Effectiveness and Safety of Evogliptin in Patients With Type 2 Diabetes Mellitus: A Multicenter, Prospective, Observational Study.

Changes in HbA1c levels and body mass index after successful decompression surgery in patients with type 2 diabetes mellitus and lumbar spinal stenosis: results of a 2-year follow-up study

Prescriptions of SGLT2 inhibitors (SGLT2i) for patients with type 2 diabetes (T2DM) are increasing. In this study real-world data were used to evaluate the long-term benefits of SGLT2i as a second-line drug for glycemic control in people with T2DM being treated with DPP-4 inhibitor (DPP4i) or metformin (MET) monotherapy. People with T2DM patients on DPP4i or MET monotherapy were followed for at least 12 months after receiving a new SGLT2i prescription. Patients were divided into DPP4i and MET groups, and patient background factors were controlled for using propensity score matching (PM). Changes in HbA1c and other indexes during the 12 months after the new prescription were compared using t-tests, and the factors affecting changes in HbA1c were examined using multiple regression analysis. After PM, there were 192 patients in the DPP4i (n=96) and MET (n=96) groups, with no significant differences in patient backgrounds. HbA1c levels 12 months after a new SGLT2i prescription were significantly lower in both groups compared to base line (8.1% to 7.0%, p<0.001; 8.1% to 7.1%, p<0.001), but there were no significant differences between the two groups in the change in HbA1c level (p=0.271), body weight (p=0.371), systolic blood pressure (p=0.828), eGFR (p=0.642), and Fib-4 index (p=0.674). The change in HbA1c was greater for those with initially higher HbA1c levels (-0.629 [-0.722-0.536], p<0.001) and those with shorter diabetes histories (0.024 [0.001-0.048], p=0.044), but it was not significantly different between the two groups (p=0.236). After controlling for patient background, there was no significant difference in the long-term effects of a new SGLT2i prescription between those previously receiving either DPP4i or MET monotherapy, but higher previous HbA1c levels and a shorter diabetes history may be prediction of better HbA1c 12 months after a new SGLT2i prescription, regardless of prior medication. Disclosure H.Takahashi: Speaker's Bureau; Eli Lilly Japan K.K., Boehringer Ingelheim Japan, Inc., Medtronic, Novo Nordisk. Y.Suganuma: None. T.Ohno: None. R.Nishimura: Speaker's Bureau; Sanofi K.K., Medicure Inc., Boehringer Ingelheim Inc., Takeda Pharmaceutical Company Limited, Kissei Pharmaceutical Co., Ltd., Novartis Pharma K.K., Eli Lilly Japan K.K., Novo Nordisk, Merck & Co., Inc., Abbott Japan Co., Ltd., Astellas Pharma Inc., Teijin Pharma Limited, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., AstraZeneca.

Aims. The aim of this study is to examine the efficacy of adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to patients with type 2 diabetes inadequately controlled by metformin and sulphonylurea combination treatment. The response of Asian and non-Asian patients to this regimen was also examined. Methods. The medical and computerized records of 80 patients were examined. These patients had baseline HbA1c levels ranging from 7.0 to 12.5% and had a DPP-4 inhibitor add-on therapy for a minimum period of 12 weeks. The primary endpoint was the change in HbA1c level before and after DPP-4 inhibitor treatment. Results. During oral triple therapy, there was a reduction of HbA1c from 8.3% (7.7–8.9) to 7.2% (6.8–7.6) and 26 patients (32.5%) achieved an HbA1c <7%. Poor baseline glycaemic control, lower BMI, and younger age were associated with a better response, but duration of diabetes and gender did not affect outcome. The HbA1c reduction was not different between Asians and non-Asians group [−1.00% (0.6–1.3) vs −0.90% (0.4–1.6)]. Conclusions. DPP-4 inhibitor as a third-line add-on therapy can achieve significant glycaemic improvement in patients with type 2 diabetes inadequately controlled on the combination of metformin and sulphonylurea. The improvement in HbA1c was similar between Asian and non-Asian patients.

ObjectiveThe objective of this study is to elucidate the effect of anagliptin on glucose/lipid metabolism and renoprotection in patients with type 2 diabetic nephropathy.MethodsTwenty-five patients with type 2 diabetic nephropathy...

