 0.001). In terms of adverse events, hypoglycemic events were higher in insulin glargine rather than dapagliflozin (15.1% vs. 1.6%, p 0.05).Our findings demonstrated that the addition of dapagliflozin to an existing drug regimen consisting of three different OHAs in patients exhibiting inadequate blood glucose control could be alternate treatment modality in T2D who hesitate to initiate insulin therapy.

The relative contribution of genetic and clinical factors for bone loss is not well known. This study aimed to investigate the annualized percentage change in total hip bone mineral density (BMD) and the genetic and clinical risk factors for bone loss in a Korean prospective cohort study over a 6-year period.We included 645 men aged ≥50 years and 683 postmenopausal women who had repeated BMD testing between 2007 and 2014. The association between covariates and annualized percentage change in hip BMD was analyzed through the multivariate linear regression analysis. A total of 2614 single-nucleotide polymorphisms (SNPs) from 23 known BMD-related candidate genes and genome-wise association study were investigated.Hip bone loss increased more rapidly in women than in men with advancing age. Hip bone loss in men increased with lean mass (LM) loss (%/year) (P 0.001) and current smoking (P = 0.024) and decreased with increasing waist circumference (WC) (P 0.001), alcohol consumption (P = 0.049), and increase in red blood cell counts (P = 0.031). Decreasing WC (P = 0.009), LM loss (%/year) (P 0.001), and years since menopause ≤ 3 years (P = 0.003) significantly correlated with hip bone loss in women aged 45-59 years. Hip bone loss in women aged ≥60 years increased with advancing age (P = 0.012), alcohol consumption (P = 0.028), LM loss (%/year) (P = 0.031), and fat mass loss (%/year) (P 0.001) and decreased with increasing WC (P = 0.025). LRP5 rs498830 (β = 0.127, P = 0.007) and TNFSF11 rs7325635 (β = 0.146, P = 0.001) were the top SNPs related to hip bone loss in men and postmenopausal women, respectively. However, none of the SNPs were associated with hip bone loss after Benjamini-Hochberg adjustment.In this study, decreasing WC and LM were significant risk factors for hip bone loss in both men and women. Those factors were also identified that had sex-specific or age-specific effects on hip bone loss. None of the SNPs were associated with hip bone loss after multiple testing adjustments. The understanding of the modifiable factors contributing to bone loss has been broadened, and this may have implications such as in developing individualized preventive strategy. Further studies are needed to better predict the risk for bone loss in men and women.

The aim of present study is to compare the efficacy and safety of adding vildagliptin with sulfonylurea dose-increasing as an active comparator in patients who had inadequately controlled type 2 diabetes mellitus (T2DM) using metformin plus sulfonylurea in real clinical practice. Patients using metformin plus sulfonylurea were assigned to either vildagliptin add-on (50 mg twice a day, n=172) or sulfonylurea dose-increasing by 50% (n=172) treatment groups. The primary endpoint was a change in HbA(1c) after 24 weeks. The secondary endpoints were patients achieving HbA(1c)≤7.0% (53 mmol/mol) and changes in the fasting plasma glucose (FPG), 2-h postprandial glucose (2pp), lipid profiles, and urine albumin-to-creatinine ratio. Body weight and hypoglycemia were also investigated. The mean HbA(1c) at baseline was 8.6% (70 mmol/mol) in both groups. At week 24, the adjusted mean HbA(1c) levels decreased by -1.19% (-13.09 mmol/mol) with vildagliptin add-on and -0.46% (-5.06 mmol/mol) with sulfonylurea (P0.001). Significantly more vildagliptin add-on patients achieved HbA(1c)≤7.0% (53 mmol/mol) than did sulfonylurea patients (40.1% vs. 7.9%; P0.001). Greater reductions in FPG and 2pp were observed with vildagliptin add-on than with sulfonylurea (P0.001). The vildagliptin add-on group exhibited no clinically relevant weight gain and had a lower incidence of hypoglycemia compared with the sulfonylurea group. Vildagliptin add-on therapy might be a suitable option for patients with T2DM that is controlled inadequately by metformin and sulfonylurea, based on its greater glucose control and better safety profile (ClinicalTrial.gov: NCT01099137).

The clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes.We recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3-6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7-6.4%, 39-46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated.Eighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥ 165 mg/dL and a 30-min C-peptide5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98-26.16) of developing diabetes than other prediabetic subjects.In Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population.