Other Oral Antidiabetic Drugs Research Articles

Effectiveness of Dapagliflozin as Add-On to Metformin with or without Other Oral Antidiabetic Drugs in Type 2 Diabetes Mellitus: A Multicentre, Retrospective, Real-World Database Study.

Real-world Indian studies evaluating effectiveness of dapagliflozin as an add-on to other oral antidiabetic drugs (OAD) in patients with type 2 diabetes mellitus (DM) are scarce. An electronic medical record (EMR)-based, retrospective, multicentre study was conducted to evaluate the effectiveness of dapagliflozin as add-on therapy in adult patients with inadequately controlled DM on metformin with or without other OAD. Baseline characteristics (visit 1: metformin or metformin plus OAD treatment for at least 30 days) and treatment-related outcomes (visit 2: follow-up) considered between 60 and 140 days after adding/switching dapagliflozin [glycated haemoglobin (HbA1c), body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP)] were analysed. A total of 3616 patients were screened from 478 centres. Most patients had received dapagliflozin(D)+metformin(M)+at least one other OAD [D+M+OAD, n=2907 (80.4%), 408 followed-up with HbA1c reported], while 709 patients (19.6%, 138 followed-up with HbA1c reported) received dapagliflozin+metformin (D + M). Treatment with dapagliflozin as an add-on therapy resulted in significant change in HbA1c (-1.1 ± 1.44%; p < 0.05 for HbA1c subgroup ≥7.5%; -1.6±1.41%; p < 0.05 for HbA1c subgroup ≥8%) at visit 2 compared with visit 1. Significant change in body weight (-1.4±3.31 kg; p < 0.05 for HbA1c subgroup ≥7.5%; -1.5±3.22kg; p < 0.05 for HbA1c subgroup ≥8%) was observed at visit 2. Similarly, a significant change in BMI was noted for the HbA1c subgroup ≥7.5% (-1.0±8.38 kg/m2). However, the change in BMI in the HbA1c subgroup ≥8% was noted to be -1.4±10.4 kg/m2, which was not statistically significant (p=0.08). In the overall study population, significant change in the SBP (-4.5±14.9mmHg; p < 0.05 for HbA1c subgroup ≥7.5%; -4.5±15.1 mmHg; p < 0.0001 for HbA1c subgroup ≥8%) was observed at visit 2 compared with visit 1. On identical lines, significant change in DBP (-1.5±8.94 mmHg; p < 0.05 for HbA1c subgroup ≥7.5%; -1.4±8.91mmHg; p < 0.05 for HbA1c subgroup ≥8%) was noted. Dapagliflozin showed significant improvement in glycemic parameter, BMI and BP when added to metformin, with or without other OADs in a real-world scenario.

Effect of dipeptidyl peptidase-4 inhibitors on postprandial glucagon level in patients with type 2 diabetes mellitus: A systemic review and meta-analysis.

AimsHyperglucagonemia occurs in the pathogenesis of type 2 diabetes mellitus (T2DM). In this meta-analysis, we summarized the effects of DPP4 inhibitors on glucagon levels in patients with T2DM.Materials and methodsRandomized controlled trials (RCTs) comparing the influence of DPP4 inhibitors on circulating glucagon levels with placebo or other oral antidiabetic drugs (OADs) in patients with T2DM were identified by searches of Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library). Only studies reporting changes in glucagon level presented as total area under the curve (AUCglucagon) using a meal or oral glucose tolerance test were included. Results were combined using a random-effects model that incorporated potential heterogeneity among the included studies.ResultsA total of 36 RCTs with moderate to high quality were included. Overall, the numbers of T2DM patients included for the meta-analyses comparing DPP4 inhibitors with placebo and other OADs were 4266 and 1652, respectively. Compared to placebo, DPP4 inhibitors significantly reduced circulating glucagon levels (standard mean difference [SMD]: -0.32, 95% CI: -0.40 to -0.24, P<0.001; I2 = 28%). Analysis of subgroups revealed that study characteristics had no significant effect on results, such as study design (parallel group or crossover), number of patients, mean patient age, proportion of men, baseline HbA1c, duration of diabetes, background therapy, treatment duration, or methods for glucagon measurement (all P for subgroup differences >0.05). Moreover, DPP4 inhibitors significantly reduced glucagon levels compared to other OADs (SMD: -0.35, 95% CI: -0.53 to -0.16, P<0.001; I2 = 66%), and the reduction in glucagon was greater in comparison with insulin secretagogues than in comparison with non-insulin secretagogues (P for subgroup difference =0.03).Systematic review registration https://inplasy.com/, identifier INPLASY202280104.ConclusionsDPP4 inhibitors are effective at reducing the circulating postprandial glucagon level in T2DM patients.