To investigate the effects of the interaction between glycated haemoglobin (HbA1c) genetic risk score and weight changes during and after pregnancy (postpartum weight reduction and gestational weight gain) on long-term glycaemic changes in the largest cohort of women with a history of gestational diabetes mellitus (GDM). This was a retrospective cohort using the baseline data from the Tianjin Gestational Diabetes Mellitus Prevention Programme. A genetic risk score was established by combining 10 HbA1c-related single-nucleotide polymorphisms, which were identified by genome-wide association studies. General linear regression models were applied to evaluate the effect of interaction between HbA1c genetic risk score and weight changes during and after pregnancy (postpartum weight reduction and gestational weight gain) on glycaemic changes. 'A total of 1156 women with a history of GDM were included in this respective cohort study. Statistical differences in pre-pregnancy weight, pre-delivery weight and postpartum weight were evidenced across different groups of postpartum weight reduction. After adjusting for covariates, statistical significance for changes in HbA1c level was only observed in the postpartum weight reduction <5 kg/y group (P = 0.002), and a significant effect of interaction between HbA1c genetic risk score and postpartum weight reduction on long-term changes in HbA1c was evidenced (P interaction = 0.01). In women with postpartum weight reduction ≥8 kg/y, those with a lower HbA1c genetic risk score had a greater decrease in HbA1c level. HbA1c genetic risk score interacts with postpartum weight reduction to affect long-term changes in HbA1c levels among women with a history of GDM.

Effects of linagliptin monotherapy compared with voglibose on postprandial blood glucose responses in Japanese patients with type 2 diabetes: Linagliptin Study of Effects on Postprandial blood glucose (L-STEP)

There is no definitive evidence as to whether oral hypoglycemic agents (OHA) should be continued or withdrawn prior to the introduction of insulin therapy on an outpatient basis. Insulin Lispro Mixture-50 (LM-50), which supplements basal insulin secretion because of the presence of the intermediate-acting component contained in it, may enable more stable glucose control and allow discontinuation of prolonged OHA therapy, such as with sulfonylureas (SU). To determine whether the introduction of three times daily (t.i.d.) injections of LM-50 on an outpatient basis was effective in yielding adequate glucose control in patients with type 2 diabetes (T2D) who had poor glucose control despite treatment with OHA, patients were divided into two groups: those in whom the use of all OHA except SU was suspended [the SU(+) group; n = 10] and those in whom all OHA, including SU, were discontinued [the SU(−) group; n = 12]. Twenty-two patients with T2D undergoing treatment at Saiseikai Niigata Second Hospital were included in the study. Patients had been treated with maximum doses of OHA, but had failed to show adequate glucose control (HbA1c ≥7%). All patients refused inpatient therapy, but agreed to receive LM-50 injections t.i.d. on an outpatient basis. All patients provided informed consent for inclusion in the present study, which was an open-label, randomized, active-controlled, parallel-group, comparative study. For patients in the SU(+) group, SU was continued at the same dose and LM-50 injections were started at a dose of 0.1 units/kg, t.i.d. Patients in the SU(−) group were started on the same dose of LM-50, but all OHAs were discontinued. The primary efficacy endpoint was the change in HbA1c level. After 1–2 months of LM-50 injections, patients began to get used to the self-monitoring of blood glucose levels and the dose of LM-50 injected was adjusted with the aim of reducing preprandial blood glucose levels to ≤130 mg/dL. Changes in HbA1c levels for patients in both the SU(+) and SU(−) groups are shown in Fig. 1. For the 10 patients in the SU(+) group, significant decreases in HbAlc started to be seen after 1 months treatment with LM-50. Similarly, patients in the SU(−) group exhibited significant decreases after 1 months treatment with LM-50. At the end of 12 months, significant improvements were observed in both the SU(+) and SU(−) groups, with the effects of LM-50 t.i.d. almost the same, regardless of whether SU was continued or discontinued. In the SU(+) group, the percentage of patients in whom HbA1c fell to <7.0% or <6.5% was 50% and 20%, respectively, compared with 66.7% and 41.7%, respectively, in the SU(−) group. There was no significant difference in the percentage change in HbA1c or the percentage of patients in whom HbA1c fell to <7.0% and <6.5% between the two groups. Mean HbA1c levels in patients in whom the use of all oral hypoglycemic agents (OHA), except sulfonylureas (SU), was suspended [SU(+) group; n = 10; ◆] and those in whom all OHA, including SU, were discontinued [SU(−) group; n = 12; ]. The decrease in HbA1c levels at each time point was significantly different compared with baseline levels (Month 0) in both groups. Data are the mean ± SD. *P < 0.05, **P < 0.01 compared with baseline. The body mass index (BMI) and insulin dose administered increased significantly in both the SU(+) and SU(−) groups over the 12-month treatment period (Table 1). There were no significant differences in terms of the percentage change in BMI or the insulin dose between the two groups (Table 1). Furthermore, although the incidence of slight hypoglycemia was the same in the SU(+) and SU(−) groups, serious hypoglycemia did not occur in any of the patients in either group during the 12-month observation period. In general, it is believed that when insulin therapy is introduced on an outpatient basis, complete discontinuation of SU treatment often results in a decrease in the amount of insulin that enters the portal vein, thereby exacerbating hyperglycemia. However, this scenario was not observed in the present study, probably because the LM-50 used in the present study contained both an ultraquick-acting component and an intermediate-acting component (in a ratio of 1:1) and the intermediate-acting component acted in lieu of the basal secretory component induced by SU treatment. Because the LM-50 used in the present study contains bolus insulin and basal insulin at a ratio of 1:1, it is believed that this provides insulin in a pattern that approximates physiological secretion in humans.1, 2 In conclusion, LM-50 injections administered three times daily produced almost the same effects in patients with initially poor glycemic control on OAH, regardless of whether SU was continued. The authors declare that there are no conflicts of financial interest in terms of the information contained in this paper.

