sitagliptin-phosphate and empagliflozin

Oral semaglutide is a tablet formulation of a glucagon-like peptide-1 receptor agonist (GLP-1RA), recently approved in the USA and other countries. This paper reviews data from clinical trials (PIONEER 1, 2, 3, and 7) comparing oral semaglutide (once-daily doses of 3, 7, or 14 mg) with either once-daily placebo, empagliflozin 25 mg, or sitagliptin 100 mg. After 26 weeks in PIONEER 1, patients randomized to 3, 7, or 14 mg doses of oral semaglutide monotherapy had statistically significant reductions in glycated hemoglobin (HbA

Topics: Administration, Oral; Benzhydryl Compounds; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Glucagon-Like Peptides; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Primary Health Care; Sitagliptin Phosphate

Glucagon-like peptide-1 (GLP-1) receptor agonists are highly potent antihyperglycemic drugs that impose low risk of hypoglycemia and also result in body weight reduction. Currently, all approved members of the class require administration by injection. Areas covered: This manuscript reviews oral semaglutide-an experimental GLP-1 receptor agonist in phase-3 clinical development. Available pharmacological and clinical data of the drug are reviewed, and important end-points described. Expert opinion: Oral peptide delivery has become possible with the discovery of absorption enhancers. The clinical development program of once-daily oral semaglutide has shown superiority in reducing glycosylated hemoglobin and body weight in comparison with placebo and active comparators (sitagliptin, liraglutide, and empagliflozin). Safety and tolerability of oral semaglutide is in line with injectable members of the class. Delayed gastric emptying, local increase in pH, and enhanced absorption do not seem to affect the exposure of a number of other oral drugs that have been tested (metformin, digoxin, oral contraceptive ethinylestradiol/levonorgestrel, lisinopril, warfarin, furosemide and rosuvastatin). Clinical questions for further investigation include the effectiveness and safety of oral semaglutide in cardiovascular indications.

Topics: Benzhydryl Compounds; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Glucosides; Humans; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Sitagliptin Phosphate

This article reviews evidence supporting sodium glucose cotransporter 2 (SGLT2) inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor combination therapy for management of type 2 diabetes mellitus (T2DM).. We conducted a nonsystematic review of the literature focusing on single-pill or fixed-dose combinations of SGLT2 inhibitors and DPP-4 inhibitors available in the United States.. SGLT2 inhibitors and DPP-4 inhibitors have complementary mechanisms of action that address several of the underlying pathophysiologic abnormalities present in T2DM without overlapping toxicities. The combination of these 2 agents has several advantages including a low risk of hypoglycemia, the potential for weight loss, the ability to coformulate into a pill with once-daily administration, and the possibility to use with other classes of glucose-lowering agents. Cardiovascular outcomes trials reported to date support the safety of the DPP-4 class and suggest possible cardioprotective effects for SGLT2 inhibitors - at least based on the first reported study that used empagliflozin. Recent clinical evidence shows that SGLT2 inhibitor/DPP-4 inhibitor therapy is an effective combination for T2DM treatment, providing glycated hemoglobin (HbA1c) reductions of 1.1 to 1.5%, and weight reductions of approximately 2 kg when added to metformin, which is its primary place in therapy.. The combination of an SGLT2 inhibitor/DPP-4 inhibitor is a safe and effective treatment choice for patients with T2DM who are unable to obtain adequate glycemic control with metformin therapy, cannot use metformin, or have a higher baseline HbA1c.. BP = blood pressure; CI = confidence interval; CVOT = cardiovascular outcomes; DKA = diabetic ketoacidosis; DPP-4 = dipeptidyl peptidase-4; EXAMINE = EXamination of cArdiovascular outcoMes with alogliptiN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome; FDA = Food and Drug Administration; HbA1c = glycated hemoglobin; HR = hazard ratio; MACE = major adverse cardiovascular events; SAVOR-TIMI 53 = Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Type 2 Diabetes Mellitus; SBP = systolic blood pressure; SGLT2 = sodium glucose cotransporter 2; TECOS = Trial to Evaluate Cardiovascular Outcomes after Treatment with Sitagliptin; T2DM = type 2 diabetes mellitus; XR = extended release.

Topics: Adamantane; Benzhydryl Compounds; Blood Glucose; Canagliflozin; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glucosides; Humans; Hypoglycemia; Hypoglycemic Agents; Linagliptin; Metformin; Piperidines; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome; Uracil

Type 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2I, also known as gliflozin) and a dipeptidyl peptidase-4 inhibitor (DPP-4I, also known as gliptin) appears to be an attractive strategy because of complementary modes of action. This narrative review analyzes the pharmacokinetics and clinical efficacy of different combined therapies with an SGLT2I (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, tofogliflozin) and DPP-4I (linagliptin, saxagliptin, sitagliptin, teneligliptin). Drug-drug pharmacokinetic interaction studies do not show any significant changes in peak concentrations (C

Topics: Adamantane; Benzhydryl Compounds; Canagliflozin; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glucosides; Humans; Linagliptin; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