Influence of dipeptidyl peptidase-4 inhibitors on glycemic variability in patients with type 2 diabetes: A meta-analysis of randomized controlled trials.

ObjectiveThe influence of dipeptidyl peptidase-4 (DPP4) inhibitors on glycemic variability compared to other oral antidiabetic drugs (OADs), measured based on the mean amplitude of glycemic excursions (MAGE), has not been comprehensively analyzed. The aim of the study was to perform a meta-analysis to compare the effects of DPP4 inhibitors on MAGE with other OADs in type 2 diabetes mellitus (T2DM) patients without concurrent insulin treatments.MethodsThe Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library) databases were searched for relevant randomized controlled trials (RCTs). Study characteristics and outcome data were independently extracted by two authors. A random-effect model was used to combine the results.ResultsFourteen studies with 855 patients were included. Compared to other OADs, DPP4 inhibitors significantly reduced MAGE (mean difference [MD]: -0.69 mmol/L, 95% confidence interval [CI]: -0.95 to -0.43, P<0.001) with mild heterogeneity (I2 = 28%). Predefined subgroup analyses suggested that DPP4 inhibitors were more effective in reducing MAGE compared to insulin secretagogues (MD: -0.92 mmol/L, P<0.001) and non-secretagogues (MD: -0.43 mmol/L, P=0.02), as well as compared to sulfonylureas (MD: -0.91 mmol/L, P<0.001) and sodium glucose cotransporter 2 inhibitors (MD: -0.67 mmol/L, P=0.03).ConclusionsDPP4 inhibitors may significantly reduce glycemic variability compared to other oral anti-diabetic drugs, as evidenced by MAGE in T2DM patients with no concurrent insulin treatment.Systematic review registrationINPLASY, registration number: INPLASY2021120113.

Efficacy and Safety of Metformin Versus the Other Oral Antidiabetic Drugs in Japanese Type 2 Diabetes Patients: A Network Meta-analysis.

IntroductionAlthough metformin is recommended as a first-line treatment for patients with type 2 diabetes (T2D) in Western countries, no specific treatment is recommended in Japan, and various agents are used. Metformin has long been used at low doses in Japan, and information regarding its effect at the maximum maintenance dose is lacking. Here, we compared the efficacy and safety of metformin at 1500 mg/day with those of the other oral anti-diabetic drugs (OADs) approved in Japan.MethodsRandomized controlled trials comparing a change in hemoglobin A1c (HbA1c) from baseline at 12 weeks or later (ΔHbA1c) among OADs (including placebo) as a first-line treatment in adult patients with T2D were selected by systematic review with comprehensive searching of CENTRAL, MEDLINE, Ichushi Web, and EMBASE and manual searching of clinical trial registries. The ΔHbA1c and incidence of hypoglycemia were compared among OAD treatments using Bayesian network meta-analysis (NMA). The relative risk (RR) of the incidence of hypoglycemia was determined relative to that of placebo.ResultsForty-six randomized controlled trials were identified in the systematic review, and 37 studies, comprising 38 different types of treatments, including placebos, were selected for the NMA of ΔHbA1c. Compared with metformin 1500 mg/day, 20 OAD treatments were significantly less effective in reducing HbA1c from baseline (differences from metformin 1500 mg/day: 0.40–0.96%). Two treatments (glimepiride 2 mg/day and pioglitazone 45 mg/day) showed greater mean reductions in HbA1c from baseline than metformin 1500 mg/day (− 0.38% and − 0.03%), although these differences were not significant. Regarding the incidence of hypoglycemia, only pioglitazone 30 mg/day among 31 treatments showed a lower RR (< − 0.01), whereas 23 treatments showed a significantly higher RR (1.02–66.71) than metformin 1500 mg/day.ConclusionThe NMA suggested a preferable efficacy and safety profile of metformin 1500 mg/day compared with the other OADs approved in Japan.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01979-1.

