incretins and dapagliflozin

Topics: Animals; Benzhydryl Compounds; Diabetes Mellitus; Drug Therapy, Combination; Glucagon; Glucosides; Humans; Hypoglycemic Agents; Incretins; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors

To evaluate the efficacy and treatment satisfaction of dapagliflozin and liraglutide in T2DM patients with glucose poorly controlled after triple therapy.. In addition to the original therapeutic regimen, dapagliflozin (n=83) and liraglutide (n=89) once a day were added, respectively. Height, body weight, waist circumference, and blood pressure were recorded. FBG, 2hPBG, HbA1c, fasting C-peptide, HOMA-IR, blood lipid, eGFR, BUA and DTSQ were detected before the treatment and after 24 weeks of treatment.. At the end of 24 weeks of treatment, a follow-up visit was completed for 79 patients in the dapagliflozin group and 77 patients in the liraglutide group. The body weight of the patients in the dapagliflozin group and the liraglutide group decreased significantly (P<0.05). The HbA1c level in the dapagliflozin group decreased from 8.96 ± 1.23% to 7.03 ±0.74% (P< 0.01), more than that in the liraglutide group, namely, from 8.99 ± 1.34% to 7.24 ±0.77% (P< 0.01). After 12 weeks of treatment, eGFR in the dapagliflozin group first decreased and then increased after 12 weeks of treatment. The percentages of patients achieving combined endpoints in the two groups were of no statistical significance (P=0.204). And there were mild adverse events in both groups.. The add-on treatment of dapagliflozin and liraglutide had promising clinical outcomes in patients with T2DM and poorly controlled glucose after triple therapy, which include the improvement in blood glucose, insulin resistance, SBP, and renal function. However, the overall treatment satisfaction was higher in the dapagliflozin group.

Topics: Aged; Benzhydryl Compounds; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucagon-Like Peptide-1 Receptor; Glucosides; Glycated Hemoglobin; Glycemic Control; Humans; Incretins; Liraglutide; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome

Heart failure with preserved ejection fraction (HFpEF) is a multifactorial disease that constitutes several distinct phenotypes, including a common cardiometabolic phenotype with obesity and type 2 diabetes mellitus. Treatment options for HFpEF are limited, and development of novel therapeutics is hindered by the paucity of suitable preclinical HFpEF models that recapitulate the complexity of human HFpEF. Metabolic drugs, like glucagon-like peptide receptor agonist (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2i), have emerged as promising drugs to restore metabolic perturbations and may have value in the treatment of the cardiometabolic HFpEF phenotype. We aimed to develop a multifactorial HFpEF mouse model that closely resembles the cardiometabolic HFpEF phenotype, and evaluated the GLP-1 RA liraglutide (Lira) and the SGLT2i dapagliflozin (Dapa).. Aged (18-22 months old) female C57BL/6J mice were fed a standardized chow (CTRL) or high-fat diet (HFD) for 12 weeks. After 8 weeks HFD, angiotensin II (ANGII), was administered for 4 weeks via osmotic mini pumps. HFD + ANGII resulted in a cardiometabolic HFpEF phenotype, including obesity, impaired glucose handling, and metabolic dysregulation with inflammation. The multiple hit resulted in typical clinical HFpEF features, including cardiac hypertrophy and fibrosis with preserved fractional shortening but with impaired myocardial deformation, atrial enlargement, lung congestion, and elevated blood pressures. Treatment with Lira attenuated the cardiometabolic dysregulation and improved cardiac function, with reduced cardiac hypertrophy, less myocardial fibrosis, and attenuation of atrial weight, natriuretic peptide levels, and lung congestion. Dapa treatment improved glucose handling, but had mild effects on the HFpEF phenotype.. We developed a mouse model that recapitulates the human HFpEF disease, providing a novel opportunity to study disease pathogenesis and the development of enhanced therapeutic approaches. We furthermore show that attenuation of cardiometabolic dysregulation may represent a novel therapeutic target for the treatment of HFpEF.

Topics: Angiotensin II; Animals; Benzhydryl Compounds; Blood Glucose; Diet, High-Fat; Disease Models, Animal; Female; Fibrosis; Gene Expression Regulation; Glucagon-Like Peptide-1 Receptor; Glucosides; Heart Failure, Diastolic; Hypertrophy, Left Ventricular; Incretins; Liraglutide; Mice, Inbred C57BL; Myocardium; Signal Transduction; Sodium-Glucose Transporter 2 Inhibitors; Ventricular Function, Left; Ventricular Remodeling

Topics: Adamantane; Albuminuria; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Dipeptides; Double-Blind Method; Glucosides; Humans; Incretins; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2