Vitamin D endocrine system is a potential immune system modulator and has been implicated in the pathogenesis of several autoimmune diseases including Type 1 Diabetes Mellitus (T1DM). Studies have demonstrated an inverse risk relationship between T1DM and Vitamin D levels and also, shown a reduced risk of the disease with its supplementation. To evaluate the role of Vitamin D as an adjuvant in improving glycaemic control and residual pancreatic beta-cell function. Primary outcome was the mean change in HbA1c levels over a period of six months. This double-blinded randomized controlled trial was done in a tertiary care hospital, Southern India and included 52 children aged 1-18 years with T1DM, with 26 participants each in the intervention and standard of care arm. Oral Vitamin D therapy was administered once a month for six months in addition to insulin in intervention arm while only insulin was continued for other arm. Plasma HbA1c, serum 25-Hydroxy vitamin D (25OHD), insulin dose and C-peptide were measured at baseline and repeated after 6 months. Prevalence of Vitamin D deficiency was as high as 63.5% i.e., 33 of total 52 children with T1DM. The mean C-peptide levels were significantly high in intervention arm as compared to standard of care after six months. However, there was no significant difference in HbA1c, and insulin requirement at six months between the two groups. No adverse events due to Vitamin D therapy were noted. Oral Vitamin D may serve as an adjuvant to insulin therapy for children with T1DM by augmenting residual beta-cell function and improving insulin secretion. However, a significant decrease in HbA1c level and requirement for exogenous insulin was not achieved in our study.

ObjectiveTo compare the efficacy and safety of an initial triple therapy using metformin, a dipeptidyl peptidase-4 (DPP4) inhibitor, and thiazolidinedione with a stepwise approach using sulfonylurea and metformin in new-onset,...