Antidiabetic effect of gemigliptin: a systematic review and meta-analysis of randomized controlled trials with Bayesian inference through a quality management system

Gemigliptin is one of the latest dipeptidyl peptidase-4 inhibitors developed by LG Life Sciences. Since the early 2000s, several randomized controlled trials (RCTs) of gemigliptin have been conducted. However, no study has directly compared its antidiabetic effects through a systematic review and meta-analysis. Therefore, in this study, we performed a systematic review and meta-analysis on RCTs. In particular, a subsequent meta-analysis was performed using Bayesian inference, and an updated quality management system model was integrated throughout our study. The mean differences and 95% confidence intervals for glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), homeostatic model assessment beta cell function (HOMA-β), and low-density lipoprotein (LDL) were evaluated for the efficacy outcomes of gemigliptin as compared to those of placebo and other oral antidiabetic drugs (OADs). In conclusion, we found that gemigliptin was superior to placebo and comparable to other OADs in terms of the effect on HbA1c, FPG, HOMA-β, and LDL. Further, gemigliptin was more effective than other OADs in HbA1c and HOMA-β in Bayesian inference analysis and statistically significant to other OADs in HbA1c and HOMA-β in sensitivity analysis excluding metformin. However, to confirm the results, more studies need to be analysed and the minimum clinically important difference must be applied.

DUAL II China: Superior HbA1c reductions and weight loss with insulin degludec/liraglutide (IDegLira) versus insulin degludec in a randomized trial of Chinese people with type 2 diabetes inadequately controlled on basal insulin.

AimTo assess the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin degludec (degludec) in Chinese people with type 2 diabetes (T2D) treated with basal insulin.Materials and MethodsIn DUAL II China, a randomized, double‐blinded, multicentre, treat‐to‐target trial, Chinese adults with T2D and HbA1c of 7.5% or more on basal insulin and metformin, with or without other oral antidiabetic drugs (OADs), were randomized 2:1 to 26 weeks of treatment with either IDegLira (max. dose 50 U degludec/1.8 mg liraglutide) or degludec (max. 50 U/day), respectively, combined with metformin. At 26 weeks, superiority of IDegLira over degludec was assessed for change in HbA1c (primary endpoint), and body weight and number of severe or blood glucose (BG)‐confirmed hypoglycaemic episodes (confirmatory secondary endpoints).ResultsOverall, 453 participants were randomized to IDegLira (n = 302) or degludec (n = 151). Superiority was confirmed for IDegLira over degludec in HbA1c change (−1.9% vs. −1.0%, respectively, estimated treatment difference [ETD] [95% confidence interval]: −0.92% [−1.09; −0.75], P < .0001), body weight change (−0.7 vs. +0.4 kg, respectively, ETD [95% CI]: −1.08 kg [−1.63; −0.52], P = .0002) and severe or BG‐confirmed hypoglycaemia (estimated rate ratio [95% CI]: 0.53 [0.30; 0.94], P = .0297). The odds of achieving HbA1c less than 7.0% without hypoglycaemia and/or weight gain were greater with IDegLira than degludec (P < .0001 for all). Daily insulin dose at 26 weeks was lower for IDegLira (34.3 U) than degludec (37.4 U) (P = .0014). No unexpected safety signals were observed.ConclusionsIDegLira may be an efficacious and well‐tolerated treatment intensification option for Chinese people with T2D uncontrolled on basal insulin and OADs.