Diabetes treatments aim at preventing undesirable metabolic effects of hyperglycemia and at preventing/reducing tissue damage, including cardiovascular (CV) events. For approval, novel diabetes drugs undergo early systematic investigation to assess CV safety. This review provides an updated analysis of the results of recent studies examining novel diabetes medications and CV outcomes.. The new regulatory guidelines enforce adjudication of all CV events when testing novel diabetes drugs. Endpoints of CV mortality, myocardial infarction (MI), stroke and hospitalization for heart failure (HF) were included in the most recent clinical studies on novel antihyperglycemics. These are: the incretin mimetics glucagon-like peptide 1 (GLP-1) receptor agonists (GLP1-RA), the incretin enhancers dipeptidylpeptidase-4 (DPP-4) inhibitors (DPP4-I or gliptins), and the sodium-glucose cotransporter (SGLT2) inhibitors (SGLT2-I or gliflozins). The studies ELIXA and EXAMINE, testing lixisenatide and alogliptin, respectively, revealed non-inferiority versus placebo in terms of CV safety. The SAVOR-TIMI 53 results confirmed overall CV safety of saxagliptin, but raised a warning related to the increase in the risk of hospitalization for HF in the saxagliptin group. Recently, TECOS revealed a particularly favorable CV profile for sitagliptin while EMPA-REG showed a significant CV risk reduction in empagliflozin treated subjects. Ongoing studies will provide additional data on CV safety for other GLP1-RAs, DPP4-I and SGLT2-I.. Results of safety outcome studies focused on CV events, including HF and mortality for CV causes, are not homogeneous. A critical analysis of these studies may help cardiologists and diabetes specialists to adapt their therapeutic choices to individual patients.

Topics: Benzhydryl Compounds; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucosides; Humans; Hypoglycemic Agents; Incretins; Patient Safety; Patient Selection; Risk Assessment; Risk Factors; Sitagliptin Phosphate; Treatment Outcome

This Practice Pearl provides a review and brief commentary of the 24-week, double-blind, parallel-group, randomized, Phase III study by Roden et al., which assessed the efficacy and safety of the sodium-glucose cotransporter 2 inhibitor empagliflozin, 10 mg or 25 mg as monotherapy, versus placebo and the dipeptidyl peptidase-4 inhibitor sitagliptin, in previously untreated patients with type 2 diabetes mellitus (T2DM). Compared to placebo, empagliflozin improved glycemic control, with additional benefits on bodyweight and systolic blood pressure, versus placebo and sitagliptin. Treatment was well tolerated. The authors concluded that empagliflozin is a potential new approach to treat patients with T2DM who are inadequately controlled with diet and exercise alone. This paper advances our understanding of empagliflozin, which so far, appears to be a promising therapeutic option for the management of patients with T2DM.

Topics: Adult; Benzhydryl Compounds; Blood Pressure; Diabetes Mellitus, Type 2; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Weight Loss

To compare the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 inhibitors on ectopic fat accumulation and tissue-specific insulin sensitivity.. This randomized controlled trial enrolled 44 patients with type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). They were randomly assigned to receive either empagliflozin 10 mg/day or sitagliptin 100 mg/day for 12 weeks. The primary endpoint was the change in intrahepatic lipid content (IHL) measured using proton magnetic resonance spectroscopy (. At baseline, the mean duration of diabetes, HbA1c level and IHL were 3.7 years, 7.2% and 20.9%, respectively. The median NAFLD activity score was 3.0. IHL was significantly more decreased in the empagliflozin group than that in the sitagliptin group (between-group difference was -5.2% ± 1.1% and -1.9% ± 1.2%, respectively, (95% confidence interval); -3.3 (-6.5, -0.1), P = .044). However, there were no significant between-group differences in the change of insulin sensitivity in the liver, muscle or adipose tissues. Interestingly, hepatic insulin sensitivity was significantly increased only in the empagliflozin group and was significantly negatively associated with the change in IHL.. Empagliflozin significantly improves hepatic steatosis compared with sitagliptin, and this may protect against subsequent hepatic insulin resistance. Early administration of SGLT2 inhibitors is preferable for T2D patients with NAFLD.

Topics: Diabetes Mellitus, Type 2; Glucose; Humans; Insulin Resistance; Lipids; Non-alcoholic Fatty Liver Disease; Prospective Studies; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors

This study aimed to compare 12.5 mg empagliflozin effectiveness and safety vs. 50 mg sitagliptin twice daily as an add-on triple medication in Egyptians with type 2 diabetes.. Patients with hemoglobin A1c (HbA1c) between 53 and 86 mmol/mol after receiving open-label either sitagliptin 50 mg (n = 85) or empagliflozin 12.5 mg (n = 85) twice daily for 12 weeks were afterward taken into account for the administration of open-label empagliflozin 12.5 mg (n = 40) and sitagliptin 50 mg (n = 28) respectively twice daily for another 12 weeks of treatment as an added-on triple therapy. Both groups of patients kept taking metformin and empagliflozin 12.5 mg or sitagliptin 50 mg twice daily as prescribed. The HbA1c change from baseline after 12 weeks of triple-added-on therapy was the main endpoint.. The sitagliptin group receiving empagliflozin saw a substantial drop in HbA1c, fasting and postprandial plasma glucose levels, body weight, and blood pressure compared to the starting point. As opposed to that, adding sitagliptin to the empagliflozin group non-significantly reduced HbA1c, fasting, and postprandial plasma glucose levels, and systolic blood pressure from baseline but significantly reduced body weight and diastolic blood pressure. Comparing the two groups, adding empagliflozin significantly reduced HbA1c, fasting, and postprandial plasma glucose levels (p < 0.001 for all except fasting plasma glucose level, p = 0.002). While the patient's weight and blood pressure were not significantly affected.. Empagliflozin was superior to sitagliptin in relation to glycemic control, weight, and systolic/diastolic blood pressure reduction.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Egypt; Glycated Hemoglobin; Humans; Metformin; Sitagliptin Phosphate

The mechanism through which sodium-glucose cotransporter 2 inhibitors (SGLT2i) prevent the incidence of heart failure and/or affect cardiac structure and function remains unclear.. The EMPA-HEART trial is aimed at verifying whether empagliflozin improves myocardial contractility (left ventricle global longitudinal strain, LV-GLS) and/or cardiopulmonary fitness (peak oxygen uptake, VO2peak) in subjects with type 2 diabetes (T2D) without heart disease. Patients with T2D, normal LV systolic function (2D-Echo EF > 50%), and no heart disease were randomized to either empagliflozin 10 mg or sitagliptin 100 mg for 6 months and underwent repeated cardiopulmonary exercise tests with echocardiography and determination of plasma biomarkers.. Empagliflozin has neutral impact on both LV-GLS and exercise tolerance in subjects with T2D and normal left ventricular function. However, in patients with subclinical dysfunction (LV-GLS < 16.5%) it produces a rapid and sustained amelioration of LV contractility. Trial registration EUDRACT Code 2016-002225-10.

Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Glucosides; Heart Ventricles; Humans; Oxygen; Sitagliptin Phosphate

While the cardioprotective benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors have been established in patients with cardiovascular disease (CVD), their advantages over other anti-diabetic drugs at earlier stages remain unclear. We compared the cardioprotective effects of empagliflozin, an SGLT2 inhibitor, with those of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, focusing on cardiac fat accumulation, cardiac function, and cardiac metabolism in patients with early-stage type 2 diabetes mellitus (T2DM) without CVD complications.. This was a prospective, randomized, open-label, blinded-endpoint, parallel-group trial that enrolled 44 Japanese patients with T2DM. The patients were randomized for 12-week administration of empagliflozin or sitagliptin. Pericardial fat accumulation and myocardial triglyceride content were evaluated by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Echocardiography,. The patients were middle-aged (50.3 ± 10.7 years, mean ± standard deviation) and overweight (body mass index 29.3 ± 4.9 kg/m. Although the effects on cardiac fat and function were not statistically different between the two groups, empagliflozin exhibited superior effects on cardiometabolic biomarkers, such as uric acid, high-density lipoprotein cholesterol, ketone bodies, and insulin sensitivity. Therefore, when considering the primary preventive strategies for CVD, early supplementation with SGLT2 inhibitors may be more beneficial than DPP-4 inhibitors, even in patients with early-stage T2DM without current CVD complications.. UMIN000026340; registered on February 28, 2017. https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000030257.

Topics: Adiposity; Adult; Benzhydryl Compounds; Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Energy Metabolism; Female; Glucosides; Glycated Hemoglobin; Heart; Humans; Male; Middle Aged; Myocardium; Primary Prevention; Prospective Studies; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Tokyo; Treatment Outcome

To investigate the long-term efficacy and safety of empagliflozin monotherapy compared with placebo and sitagliptin in drug-naïve patients with type 2 diabetes mellitus.. Of 899 patients randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, placebo, or sitagliptin 100 mg once daily for 24 weeks, 615 continued in a double-blind extension trial for ≥52 weeks. Exploratory endpoints included changes from baseline in HbA1c, weight and blood pressure at week 76.. Compared with placebo, adjusted mean changes from baseline in HbA1c at week 76 were -0.78 % (95 % CI -0.94, -0.63; p < 0.001) and -0.89 % (95 % CI -1.04, -0.73; p < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Compared with placebo, adjusted mean changes from baseline in weight at week 76 were -1.8 kg (95 % CI -2.4, -1.3; p < 0.001) and -2.0 kg (95 % CI -2.6, -1.5; p < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Empagliflozin led to reductions in systolic blood pressure (SBP) compared with placebo in the primary analysis but not in sensitivity analyses. Compared with sitagliptin, empagliflozin 25 mg reduced HbA1c and both empagliflozin doses reduced weight and SBP. Adverse events (AEs) were reported in 76.8, 78.0, 76.4 and 72.2 % of patients on empagliflozin 10 mg, empagliflozin 25 mg, placebo and sitagliptin, respectively. Confirmed hypoglycaemic AEs (glucose ≤3.9 mmol/l and/or requiring assistance) were reported in two patients (0.9 %) per treatment group.. Empagliflozin monotherapy for ≥76 weeks was well tolerated and led to sustained reductions in HbA1c and weight compared with placebo.. clinicaltrials.gov NCT01289990.

Topics: Adult; Aged; Benzhydryl Compounds; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Sitagliptin Phosphate; Time Factors; Treatment Outcome; Weight Loss

To investigate the long-term safety and efficacy of empagliflozin, a sodium glucose cotransporter 2 inhibitor; sitagliptin; and metformin in patients with type 2 diabetes.. In this randomized, open-label, 78-week extension study of two 12-week, blinded, dose-finding studies of empagliflozin (monotherapy and add-on to metformin) with open-label comparators, 272 patients received 10 mg empagliflozin (166 as add-on to metformin), 275 received 25 mg empagliflozin (166 as add-on to metformin), 56 patients received metformin, and 56 patients received sitagliptin as add-on to metformin.. Changes from baseline in HbA1c at week 90 were -0.34 to -0.63% (-3.7 to -6.9 mmol/mol) with empagliflozin, -0.56% (-6.1 mmol/mol) with metformin, and -0.40% (-4.4 mmol/mol) with sitagliptin. Changes from baseline in weight at week 90 were -2.2 to -4.0 kg with empagliflozin, -1.3 kg with metformin, and -0.4 kg with sitagliptin. Adverse events (AEs) were reported in 63.2-74.1% of patients on empagliflozin and 69.6% on metformin or sitagliptin; most AEs were mild or moderate in intensity. Hypoglycemic events were rare in all treatment groups, and none required assistance. AEs consistent with genital infections were reported in 3.0-5.5% of patients on empagliflozin, 1.8% on metformin, and none on sitagliptin. AEs consistent with urinary tract infections were reported in 3.8-12.7% of patients on empagliflozin, 3.6% on metformin, and 12.5% on sitagliptin.. Long-term empagliflozin treatment provided sustained glycemic and weight control and was well tolerated with a low risk of hypoglycemia in patients with type 2 diabetes.

Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Glucagon-Like Peptide 1; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Pyrazines; Sitagliptin Phosphate; Time Factors; Treatment Outcome; Triazoles

We aimed to investigate the efficacy and tolerability of empagliflozin, an oral, potent, and selective inhibitor of sodium-glucose co-transporter 2, in patients with type 2 diabetes who had not received drug treatment in the preceding 12 weeks.. In our multicentre, randomised, placebo-controlled, phase 3 trial, we enrolled adults (aged ≥18 years) who had not received oral or injected anti-diabetes treatment in the previous 12 weeks. Eligible patients had HbA1c concentrations of 7-10%. We randomly allocated patients (1:1:1:1) with a computer-generated random sequence, stratified by region, HbA1c, and estimated glomerular filtration rate at screening, to placebo, empagliflozin 10 mg, empagliflozin 25 mg, or sitagliptin 100 mg once daily for 24 weeks. Patients and investigators were masked to treatment assignment. The primary endpoint was change from baseline in HbA1c at week 24 by ANCOVA in all randomly allocated patients who were treated with at least one dose of study drug and had a baseline HbA1c value. This study is completed and registered with ClinicalTrials.gov, number NCT01177813.. Between Aug 12, 2010, and March 19, 2012, we randomly allocated 228 patients to receive placebo, 224 to receive empagliflozin 10 mg, 224 to receive empagliflozin 25 mg, and 223 to receive sitagliptin. Compared with placebo, adjusted mean differences in change from baseline HbA1c at week 24 were -0·74% (95% CI -0·88 to -0·59; p<0·0001) for empagliflozin 10 mg, -0·85% (-0·99 to -0·71; p<0·0001) for empagliflozin 25 mg, and -0·73% (-0·88 to -0·59; p<0·0001) for sitagliptin. 140 (61%) patients in the placebo group reported adverse events (four [2%] severe and six [3%] serious), as did 123 (55%) patients in the empagliflozin 10 mg group (eight [4%] severe and eight [4%] serious), 135 (60%) patients in the empagliflozin 25 mg group (seven [3%] severe and five [2%] serious), and 119 (53%) patients in the sitagliptin group (five [2%] severe and six [3%] serious).. Empagliflozin provides a tolerable and efficacious strategy to reduce HbA1c in patients with type 2 diabetes who had not previously received drug treatment.. Boehringer Ingelheim and Eli Lilly.

Topics: Analysis of Variance; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glomerular Filtration Rate; Glucosides; Glycated Hemoglobin; Humans; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Triazoles

This randomized, open-label, crossover study investigated potential drug-drug interactions between the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin and the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin. Empagliflozin is a potent and selective SGLT-2 inhibitor that lowers blood glucose levels by inhibiting renal glucose reabsorption, leading to an increase in urinary glucose excretion. Sitagliptin lowers blood glucose through an insulin-dependent mechanism of action.. Sixteen healthy male volunteers received three treatments (A, B, C) in one of two treatment sequences (AB then C, or C then AB). In treatment AB, 50 mg empagliflozin was administered once daily (q.d.) for 5 days (treatment A), immediately followed by coadministration of 50 mg empagliflozin q.d. and 100 mg sitagliptin q.d. over 5 days (treatment B). In treatment C, 100 mg sitagliptin was administered q.d. for 5 days. A washout period of ≥7 days separated treatments AB and C.. Coadministration of sitagliptin with empagliflozin did not have a clinically relevant effect on the area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ (AUC(τ,ss)) (geometric mean ratio [GMR] 110.4; 90% confidence interval [CI] 103.9, 117.3) or maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (C (max,ss)) (GMR 107.6; 90% CI 97.0, 119.4) of empagliflozin. Coadministration of empagliflozin with sitagliptin did not have a clinically meaningful effect on the AUC(τ,ss) (GMR 103.1; 90% CI 98.9, 107.3) or C (max,ss) (GMR 108.5; 90% CI 100.7, 116.9) of sitagliptin. Empagliflozin and sitagliptin were well tolerated when given alone or in combination. Five subjects (31.3%) reported at least one adverse event (AE): three (18.8%) experienced an AE while receiving empagliflozin monotherapy and three (18.8%) while receiving sitagliptin monotherapy. No adverse events were reported during the coadministration period. No AEs were regarded as drug-related by the investigator.. These results indicate that empagliflozin and sitagliptin can be coadministered without dose adjustments.

Topics: Area Under Curve; Benzhydryl Compounds; Cross-Over Studies; Dipeptidyl-Peptidase IV Inhibitors; Drug Interactions; Glucosides; Humans; Hypoglycemic Agents; Male; Pyrazines; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Triazoles

We aimed to evaluate patient preferences towards three oral antihyperglycaemic therapies using conjoint analysis to determine which attributes may influence use.. We used an online survey, completed by 553 US respondents with type 2 diabetes mellitus (T2DM; mean age 64 ± 9 years; 55% had cardiovascular [CV] risk; 27% had CV disease), to present hypothetical, blinded, pairwise, drug profile comparison choices, between different benefit/risk attributes and effect ranges. Attributes were derived from phase 3 trials for empagliflozin 25 mg (SGLT2 inhibitor), oral semaglutide 14 mg (GLP-1 receptor agonist) and sitagliptin 100 mg (DPP-4 inhibitor). Predicted therapy preference outcomes and relative importance of each attribute were calculated (presented as a percentage).. Preference score was highest for the profile matching empagliflozin (56%), versus sitagliptin (38%; z-test, P < 0.001) and oral semaglutide (6%, z-test, P < 0.001). Results were overall consistent in subgroup analyses. Genital infection risk was the most important attribute (relative score: 19% [z-test, P = 0.077]). Other important attributes were fasting requirements (15%), weight reduction (15%), risk of vomiting (14%), CV benefit (12%), and risk of nausea (11%). HbA1c reduction (8%) and ability to take medication with other drugs (6%) were considered less important. While blinded to drug name/dose, respondents chose a drug profile similar to empagliflozin (41%) versus sitagliptin (31%), oral semaglutide (11%), or 'none of the options' (17%).. While the drug profile comparable to empagliflozin was preferred, CV benefit was not the top patient priority. A shared physician-patient decision model and increased patient education are needed to ensure optimal use of guideline-directed T2DM therapies.