Objectives: To directly compare the long-term effectiveness and durability of sodium glucose co-transporter 2 (SGLT2) inhibitor, an empagliflozin-based quadruple therapy and insulin glargine-based therapy in patients with poorly controlled type 2 diabetes (T2D). Research Design and Methods: Eligibility for this 3-year, open-label, prospective observational study was T2D patients (HbA1c, 7.5 - 12.0%) despite three distinct OADs (metformin, 2000 mg/day; dipeptidyl peptidase-4 inhibitor, maximal dose; and glimepiride ≥6 mg/day) between January 2017 and December 2021. Empagliflozin (25 mg/day, n = 167) or insulin glargine (n = 166) was added as the next agent. Outcomes included the time-to-treatment adjustment, changes in HbA1c level, and safety. Propensity score matched comparison and Kaplan-Meier estimation analysis were used. Results: The estimated median time to treatment adjustment for empagliflozin group was 36.1 months (95% confidential interval [CI], 31.1 - 41.2), which was significantly longer than 18.3 months for the insulin glargine-based therapy (95% CI, 14.5 - 22.0). The mean change in HbA1c from baseline to month 36 were -1.5±1.0% and -1.0±1.4% in the empagliflozin group and the insulin glargine group, respectively (P=0.043). FPG showed a similar trend, although there was no statistical significance (-61.3±54.5 mg/dL vs -4.0±97.5 mg/dL, empagliflozin and insulin glargine group, respectively, P=0.129). Body weight showed a significant decrease in the empagliflozin group (-3.1±3.7 kg, P=0.003), whereas a significant increase in the insulin glargine group (3.2±2.6 kg, P&amp;lt;0.001). Conclusions: This study demonstrated that the effectiveness of empagliflozin as a quadruple combination therapy has been sustained for 3 years. In general, empagliflozin treatment was better than insulin glargine-based combination therapy. Disclosure E.Ku: None. T.Oh: None.

Background &#13;\nTelehealth is a communication technology that allows exchange of data between patients and health care providers. Disease management is a structured multifaceted intervention to patient care that promotes self-management skills and improves patient-doctor communication. This systematic review aims to determine the effectiveness of “telehealth diabetes management programmes” for patients with type-2 diabetes (T2DM) in improving outcomes such as glycaemic control, diabetes related mortality, hospital admissions and overall cost-effectiveness of programme. Its applicability to Hong Kong will be reviewed.&#13;\n&#13;\nMethods&#13;\nA literature search of electronic bibliographic databases was performed to identify relevant articles. Both randomised control trials and observational studies on patients with T2DM published up to March 2013 were included in the analysis.&#13;\n&#13;\nResults &#13;\nA total of 14 articles were eligible (n=9708 subjects). Eight were randomised controlled trials and six observational studies. Ten studies reported on mean change in HbA1c level, three on health care utilization and three on cost-effectiveness of telehealth management programme. No studies had diabetes related mortality as their outcome measure. Across these trials, telehealth diabetes management programme resulted in an improvement in glycaemic control, likely reduction in health service utilization and a probable cost-effective programme.&#13;\n&#13;\nDiscussions &#13;\nThe current Hong Kong’s health care system faces challenges from long wait-list for medical consultations and rising health care costs. The applicability of the results from this review to the setting in Hong Kong, and feasibility of implementation will be discussed.&#13;\n&#13;\nConclusion &#13;\nTelehealth disease management programmes had clinically modest but significant improvement in HbA1c among adults with T2DM and likely to be cost-effective. The results of this review have potential important implications for policy makers in the allocation of health care resources.