Sodium-Glucose Cotransporter-2 Inhibitors Ameliorate Liver Enzyme Abnormalities in Korean Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are reported to reduce body fat in patients with type 2 diabetes mellitus (T2DM), and SGLT2i-induced weight reduction may help improve comorbid nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the potential benefit of SGLT2is over other oral antidiabetic drugs (OADs) in patients with T2DM-associated NAFLD. We enrolled real-world Korean patients with T2DM-associated NAFLD in whom initial metformin therapy had been modified by stepwise addition of OAD(s) due to insufficient glucose control. Propensity score (PS) matching was used for the comparison of changes in clinical and biochemical parameters to balance potential covariates. Among the 765 enrolled patients, 663 patients received additional OADs other than SGLT2i and 102 patients received SGLT2i therapy. PS matching selected 150 and 100 patients from the control and the SGLT2i group, respectively. The SGLT2i group lost more weight than the control group at 6 months (mean –1.3 kg vs. 0.0 kg; P < 0.001). Alanine aminotransferase (ALT) levels also decreased more in the SGLT2i group at 3 (–11 U/L vs. –1 U/L), 6 (–12 U/L vs. –1 U/L), and 12 months (–14 U/L vs. –2 U/L) (all P < 0.05). Addition of SGLT2is was an independent predictor of ALT improvement in a multivariate logistic regression model (odds ratio 1.91; P = 0.016). Compared with other OADs, addition of SGLT2is was more effective in weight reduction and ALT improvement in patients with T2DM and comorbid NAFLD.

EMPAGLIFLOZIN IS MORE EFFECTIVE IN REDUCING MICROALBUMINURIA AND ALT LEVELS COMPARED WITH DAPAGLIFLOZIN: REAL LIFE EXPERIENCE.

Sodium Glucose Co-Transporter-2 inhibitors (SGLT2i) are oral antidiabetic agents that can be used with insulin in the treatment of type 2 diabetes mellitus, known for cardiovascular and renal benefits. Dapagliflozin and empagliflozin are available in Turkey and we aimed to evaluate real-life data of using these two molecules with other oral antidiabetic drugs (OAD) or insulin. 119 patients (59 women, 60 men) files who had started SGLT2i between 2017-2019 were examined retrospectively until 6 months after the treatment change. Patients' weight, body mass index (BMI), insulin doses, fasting blood glucose, HbA1c, lipid profile, spot urine albumin/creatinine ratio, e-GFR values, ALT, AST, uric acid levels were evaluated at baseline, 3 months and 6 months. 41.2% of patients were using dapagliflozin and 58.8% were using empagliflozin. After 6 months of follow-up, HbA1c decreased from 8.27% to 7.45% (p<0.001). Daily total insulin dose decreased from 84.75 to 75.58 U/day in 3 months (p<0.004). Weight and BMI decreased significantly at 6 months. ALT, AST decreased significantly in patients using insulin (p 0.001 and 0.007), whereas spot urine microalbumin/creatinine ratio decreased at 3 and 6 months (p 0.005 and 0.020). A significant decrease was also observed in uric acid levels (p: 0.026). Dapagliflozin and empagliflozin have beneficial effects on decreasing glycemic parameters, weight, transaminases, uric acid and microalbuminuria in the real life environment. We also observed that SGLT2i and insulin combination is as safe and effective as combination with OAD.

Real-World Effectiveness of Sodium Glucose Co-Transporter-2 Inhibitors in Japanese Patients with Diabetes Mellitus.

IntroductionSodium glucose co-transporter-2 inhibitors (SGLT2i) have been on the market for 5 years in Japan. We explored the real-world effectiveness of SGLT2i in Japan.MethodsWe retrospectively analyzed two large Japanese administrative databases from JMDC Inc.: insurance-dataset (I-dataset) and Medical Data Vision Co. Ltd. [hospital-dataset (H-dataset)]. Patients who newly started SGLT2i or other oral antidiabetic drugs (OADs) between 1 April 2014 and 31 March 2016 were selected for this analysis and followed for 1 year from the index date. Changes in glycated hemoglobin (HbA1c), body mass index (BMI), and estimated glomerular filtration rate (eGFR) were evaluated during the 1-year period.ResultsA total of 127,961 patients in the H-dataset and 26,436 in the I-dataset were included in this analysis. Baseline HbA1c, BMI, and eGFR levels tended to be higher in SGLT2i users than in other OAD cohorts. After 1 year, 44.3% (I-dataset) and 53.3% (H-dataset) of SGLT2i users and 33.0–44.2% (I-dataset) and 47.0–58.1% (H-dataset) of other users were still on their medications. The mean HbA1c level decreased by − 0.7 to − 0.9% in SGLT2i users versus − 0.4 to − 1.5% in the other cohorts. The mean BMI decreased by − 0.8 kg/m2 in SGLT2i users whereas the change in other cohorts was − 0.5 to 0.4 kg/m2. No clinically relevant changes in eGFR were observed over the period.ConclusionThis study showed that around half of the SGLT2i users were still on medication after 1 year from treatment initiation. Initiation of SGLT2i was associated with improvement in HbA1c and BMI, with no abnormal changes in renal function observed in the first year following treatment. These findings support the results from clinical trials and will expand the existing evidence of SGLT2i use in real-life practice in Japan.FundingAstellas Pharma Inc., Tokyo, Japan.Electronic supplementary materialThe online version of this article (10.1007/s13300-019-00708-w) contains supplementary material, which is available to authorized users.

Bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors. A case series and analysis of cases reported in the Spanish pharmacovigilance database.

Bullous pemphigoid (BP) has been associated with dipeptidyl peptidase-4 inhibitors (DPP4i). Clinical features, outcomes, and risk of BP for new DPP4i (linagliptin, saxagliptin, and alopgliptin) are not well established. Comparison of risk of BP appearance for DPP4i and other oral antidiabetic drugs (OADs) such as sodium glucose cotransporter 2 inhibitors has not been studied to date. To describe the prevalence, sociodemographic, clinical, and histopathological characteristics, and outcome after drug withdrawal in DPP-4i-associated BP cases from our hospital. To review all Spanish spontaneous notifications of BP where DPP4i or OADs were included as suspected drugs and calculate the reporting odds ratios (RORs). A retrospective observational study was performed examining the association between DDP4i and BP. Clinical features and RORs were analyzed. Data from the Spanish Pharmacovigilance System (SEFV) are included. In our center, 28 of 89 patients with BP (31.5%) were under DPP4i treatment; 53.6% were male, and mean age was 80.8years. BP debuted the first year after DPP4i in 57.2%. BP control was achieved within 3.7months after drug withdrawal. Regarding SEFV, 22 of 972 spontaneous notifications were related to BP and DPP4i. RORs were superior for DPP4i compared to other OADs. Vildagliptin had the highest ROR. We present the largest DPP4i-induced BP case series in a single center, with a detailed study of the sociodemographic, clinical, and histopathological characteristics of each patient, and their treatment and outcome. Vildagliptin had the highest risk. DPP4i-associated BP does not seem to have specific clinical characteristics.

Characteristics of Patients with Diabetes Initiating Sodium Glucose Co-transporter-2 Inhibitors (SGLT2i): Real-World Results from Three Administrative Databases in Japan.

IntroductionThe aim of this study was to evaluate the characteristics of new users of sodium glucose co-transporter-2 inhibitors (SGLT2i) in comparison with those of new users of other oral antidiabetic drugs (OADs) using data retrieved from three administrative databases in Japan.MethodsThis study included adult patients from each database who started an OAD between 2014 and 2017. Outpatients who started SGLT2i therapy were included in the SGLT2i cohort. The remaining outpatients were grouped according to the OAD class of their earliest initial prescription after no use of the index OAD during the 6-month pre-index period. Diabetes-related complications were evaluated using the Diabetes Complication Severity Index.ResultsIn total, 176,355 patients in the hospital-based administrative database (H-dataset), 98,361 in the pharmacy claims database (P-dataset) and 37,786 in the insurance claims database (I-dataset) were analyzed. In the H-dataset, SGLT2i users, compared with users of other OADs, tended to be younger (mean age at index: 57.7 vs. 60.3–69.2 years) and to have a higher prevalence of hypercholesterolemia (73.5 vs. 55.2–71.4%), a higher mean body weight (74.4 vs. 60.5–70.8 kg), a higher body mass index (27.6 vs. 23.5–26.4 kg/m2) and a higher glycated hemoglobin level (8.4 vs. 7.4–8.1%). There were no distinct differences in the prevalence of complications between SGLT2i users and users of other OADs in the H-dataset. Similar trends were noted in the other datasets.ConclusionPatients initiating SGLT2i therapy differed in several characteristics from new users of other OADs. SGLT2i were prescribed more frequently to younger patients, those at increased cardiovascular risk or those with poorer glycemic control.FundingAstellas Pharma Inc., Tokyo, Japan.Electronic supplementary materialThe online version of this article (10.1007/s13300-019-0577-7) contains supplementary material, which is available to authorized users.