In randomized controlled trials (RCTs), sodium-glucose co-transporter-2 (SGLT2) inhibitors have been shown to confer glycaemic and extra-glycaemic benefits. The DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) study was a multicentre retrospective study designed to evaluate the baseline characteristics of patients receiving dapagliflozin vs those receiving selected comparators (dipeptidyl peptidase-4 inhibitors, gliclazide, or glucagon-like peptide-1 receptor agonists), and drug effectiveness in routine clinical practice. From a population of 281 217, the analysis included 17 285 patients initiating dapagliflozin or comparator glucose-lowering medications (GLMs), 6751 of whom had a follow-up examination. At baseline, participants starting dapagliflozin were younger, had a longer disease duration, higher glycated haemoglobin (HbA1c) concentration, and a more complex history of previous GLM use, but the clinical profile of patients receiving dapagliflozin changed during the study period. Dapagliflozin reduced HbA1c by 0.7%, body weight by 2.7 kg, and systolic blood pressure by 3.0 mm Hg. Effects of comparator GLMs were also within the expected range, based on RCTs. This real-world study shows an initial channelling of dapagliflozin to difficult-to-treat patients. Nonetheless, dapagliflozin provided significant benefits with regard to glucose control, body weight and blood pressure that were in line with findings from RCTs.

Topics: Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Gliclazide; Glucagon-Like Peptide-1 Receptor; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Incretins; Italy; Male; Middle Aged; Retrospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

The impact of new classes of glucose lowering medications on markers of non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes (T2D) have been inconsistent in their magnitude and independence. This large retrospective study investigates changes in alanine aminotransferase (ALT) levels among subjects initiated on newer classes of T2D medications in comparison to a reference control group.. We studied people with T2D from a large Canadian diabetes register, who had canagliflozin, dapagliflozin, liraglutide, sitagliptin or no further treatment added to their diabetes treatments. Stepwise multiple regression was used to determine the association of A1c and weight change on ALT. Propensity score weighting was used to balance baseline characteristics between treatment groups.. A total of 3667 subjects met study criteria. ALT levels (mean follow-up 4.8 months) were lower after treatment with sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin (-4.3U/L, P<0.01) and dapagliflozin (-3.5U/L, P<0.01), compared to incretin agents, liraglutide (-2.1U/L, P<0.01) and sitagliptin (-1.8U/L, P<0.01), each greater than the control group. Only the SGLT2 inhibitor treatment groups maintained a significant ALT reduction vs. control following multivariable adjustment and propensity score weighting. Greater ALT reductions were seen with higher baseline ALT for both the SGLT2 inhibitor treatment groups.. SGLT2 inhibitors canagliflozin and dapagliflozin resulted in a weight and A1c-independent reduction of ALT levels compared to incretin agents, with a dose-response observed at higher baseline ALT levels. Further studies investigating the differential effects of these drug classes on NAFLD, and insulin/glucagon levels as potential mechanism explaining these differences, should be performed.

Topics: Aged; Aged, 80 and over; Alanine Transaminase; Benzhydryl Compounds; Canada; Canagliflozin; Diabetes Mellitus, Type 2; Female; Glucosides; Humans; Hypoglycemic Agents; Incretins; Liraglutide; Male; Middle Aged; Registries; Retrospective Studies; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

To evaluate the effectiveness and safety of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, dapagliflozin, in patients with type 2 diabetes mellitus (T2DM) and background glucagon-like peptide-1 receptor agonist (GLP1-RA) therapy.. This is a 12-month, real-world observational study, which assessed the effectiveness and safety of dapagliflozin in patients with T2DM and background GLP1-RA therapy. The main outcome measures were changes in A1C and weight at 6 and 12 months from baseline. Secondary outcomes were differences in A1C and weight reduction between this cohort and another group of patients with T2DM treated with dapagliflozin but without background GLP1-RA therapy. In total, 109 patients with GLP1-RA and 104 patients without GLP1-RA were included. Baseline mean A1C and weight in the GLP1-RA and non-GLP1-RA groups were 7.4% vs. 7.3% and 96.2 kg vs. 95.1 kg, respectively. A significant reduction in A1C was seen with dapagliflozin in both cohorts at 6 and 12 months (GLP1-RA: -0.51% and -0.34%, non-GLP1-RA: -0.69% and -0.62%, respectively, p < 0.0001 in all analyses). Weight was significantly reduced in both groups at 6 and 12 months (GLP1-RA: -2.3 kg and -2.4 kg, non-GLP1-RA: -3.9 kg and -4.8 kg, respectively, p < 0.0001 in all analyses). A1C reduction and weight loss were significantly lower in patients with GLP1-RA than in patients without GLP1-RAs. Drug discontinuation rates were similar in both cohorts.. Dapagliflozin, when added in real life to patients with T2DM treated with GLP1-RAs, induced a further significant, albeit modest improvement in A1C and a further weight loss.

Topics: Aged; Benzhydryl Compounds; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucagon-Like Peptide-1 Receptor; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Incretins; Male; Middle Aged; Retrospective Studies; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Spain; Time Factors; Treatment Outcome; Weight Loss