Topics: Adult; Aged; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Middle Aged; Patient Preference; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors

The effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with heart failure (HF) in routine clinical practice is not extensively studied. This study aimed to evaluate the comparative effectiveness of SGLT2i vs. sitagliptin in older adults with HF and type 2 diabetes and to investigate whether there were any differences between agents within the SGLT2i class or for reduced and preserved ejection fraction.. Using Medicare claims data (April 2013 to December 2019), 16 253 SGLT2i initiators vs. 43 352 initiators of sitagliptin aged ≥65 years with type 2 diabetes and HF were included. The primary outcome was a composite of all-cause mortality, hospitalization for HF or urgent visit requiring intravenous diuretics; secondary outcomes included its individual components. Propensity score fine stratification weighted Cox regression was used to adjust for 100 pre-exposure characteristics. Mean age was 74 years; 49.8% were women. Initiation of SGLT2i vs. sitagliptin was associated with a lower risk of the primary composite outcome [adjusted hazard ratio (HR) 0.72; 95% confidence interval 0.67-0.77]. The adjusted HRs were 0.70 (0.63-0.78) for all-cause mortality, 0.64 (0.58-0.70) for hospitalization for HF, and 0.77 (0.69-0.86) for urgent visit requiring intravenous diuretics. Similar associations with the primary composite outcome were observed for all three agents within the SGLT2i class, for reduced and preserved ejection fraction, and subgroups based on demographics, comorbidities, and other HF treatments. Bias-calibrated HRs for the primary endpoint using negative and positive control outcomes ranged between 0.81 and 0.89, suggesting that the observed benefit could not be fully explained by residual confounding.. In routine US clinical practice, SGLT2i demonstrated robust clinical effectiveness in older adults with HF and type 2 diabetes compared with sitagliptin, with no evidence of heterogeneity across the SGLT2i class or across ejection fraction.

Topics: Aged; Benzhydryl Compounds; Canagliflozin; Cohort Studies; Diabetes Mellitus, Type 2; Female; Glucosides; Heart Failure; Heart Failure, Diastolic; Hospitalization; Humans; Male; Medicare; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Metformin; Sitagliptin Phosphate; Treatment Outcome

Novel glucagon-like peptide-1 (GLP-1) receptor agonist oral semaglutide has demonstrated greater improvements in glycated hemoglobin (HbA1c) and body weight versus oral medications empagliflozin and sitagliptin, and injectable GLP-1 analog liraglutide, in the PIONEER clinical trial program. Based on these data, the present analysis aimed to evaluate the long-term cost-effectiveness of oral semaglutide versus empagliflozin, sitagliptin and liraglutide in Spain.. Outcomes were projected over patients' lifetimes using the IQVIA CORE Diabetes Model (v9.0), discounted at 3.0% annually. Cohort characteristics and treatment effects were sourced from PIONEER 2 and 4 for the comparisons of oral semaglutide 14 mg versus empagliflozin 25 mg and liraglutide 1.8 mg, respectively, and PIONEER 3 for oral semaglutide 7 and 14 mg versus sitagliptin 100 mg. Costs were accounted from a healthcare payer perspective in 2020 euros (EUR). Patients were assumed to receive initial therapies until HbA1c exceeded 7.5% and then treatment-intensified to basal insulin.. Oral semaglutide 14 mg was associated with improvements in quality-adjusted life expectancy of 0.13, 0.19 and 0.06 quality-adjusted life years (QALYs) versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg, respectively, with direct costs EUR 168 higher versus empagliflozin and EUR 236 and 1415 lower versus sitagliptin and liraglutide, respectively. Oral semaglutide 14 mg was associated with an incremental cost-effectiveness ratio (ICER) of EUR 1339 per QALY gained versus empagliflozin and was considered dominant (clinically superior and cost saving) versus sitagliptin and liraglutide. Additional analyses demonstrated that oral semaglutide 7 mg was associated with improvements of 0.11 QALYs and increased costs of EUR 226 versus sitagliptin and was therefore associated with an ICER of EUR 2011 per QALY gained.. Oral semaglutide 14 mg was dominant versus sitagliptin and liraglutide, and cost-effective versus empagliflozin, for the treatment of type 2 diabetes in Spain.

Topics: Administration, Oral; Benzhydryl Compounds; Clinical Trials as Topic; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Glucagon-Like Peptides; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Liraglutide; Sitagliptin Phosphate; Spain

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown.. We pooled data (n = 148) from three randomized trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison with sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies, on accelerometer-assessed physical activity.. Liraglutide (mean -1,144 steps/day; 95% CI -2,069 to -220), empagliflozin (-1,132 steps/day; -1,739, -524), and sitagliptin (-852 steps/day; -1,625, -78) resulted in reduced total daily physical activity after 6 months (P < 0.01 vs. control). Moderate- to vigorous-intensity physical activity was also reduced. Dietary interventions led to no change or an increase in physical activity.. The initiation of all glucose-lowering therapies was associated with reduced physical activity, warranting further investigation.