EADSG Guidelines: Insulin Therapy in Diabetes.

Executive Summary and Recommendations A diagnosis of diabetes or hyperglycemia should be confirmed prior to ordering, dispensing, or administering insulin (A).Insulin is the primary treatment in all patients with type 1 diabetes mellitus (T1DM) (A).Typically, patients with T1DM will require initiation with multiple daily injections at the time of diagnosis. This is usually short-acting insulin or rapid-acting insulin analogue given 0 to 15 min before meals together with one or more daily separate injections of intermediate or long-acting insulin. Two or three premixed insulin injections per day may be used (A).The target glycated hemoglobin A1c (HbA1c) for all children with T1DM, including preschool children, is recommended to be < 7.5% (< 58 mmol/mol). The target is chosen aiming at minimizing hyperglycemia, severe hypoglycemia, hypoglycemic unawareness, and reducing the likelihood of development of long-term complications (B).For patients prone to glycemic variability, glycemic control is best evaluated by a combination of results with self-monitoring of blood glucose (SMBG) (B).Indications for exogenous insulin therapy in patients with type 2 diabetes mellitus (T2DM) include acute illness or surgery, pregnancy, glucose toxicity, contraindications to or failure to achieve goals with oral antidiabetic medications, and a need for flexible therapy (B).In T2DM patients, with regards to achieving glycemic goals, insulin is considered alone or in combination with oral agents when HbA1c is ≥ 7.5% (≥ 58 mmol/mol); and is essential for treatment in those with HbA1c ≥ 10% (≥ 86 mmol/mol), when diet, physical activity, and other antihyperglycemic agents have been optimally used (B).The preferred method of insulin initiation in T2DM is to begin by adding a long-acting (basal) insulin or once-daily premixed/co-formulation insulin or twice-daily premixed insulin, alone or in combination with glucagon-like peptide-1 receptor agonist (GLP-1 RA) or in combination with other oral antidiabetic drugs (OADs) (B).If the desired glucose targets are not met, rapid-acting or short-acting (bolus or prandial) insulin can be added at mealtime to control the expected postprandial raise in glucose. An insulin regimen should be adopted and individualized but should, to the extent possible, closely resemble a natural physiologic state and avoid, to the extent possible, wide fluctuating glucose levels (C).Blood glucose monitoring is an integral part of effective insulin therapy and should not be omitted in the patient’s care plan. Fasting plasma glucose (FPG) values should be used to titrate basal insulin, whereas both FPG and postprandial glucose (PPG) values should be used to titrate mealtime insulin (B).Metformin combined with insulin is associated with decreased weight gain, lower insulin dose, and less hypoglycemia when compared with insulin alone (C).Oral medications should not be abruptly discontinued when starting insulin therapy because of the risk of rebound hyperglycemia (D).Analogue insulin is as effective as human insulin but is associated with less postprandial hyperglycemia and delayed hypoglycemia (B).The shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular (IM) injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them (A).Many patients in East Africa reuse syringes for various reasons, including financial. This is not recommended by the manufacturer and there is an association between needle reuse and lipohypertrophy. However, patients who reuse needles should not be subjected to alarming claims of excessive morbidity from this practice (A).Health care authorities and planners should be alerted to the risks associated with syringe or pen needles 6 mm or longer in children (A).

Effectiveness and Tolerability of Second-Line Therapy with Vildagliptin Versus Other Oral Agents in Type 2 Diabetes (EDGE): Post Hoc Sub-Analysis of Bulgarian Data.

