insulin-glargine and dapagliflozin

Efficacy and safety of dapagliflozin plus saxagliptin (DAPA + SAXA) were compared with insulin glargine (INS) in patients with type 2 diabetes (T2D) in a 52-week extension study.. This international Phase 3 study randomized adults with T2D on metformin with/without sulphonylurea. They received DAPA + SAXA or INS for 24 weeks (short-term) with a 28-week (long-term) extension. Week 52 exploratory endpoints included adjusted mean change from baseline in glycated haemoglobin A. Of the 1163 patients enrolled, 643 received treatment; 600 (DAPA + SAXA, 306; INS, 294) entered the long-term phase. At 52 weeks, HbA1c [adjusted least squares (LS) mean; 95% confidence interval (CI)] decreased more with DAPA + SAXA (-1.5% [-1.6%, -1.4%]) than with INS (-1.3% [-1.4%, -1.1%]); the LS mean difference (95% CI) was -0.25% (-0.4%, -0.1%; P = 0.009). Total body weight reduced with DAPA + SAXA [LS mean (95% CI): -1.8 kg (-2.4, -1.3)] and increased with INS [LS mean (95% CI): +2.8 kg (2.2, 3.3)]. More patients on DAPA + SAXA (17.6%) achieved HbA1c <7.0% without hypoglycaemia versus those on INS (9.1%). Rescue medication was required by 77 patients (23.8%) and 97 patients (30.4%) in the DAPA + SAXA and INS groups, respectively.. DAPA + SAXA treatment was non-inferior to INS in reducing HbA1c and body weight, and in achieving optimal glycaemic control without hypoglycaemia in patients with T2D 52 weeks after initiation.

Topics: Adamantane; Adult; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptides; Double-Blind Method; Drug Therapy, Combination; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Metformin; Treatment Outcome

To examine diabetes remission following a short-term intensive metabolic intervention combining lifestyle and glucose-lowering approaches.. We conducted an open-label, randomized controlled trial in 154 patients with type 2 diabetes up to 8 years in duration on 0 to 2 glucose-lowering medications. Participants were randomized to (a) a 12-week intensive intervention comprising lifestyle approaches and treatment with insulin glargine, metformin, and dapagliflozin or (b) standard diabetes care. At 12 weeks, diabetes medications were discontinued in participants with hemoglobin A1c (HbA1C) < 7.3% (56 mmol/mol). Participants were then followed for diabetes relapse until 64 weeks. The primary outcome was complete or partial diabetes remission (HbA1C < 6.5% [48 mmol/mol] off chronic diabetes drugs) at 24 weeks. Main secondary outcomes were complete or partial diabetes remission at 36, 48, and 64 weeks.. The primary outcome was achieved in 19 (24.7%) intervention group participants and 13 (16.9%) control group participants at 24 weeks (relative risk [RR] 1.5; 95% confidence interval [CI], 0.8-2.7). The relative risks of remission at 36, 48, and 64 weeks were 2.4 (95% CI, 1.2-5.0), 2.1 (95% CI, 1.0-4.4), and 1.8 (95% CI, 0.7-4.7), respectively. In an exploratory analysis, the intervention reduced the hazard of diabetes relapse with overt hyperglycemia by 43% (hazard ratio 0.57; 95% CI, 0.39-0.81).. Our primary outcome of diabetes remission at 24 weeks was not statistically significantly different. However, our overall results suggest that some patients with early type 2 diabetes are able to achieve sustained diabetes remission following a short-term intensive intervention. Further studies are needed to optimize the combined therapeutic approach used.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exercise; Female; Glucosides; Glycated Hemoglobin; Healthy Lifestyle; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Metformin; Middle Aged; Recurrence; Remission Induction; Secondary Prevention; Time Factors; Treatment Outcome

Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Glucosides; Humans; Insulin Glargine; Metformin