Topics: Dipeptidyl-Peptidase IV Inhibitors; Exercise; Glucagon-Like Peptide-1 Receptor; Glucose; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Liraglutide; Randomized Controlled Trials as Topic; Sitagliptin Phosphate

The effect of sodium glucose cotransporter 2 inhibitors (SGLT2i) on the total (first and recurrent) burden of cardiovascular (CV) hospitalizations, including hospitalization for heart failure, myocardial infarction, and stroke, is poorly understood.. To assess the effect of empagliflozin, an SGLT2i, on total CV hospitalizations among older adults with T2D.. Using data from Medicare fee-for-service (08/2014-09/2017), we identified 1:1 propensity score-matched cohorts of patients with T2D initiating empagliflozin versus sitagliptin or empagliflozin versus glucagon-like peptide-1 receptor agonists (GLP-1RA), balancing >140 baseline covariates. We compared the risk of first and recurrent hospitalizations with any CV condition as the primary discharge diagnosis (ICD-9: 390-459; ICD-10: I00-I99), hospitalizations for heart failure (HHF), and myocardial infarctions (MI) or stroke. We estimated treatment effects based on the Ghosh-Lin semiparametric model for recurrent events as primary and joint frailty model as secondary analysis.. We included 11,429 matched-pairs of empagliflozin and sitagliptin initiators and 17,502 matched-pairs of empagliflozin and GLP1-RA initiators with an average age of 72 years. Empagliflozin was associated with a reduced risk of total CV hospitalizations (0.80 [0.69-0.93] vs sitagliptin; 0.88 [0.77-1.00] vs GLP-1RA) and total HHF (0.70 [0.51-0.98] vs sitagliptin; 0.76 [0.56-1.03] vs GLP1-RA) over a mean follow up of 6.3 months. No differences between treatments were observed for MI or stroke. Results were consistent for joint frailty models.. Empagliflozin, compared to sitagliptin or to a lesser extent GLP1-RA, was associated with a reduction in the burden of total CV hospitalizations and HHF in older patients with T2D.

Topics: Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypoglycemic Agents; Medicare; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Stroke; United States

Management of diabetes during fasting is a clinical challenge. Sodium glucose co-transporter -2 inhibitors (SGLT2i) are considered safe with a low risk of hypoglycemia. However, studies on SGLT2i are scarce. This study was designed to compare the efficacy, safety, and tolerability of empagliflozin with metformin during Ramadan in comparison with sitagliptin and metformin.. It was a prospective, observational study, conducted at 11 different sites all across Pakistan on an outpatient basis during Ramadan (May 2021-June 2021). including 132 patients, 88 who received metformin and sitagliptin, and 44 patients who received metformin and empagliflozin.. Patients of the SGLT-2i group experienced similar symptomatic hypoglycemic episodes (15.9%) as the sitagliptin group. There was an improvement in blood sugar levels after the use of SGLT-2i (RBS 181 ± 64 before Ramadan vs 162 ± 53 after Ramadan). HbA1c also improved after the use of SGLT-2i before and after Ramadan (7.2 ± 0.8 vs 6.9 ± 0.9 for Metformin + Empagliflozin and 7.8 ± 1.5 vs 7.6 ± 1.6 for Metformin and sitagliptin). Weight and BMI improved after the use of SGLT-2i (BMI 36.5 ± 4.8 before Ramadan and 33.7 ± 2.4 after Ramadan). There were no reported cases of urinary tract infection in the empagliflozin group.. SGLT-2 inhibitors combined with metformin for patients with diabetes during Ramadan fasting is as effective, safe and well tolerated as DPP4 combined with metformin.

Topics: Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Drug Therapy, Combination; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Metformin; Prospective Studies; Sitagliptin Phosphate; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters

Limited evidence is available on the comparative effectiveness of empagliflozin vs alternative second-line glucose-lowering agents in patients with type 2 diabetes (T2D) receiving routine care who have a broad spectrum of cardiorenal risk.. To evaluate the association of empagliflozin with cardiovascular outcomes relative to liraglutide and sitagliptin, stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD).. This retrospective comparative effectiveness cohort study used deidentified Medicare claims data from August 1, 2014, to September 30, 2018, with follow-up from drug initiation until treatment changes, death, or gap in Medicare enrollment (>30 days). Data analysis was performed from October 1, 2021, to April 30, 2022. Medicare fee-for-service beneficiaries older than 65 years with T2D were included. A total of 45 788 patients (22 894 propensity score-matched pairs initiating treatment with either empagliflozin or liraglutide) were included in cohort 1, and 45 624 patients (22 812 propensity score-matched pairs initiating treatment with either empagliflozin or sitagliptin) were included in cohort 2.. Empagliflozin vs liraglutide (cohort 1) or empagliflozin vs sitagliptin (cohort 2).. Primary outcomes were (1) modified major adverse cardiovascular events (MACEs), including a composite of myocardial infarction, stroke, and all-cause mortality, and (2) hospitalization for heart failure (HHF). Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, adjusting for 143 baseline covariates using 1:1 propensity score matching.. Among 45 788 patients in cohort 1, the mean (SD) age was 71.9 (5.1) years; 23 396 patients (51.1%) were female, 22 392 (48.9%) were male, and 38 049 (83.1%) were White. Among 45 624 patients in cohort 2, the mean (SD) age was 72.1 (5.1) years; 21 418 patients (46.9%) were female, 24 206 (53.1%) were male, and 37 814 (82.9%) were White. Relative to patients initiating liraglutide, those initiating empagliflozin had a similar risk of the modified MACE outcome (HR, 0.90; 95% CI, 0.79-1.03) and a reduced risk of HHF (HR, 0.66; 95% CI, 0.52-0.82). Across subgroups, empagliflozin was associated with a lower risk of the modified MACE outcome in patients with a history of ASCVD (HR, 0.83; 95% CI, 0.71-0.98) and HF (HR, 0.77; 95% CI, 0.60-1.00) compared with liraglutide, and potential heterogeneity in estimates was observed by sex (male: HR, 0.85 [95% CI, 0.71-1.01]; female: HR, 1.16 [95% CI, 0.94-1.42]; P = .02 for homogeneity). However, reductions in the risk of HHF were observed across most subgroups (eg, ASCVD: HR, 0.66 [95% CI, 0.51-0.85]; HF: HR, 0.66 [95% CI, 0.49-0.88]). Compared with sitagliptin, empagliflozin was associated with reduced risks of the modified MACE outcome (HR, 0.68; 95% CI, 0.60-0.77) and HHF (HR, 0.45; 95% CI, 0.36-0.56), which were consistent across all subgroups. Absolute benefits of empagliflozin vs sitagliptin were larger in patients with a history of ASCVD (modified MACE: RD, -17.6 [95% CI, -24.9 to -10.4]; HHF: RD, -16.7 [95% CI, -21.7 to -11.9]), HF (modified MACE: RD, -41.1 [95% CI, -59.9 to -22.6]; HHF: RD, -50.4 [95% CI, -67.5 to -33.9]), or CKD (modified MACE: RD, -26.7 [95% CI, -41.3 to -12.3]; HHF: RD, -31.9 [95% CI, -43.5 to -20.8]).. In this comparative effectiveness study of older adults, empagliflozin was associated with a lower risk of HHF (relative to both liraglutide and sitagliptin) and the modified MACE outcome (relative to sitagliptin), with larger absolute benefits in patients with established cardiorenal diseases. These findings suggest that older adults with T2D might benefit more from empagliflozin vs liraglutide or sitagliptin with respect to the risk of HHF; with respect to the risk of MACEs, empagliflozin might be preferable to liraglutide only in patients with cardiovascular disease history and to sitagliptin across all patient subgroups.