Objectives Metformin is an established first-line treatment for type 2 diabetes mellitus (T2DM) patients but intensification of oral anti-diabetic therapy is usually required over time. The effectiveness of diabetes control with vildaGliptin and vildagliptin/mEtformin (EDGE) study compared effectiveness and safety of vildagliptin and other oral anti-diabetic drugs (OAD) in 45,868 patients worldwide with inadequately controlled T2DM by monotherapy under real-life conditions. Here, we present effectiveness results for patients receiving vildagliptin (vildagliptin cohort) or another OAD (comparator cohort) add-on to monotherapy in Bulgaria.MethodsThe eligible diabetes patients inadequately controlled with current monotherapy were assigned to add-on treatment, which was chosen by the physician based on patient’s need. Effectiveness was assessed by glycated hemoglobin (HbA1c) drop and by means of a composite endpoint assessing the proportion of patients responding to treatment (HbA1c <7%) without proven hypoglycemic event and significant weight gain (>5%) after 12 months of treatment.ResultsIn total, 754 patients were enrolled in Bulgaria, 384 in the vildagliptin cohort and 369 in the comparator cohort. Mean HbA1c change from baseline was significantly higher with vildagliptin compared to the comparator (−1.35% in the vildagliptin cohort and −0.55% in the comparator cohort, P < 0.001). In the vildagliptin cohort, a higher proportion of patients reached the composite endpoint (HbA1c <7%, no hypoglycemic events, no weight gain) when compared to the comparator cohort (vildagliptin: 32.3%; comparator: 8.4%; P < 0.001). Overall, vildagliptin was well tolerated with similarly low incidences of total adverse events (3.4% versus 1.9% in the comparator group) and serious adverse events (2.3% versus 1.1% in the comparator group).ConclusionsIn real-life clinical practice in Bulgaria, vildagliptin is associated with a greater HbA1c drop, and a higher proportion of patients reaching target HbA1c without hypoglycemia and weight gain compared to comparator.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-014-0083-x) contains supplementary material, which is available to authorized users.

Insulin Therapy in Type 2 Diabetes

Due to the progressive nature of Type 2 diabetes, insulin therapy is often required to achieve glycemic control. When lifestyle modifications and treatment with metformin with or without other oral antidiabetic drugs (OADs) have failed to achieve normoglycemia, timely initiation of singledose basal insulin treatment is a convenient, effective, and recommended strategy. The development of the long-acting basal insulin analogs, insulin detemir (IDet) and insulin glargine (IGlar), has resulted in significant improvements in the management of Type 2 diabetes, and specifically, in reducing rates of hypoglycemia. However, hypoglycemia still remains a limiting factor in the intensification of insulin therapy. Combination regimens involving insulin and incretin-based therapies have resulted in improved glycemic control with a similar rate of hypoglycemia compared with insulin alone. Novel basal insulin analogs may also help address the unmet needs associated with basal insulin therapy. Insulin degludec (IDeg) is a basal insulin analog that offers an ultra-long duration of action of more than 42 hours in adults, more flexibility compared with other long-acting insulin analogs in terms of daily dosing times, and reduced rates of hypoglycemia. Pegylated (PEG) lispro, an agent that is currently in clinical development, also offers an extended duration of action. The potential for fewer hypoglycemic episodes offered by combined regimens and new agents may improve adherence to insulin regimens.

Fifty-two-week, randomized, multicenter trial to compare the safety and efficacy of the novel glucagon-like peptide-1 analog liraglutide vs glibenclamide in patients with type 2 diabetes.

Aims/Introduction: We compared the safety and efficacy of liraglutide vs glibenclamide in patients with poorly controlled (HbA1c, 7.4-10.4%) type 2 diabetes. Subjects were randomly assigned at a 1:2 ratio to receive 1-year treatment with glibenclamide 1.25-2.5 mg/day or liraglutide 0.9 mg/day. Other oral anti-diabetic drugs (OAD) were prohibited during the trial. Adverse events (AE) were monitored. A total of 400 patients (liraglutide group, n = 268; glibenclamide group, n = 132) were randomized and exposed to trial products. At week 52 vs baseline, HbA1c in the liraglutide and glibenclamide groups was reduced from 9.3 to 7.8% and from 9.2 to 8.2%, respectively. Treatment difference (liraglutide - glibenclamide) at the end of the study was -0.49 (95% CI, -0.71 to -0.27). In the liraglutide and glibenclamide groups, Japan Diabetes Society target HbA1c < 6.9% was achieved by 22.1 and 8.5% of patients, respectively. Fasting plasma glucose fell from 202.8 and 202.1 mg/dL, respectively, to 145.3 and 156.7 mg/dL, respectively. Mean plasma glucose and mean postprandial plasma glucose increment were lower in the liraglutide group. Mean bodyweight was reduced by -0.8 kg in the liraglutide group and increased by 1.0 kg in the glibenclamide group. The proportion of patients reporting at least one treatment-emergent AE (TEAE) in the liraglutide and glibenclamide groups was 91.4 and 91.7%, respectively. Most TEAE were mild in severity. No major hypoglycemic episode was observed. Once-daily administration of liraglutide 0.9 mg for 52 weeks provides more favorable metabolic control and safety profile compared with glibenclamide. Patients on liraglutide lost bodyweight, whereas those on glibenclamide gained weight. This trial was registered with ClinicalTrial.gov (no. NCT00393718). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00128.x, 2011).