To explore the beneficial effects of dapagliflozin and/or insulin glargine on the pancreatic beta cell mass and hepatic steatosis in db/db mice.. Six-week-old db/db mice were assigned to one of four groups: untreated (Placebo), treated with dapagliflozin (Dapa), treated with insulin glargine (Gla), or treated with dapagliflozin and insulin glargine (Dapa+Gla). After 8 weeks of treatment, we determined glucose tolerance, beta cell mass, hepatic lipid content and gene expression.. Glucose tolerance was significantly ameliorated in the three treated groups to the same degree compared with the Placebo group. Immunohistochemical analysis revealed that the pancreatic beta cell mass was significantly maintained in the Dapa and Dapa+Gla groups, but not in the Gla group, compared with the Placebo group (Placebo 2.25 ± 1.44 mg, Dapa 5.01 ± 1.63 mg, Gla 3.79 ± 0.96 mg, Dapa+Gla 5.19 ± 1.78 mg). However, the triglyceride content of the liver was markedly elevated in the Gla group compared with that in the other three groups (Placebo 24.1 ± 11.5 mg, Dapa 30.6 ± 12.9 mg, Gla 128 ± 49.7 mg, Dapa+Gla 54.4 ± 14.1 mg per gram liver). The expression levels of genes related to fatty acid synthesis and lipid storage were significantly upregulated in the Gla group.. Our results showed that beta cell mass was sustained and hepatic steatosis was prevented, after 8 weeks of treatment with either dapagliflozin or dapagliflozin plus insulin glargine, but not with insulin glargine alone, in db/db mice.

Topics: Animals; Benzhydryl Compounds; Fatty Acids; Gene Expression; Glucose Intolerance; Glucosides; Hypoglycemic Agents; Insulin Glargine; Insulin-Secreting Cells; Lipid Metabolism; Liver; Male; Mice; Non-alcoholic Fatty Liver Disease; Sodium-Glucose Transporter 2 Inhibitors; Triglycerides

Topics: Animals; Benzhydryl Compounds; Glucose; Glucosides; Insulin Glargine; Mice; Non-alcoholic Fatty Liver Disease; Sodium; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors

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.

Topics: Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are new antidiabetic drugs that regulate blood glucose levels by increasing urinary glucose excretion. In May 2015, the U.S. Food and Drug Administration (FDA) issued a warning that SGLT2 inhibitors may lead to ketoacidosis. In this report, we describe a case of life-threatening euglycemic ketoacidosis associated with SGLT2 inhibition and evaluate possible mechanisms and triggers.

Topics: Benzhydryl Compounds; Blood Glucose; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Drug Therapy, Combination; Glucosides; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Metformin; Middle Aged; Risk Factors; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors

The aim was to compare changes in HbA1c and body weight after initiation of dapagliflozin or basal insulin supported oral therapy (BOT) in type 2 diabetes patients in primary care practices.. Patients from 983 primary care practices who started dapagliflozin or BOT between December 2012 and July 2015 (index date, ID) were retrospectively analyzed (Disease Analyzer; Germany). Changes in HbA1c (%) and body weight (kg) were evaluated 90-270 days after ID. Propensity score (PS) matching (1:1) was used to adjust for differences in baseline clinical characteristics (180-0 days before ID: age, sex, health insurance, diabetologist care, glucose lowering therapy, HbA1c, body mass index) and duration (days) between start of therapies and last HbA1c or weight documentation after ID.. After PS matching, 766 dapagliflozin (mean ± SD; age: 63 ± 10 years; HbA1c: 8.9 ± 1.2%) and 766 BOT (age: 63 ± 10 years; HbA1c: 8.7 ± 1.1%) patients were included. HbA1c decreased by mean (SD) of 1.0% (1.3) in dapagliflozin and by 1.0% (1.4) in BOT patients after 90-270 days (HbA1c reduction; dapagliflozin vs BOT: -0.01%; P = .79). In 440 dapagliflozin users with available data, body weight (97.4 ± 19.9 kg) decreased by 3.1 (5.8) kg after 90-270 days, whereas no significant weight change was observed in 440 matched BOT patients (97.5 ± 19.9 kg) (weight reduction; dapagliflozin vs BOT: -3.0 kg; P < .05).. Initiation of dapagliflozin therapy reduced HbA1c similar to basal insulin with the additional benefit of weight reduction in type 2 diabetes patients treated in general practices.

Topics: Aged; Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Male; Middle Aged; Primary Health Care; Retrospective Studies