Optimal glycemic control in type 2 diabetes (T2D) remains an elusive goal despite an expanding range of effective treatments and technologies. Sustained, disciplined adherence to lifestyle modifications leads to positive outcomes in T2D, although converting medical recommendations into effective patient action is challenging in real-world practice. The emergence of AI and machine learning (ML) presents innovative opportunities to prompt effective lifestyle modifications and diabetes goal achievements in highly user-specific and user-friendly ways. The Twin Precision Treatment system is an AI-enabled bundled system of sensors and coaching that generates personalized recommendations through wearable Bluetooth-enabled technologies (including continuous glucose monitors), targeted laboratory data, Internet of Things, AI-ML algorithms, and human input. The authors designed a study to explore whether or not this bundled system intervention (INT) could help individuals — with T2D and managed in a primary care setting — achieve glycemic targets while concurrently de-escalating glucose-lowering medications. This single-center trial randomly assigned 150 adults with T2D and a body mass index (the weight in kilograms divided by the square of the height in meters) ≥27 to the INT (N=100) or a usual care (UC) control group (N=50). The primary end point was a hemoglobin A1c level (HbA1c) <6.5% (<48 mmol/mol; “target”) without glucose-lowering medications, except metformin, at 12 months; a secondary end point was the same outcome sustained for ≥90 days prior to 12 months. Other secondary end points included target attainment without any glucose-lowering medications at 12 months and ≥90 days prior to 12 months, as well as HbA1c and weight changes at 12 months. The primary end point was achieved by 71.0% (95% confidence interval [CI], 60.1 to 80.0) of INT participants versus 2.4% (95% CI, 0.5 to 11.6) of UC participants (P<0.001). Significantly more INT participants than UC participants achieved or sustained target ≥90 days prior to 12 months without glucose-lowering medications, except metformin (52.5% vs. 2.8%; P<0.001). The mean changes in HbA1c levels (−1.3% vs. −0.3%; P<0.001) and body weight (−8.6% vs. −4.6%; P<0.001) were significantly greater in the INT group than in the UC group. Other secondary end points were not significantly different. In post hoc analysis, overall use of glucose-lowering pharmacotherapy decreased markedly in the INT group but not the UC group. Quality-of-life and treatment satisfaction scores improved significantly from baseline in the INT group but not in the UC group (exploratory analyses). Overall, the AI-enabled bundled system of sensors and coaching facilitated significant improvements in glycemic control, weight loss, and quality of life versus UC, while allowing marked de-escalation of glucose-lowering pharmacotherapy.

Predictors for the effect of sodium glucose co-transporter 2 (SGLT2) inhibitors at lowering hemoglobin A1c (HbA1c) levels in type 2 diabetes mellitus patients remain unclear. We therefore aimed to elucidate these predictors in type 2 diabetes patients after 3months of SGLT2 treatment. A total of 302 consecutive type 2 diabetes patients who had been treated with SGLT2 inhibitors as monotherapy or add-on therapy to existing antidiabetic treatments were enrolled retrospectively. After excluding 27 patients whose HbA1c levels could not be evaluated 3months after treatment, the glucose-lowering effects of SGLT2 inhibitors were assessed in 275 patients by measuring HbA1c levels before and 3months after treatment. The predictors for changes in HbA1c levels after 3months of treatment were evaluated. SGLT2 inhibitor treatment for 3months decreased HbA1c levels from 7.8±1.2% to 7.4±1.0% (p<0.0001). A multiple regression analysis showed that the independent determinants for SGLT2 inhibitor treatment effect included decreased HbA1c levels after 1month of treatment, high baseline HbA1c levels, and a high estimated glomerular filtration rate (eGFR). We show that type 2 diabetes patients who received the greatest glucose-lowering effect with SGLT2 inhibitor treatment were those with preserved renal function (high baseline eGFR) and high baseline HbA1c levels. Moreover, SGLT2 inhibitor treatment efficacy could be predicted by the patients' initial response to treatment.

The indirect impact of the COVID-19 pandemic on people with type 2 diabetes mellitus and without COVID-19 infection: Systematic review and meta-analysis

Optimal insulin titration is essential in helping people with type 2 diabetes mellitus (T2DM) to achieve adequate glycemic control. Barriers of people with diabetes to implementation of titration include lack of self-efficiency and self-management skills, increased diabetes-related distress, low treatment satisfaction, poor well-being, as well as concerns about hypoglycemia and insulin overdose. My Dose Coach is a digital health tool for optimizing titration of basal insulin that combines a smartphone app for patients with T2DM and a Web portal for healthcare professionals. This is a prospective, open-label, multicenter, randomized controlled parallel study conducted in approximately 50 centers in Germany that are specialized in the treatment of diabetes. Patients in the intervention group will use the titration app and will be registered on the Web portal by their treating physician. Control group patients will continue their current basal insulin titration without using the app. The primary outcome is the mean change in HbA1c levels at the 12-week follow-up. The secondary outcome measures include patient-reported outcomes such as diabetes-related distress, self-management, empowerment, self-efficacy, treatment satisfaction, and psychological well-being as well as fasting blood glucose values. This digital health tool has been previously implemented in several independent pilot studies. The findings from this multicenter randomized controlled trial can provide further evidence supporting the effectiveness of this tool in patients with T2DM and serve as a basis for its clinical integration. German Register for Clinical Studies-DRKS-ID: DRKS00024861.