Effects of Pioglitazone and Metformin Fixed‐Dose Combination Therapy on Cardiovascular Risk Markers of Inflammation and Lipid Profile Compared With Pioglitazone and Metformin Monotherapy in Patients With Type 2 Diabetes

. Type 2 diabetes mellitus (T2DM) treatment should not increase cardiovascular (CV) risk and at best could provide benefit beyond lowering glucose. Pioglitazone has demonstrated a favorable CV profile relative to other oral antidiabetic drugs (OADs) in outcome and observational studies. This randomized, double-blind, parallel-group controlled study examined circulating biomarkers of CV risk in T2DM patients receiving a fixed-dose combination (FDC) of pioglitazone/metformin compared with the respective monotherapies. Patients with stable glycosylated hemoglobin (HbA(1c) ) for 3 months taking no OADs were treated with pioglitazone 15mg/metformin 850mg FDC twice daily (bid), pioglitazone 15mg bid, or metformin 850mg bid for 24 weeks. FDC and pioglitazone increased high-density lipoprotein cholesterol by 14.20% and 9.88%, respectively, vs an increase of 6.09% with metformin (P<.05, metformin vs FDC). Triglycerides decreased with all three treatments -5.95%, -5.54% and -1.78%, respectively; P=not significant). FDC and pioglitazone significantly decreased small low-density lipoprotein and increased large low-density lipoprotein particle concentrations. Reductions in high-sensitivity C-reactive protein were greater in the FDC and pioglitazone groups. Increases in adiponectin were significant in the FDC and pioglitazone groups (P<.0001 vs metformin). Overall, adverse events were not higher with the FDC. Thus, treatment with the FDC resulted in improved levels of CV biomarkers, which were better than or equal to monotherapy.

Reaching HbA1c Goals with Saxagliptin in Combination with Other Oral Antidiabetic Drugs

A large percentage of individuals with type 2 diabetes in the United States are not reaching their glycemic goals. In response to data from large outcomes trials and newer classes of therapeutic agents, various organizations and opinion-forming bodies recently updated their clinical practice recommendations for type 2 diabetes. The recommendations, as set by the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD), the American Association of Clinical Endocrinologists/American College of Endocrinology, and the Canadian Diabetes Association, are similar in their emphasis on lifestyle modification and the importance of treating fasting and postprandial glucose, both of which are significant contributors to achieving glycated hemoglobin (HbA1c) targets. However, the recommendations differ in focus, depth, and specific treatment approaches. With the exception of the ADA/EASD consensus, dipeptidyl peptidase-4 (DPP-4) inhibitors have been included as alternative first- or second-line therapy due, in part, to their glucose-dependent mechanism of action that complements the actions of other oral antidiabetic drugs (OADs). The DPP-4 inhibitor, saxagliptin, demonstrates significant glycemia-lowering effects as monotherapy and in combination therapy, is weight neutral and well tolerated, and has a low risk of hypoglycemia. The added efficacy of saxagliptin in combination with other OADs in improving glycemic parameters has resulted in a significant proportion of patients achieving an HbA1c < 7% versus monotherapy or active comparator. Combination therapy with saxagliptin can thus offer a potential advantage in achieving glycemic goals for the majority of patients with type 2 diabetes without additional tolerability concerns.