Topics: Aged; Atherosclerosis; Cohort Studies; Diabetes Mellitus, Type 2; Female; Glucose; Heart Failure; Humans; Hypoglycemic Agents; Liraglutide; Male; Medicare; Myocardial Infarction; Renal Insufficiency, Chronic; Retrospective Studies; Sitagliptin Phosphate; United States

To estimate the cost-effectiveness of sequential addition of empagliflozin versus sitagliptin after metformin in patients with type 2 diabetes (T2D) with or without cardiovascular disease (CVD) from the perspective of the US healthcare payer.. An individual simulation model predicted lifetime diabetes-related complications, using UKPDS-OM2 equations in patients without CVD, and EMPA-REG OUTCOME equations in patients with CVD. Additional US-based sources informed inputs for population characteristics, adverse events, non-CV death, treatment escalation, quality of life and costs. Costs and quality-adjusted life-years (QALYs) were discounted 3.0% annually.. The incremental cost-effectiveness ratio (ICER) for second-line empagliflozin versus sitagliptin in the overall T2D population was $6967/QALY. Empagliflozin led to longer CVD-free survival (0.07 years) and an 11% reduction in CV death in patients with CVD compared with sitagliptin. Empagliflozin resulted in greater benefits with greater costs in patients with versus without baseline CVD, yielding ICERs of $3589/QALY versus $12 577/QALY, respectively. Results were consistent across a range of deterministic and probabilistic sensitivity analyses and scenarios.. Compared with sitagliptin, empagliflozin was cost-effective (at $50 000/QALY US threshold) as a second-line treatment to metformin for T2D patients with or without CVD in the United States. Our findings lend additional support for more widespread adoption of guidelines by healthcare decision-makers for T2D treatment.

Topics: Benzhydryl Compounds; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Glucosides; Humans; Hypoglycemic Agents; Quality of Life; Quality-Adjusted Life Years; Sitagliptin Phosphate; United States

Topics: Administration, Oral; Benzhydryl Compounds; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Costs; Glucagon-Like Peptides; Glucosides; Humans; Hypoglycemic Agents; Liraglutide; Sitagliptin Phosphate; United States

Sodium-glucose co-transporter 2 inhibitors reduce the risk of cardiovascular events in type 2 diabetic patients with coronary artery disease (CAD); however, the underlying mechanisms remain unclear.. We compared the effects of empagliflozin vs. sitagliptin therapy on myocardial perfusion reserve (MPR) using dynamic single-photon emission computed tomography (SPECT) imaging.. In total, 100 patients with type 2 diabetes, CAD and an MPR <2.5 were randomized to receive either empagliflozin (10 mg once daily) or sitagliptin (100 mg once daily). Dynamic SPECT examinations were performed at baseline and at 6 months. The primary endpoint was the percent change of global MPR. Evaluable SPECT data were available for 98 patients.. Baseline clinical characteristics and SPECT data were well balanced between the two groups. At a 6-month follow-up, the fasting glucose and glycated hemoglobin levels significantly decreased in both groups. Hematocrit and hemoglobin levels significantly increased in the empagliflozin group but not in the sitagliptin group. The global MPR significantly improved after treatment in both groups (34.5 ± 70.6%; P = 0.005 for empagliflozin vs. 22.4 ± 45.7%; P = 0.024 for sitagliptin). However, there was no significant difference in the global MPR between the two groups (P = 0.934). Similar findings were detected with regard to the regional MPR.. Among patients with type 2 diabetes and CAD, both empagliflozin and sitagliptin significantly improved the global MPR with no significant difference between the groups.

Topics: Benzhydryl Compounds; Coronary Artery Disease; Glucosides; Humans; Middle Aged; Myocardial Perfusion Imaging; Sitagliptin Phosphate; Tomography, Emission-Computed, Single-Photon

Early-onset adult type 2 diabetes (diagnosed between ages 18 and 39 years) is increasingly prevalent and associated with poor long-term outcomes. We hypothesised that individuals with early-onset adult type 2 diabetes were underrepresented in the prominent research trials that underpin type 2 diabetes management guidelines.. We reviewed the mean age of the study populations recruited to 90 prominent trials in type 2 diabetes, including 37 cardio-renal outcomes trials across a range of pharmacological, non-pharmacological and multifactorial interventions, 28 trials from the phase III programmes of three representative glucose-lowering therapies used routinely in clinical practice (empagliflozin, liraglutide and sitagliptin) and 25 prominent trials of diabetes self-management education and support or intensive lifestyle interventions (diet or supervised exercise training). We then estimated the number of individuals within these trials who were aged between 18 and 39 years.. Across all 90 trials, the mean age of 268,978 participants was 63 years (range 51-69 years in individual trials). In 73 trials (81%), <5% of participants were estimated to be aged 18-39 years, despite this age group representing ~15-20% of the adult type 2 diabetes population. Twenty-nine of these trials (32%; total 164,953 participants) excluded individuals below 40 years of age altogether.. Guidelines for early-onset adult type 2 diabetes are extrapolated predominantly from evidence in older individuals. Strategies to support the participation of individuals with early-onset adult type 2 diabetes in future research are imperative to ensure guidelines for these high-risk individuals are evidence-based.

Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Liraglutide; Male; Middle Aged; Sitagliptin Phosphate; Young Adult

Oral semaglutide is the first orally administered glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes, and has been evaluated in the PIONEER clinical trial program. These trials assessed the proportions of patients achieving single and composite endpoints, encompassing glycemic control [defined in terms of glycated hemoglobin (HbA1c)], weight loss, and hypoglycemia. The present study assessed the cost of control with oral semaglutide versus empagliflozin, sitagliptin, and liraglutide in the US.. Four endpoints were evaluated: (1) HbA1c ≤ 6.5%; (2) HbA1c < 7.0%; (3) ≥ 1.0%-point HbA1c reduction and weight loss ≥ 3.0%; and (4) HbA1c < 7.0% without hypoglycemia and without weight gain. The proportions of patients achieving each endpoint were sourced from the PIONEER 2, 3 and 4 trials. Treatment costs were accounted over an annual time-period in 2019 US dollars (USD), based on wholesale acquisition cost. Cost of control was calculated by dividing treatment costs by the proportion of patients achieving each target.. Oral semaglutide was consistently associated with the lowest cost of control for all four endpoints. For the targets of HbA1c ≤ 6.5% and HbA1c < 7.0%, oral semaglutide 14 mg was associated with lower cost of control than empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg by USD 15,036, 14,697, and 6996, respectively, and USD 931, 346 and 4497, respectively. For the double composite endpoint, cost of control was lower with oral semaglutide 14 mg by USD 525, 32,277 and 13,011, respectively versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg. For the triple composite endpoint, cost of control was lower with oral semaglutide 14 mg by USD 1255, 7510 and 5774, respectively.. Oral semaglutide was associated with lower cost of bringing patients with type 2 diabetes to four clinically-relevant treatment targets versus empagliflozin, sitagliptin, and liraglutide in the US.. Novo Nordisk A/S.

Topics: Benzhydryl Compounds; Blood Glucose; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Glucagon-Like Peptides; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Liraglutide; Middle Aged; Sitagliptin Phosphate; United States; Weight Loss

The EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 diabetes Mellitus Patients) showed that empagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces the risk of hospitalization for heart failure (HHF) by 35%, on top of standard of care in patients with type 2 diabetes mellitus (T2D) and established cardiovascular disease. The EMPRISE (Empagliflozin Comparative Effectiveness and Safety) study aims to assess empagliflozin's effectiveness, safety, and healthcare utilization in routine care from August 2014 through September 2019. In this first interim analysis, we investigated the risk of HHF among T2D patients initiating empagliflozin versus sitagliptin, a dipeptidyl peptidase-4 inhibitor.. Within 2 commercial and 1 federal (Medicare) claims data sources in the United States, we identified a 1:1 propensity score-matched cohort of T2D patients ≥18 years old initiating empagliflozin or sitagliptin from August 2014 through September 2016. The HHF outcome was defined as a HF discharge diagnosis in the primary position (HHF-specific); a broader definition was based on a HF discharge diagnosis in any position (HHF-broad). Hazard ratios (HRs) and 95% CIs were estimated controlling for over 140 baseline characteristics in each data source and pooled by fixed-effects meta-analysis.. After propensity-score matching, we identified 16,443 patient pairs who initiated empagliflozin or sitagliptin. Average age was approximately 59 years, almost 54% of the participants were males, and approximately 25% had records of existing cardiovascular disease. Compared with sitagliptin, the initiation of empagliflozin decreased the risk of HHF-specific by 50% (HR, 0.50; 95% CI, 0.28-0.91), and the risk of HHF-broad by 49% (HR, 0.51;95% CI, 0.39-0.68), over a mean follow-up of 5.3 months. The results were consistent in patients with and without baseline cardiovascular disease, and for empagliflozin at both the 10- and 25-mg daily doses; analyses comparing empagliflozin versus the dipeptidyl peptidase-4 inhibitor class, and comparing sodium-glucose cotransporter-2 inhibitor versus dipeptidyl peptidase-4 inhibitor classes also produced consistent findings.. The first interim analysis from EMPRISE showed that compared with sitagliptin, the initiation of empagliflozin was associated with a decreased risk of HHF among patients with T2D as treated in routine care, with and without a history of cardiovascular disease.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT03363464.

Topics: Aged; Benzhydryl Compounds; Comparative Effectiveness Research; Databases, Factual; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glucosides; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Risk Assessment; Risk Factors; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome; United States

Cardiovascular protection following empagliflozin therapy is not entirely attributable to the glucose lowering effect. Increased hematocrit might influence the shear stress that is the main force acting on the endothelium, regulating its anti-atherogenic function.. We designed the study with the aim of investigating the effect of empagliflozin on blood viscosity and shear stress in the carotid arteries. A secondary endpoint was the effect of empagliflozin on carotid artery wall thickness.. The study was a non-randomized, open, prospective cohort study including 35 type 2 diabetic outpatients who were offered empagliflozin or incretin-based therapy (7 liraglutide, 8 sitagliptin) in combination with insulin and metformin. Blood viscosity, shear stress and carotid wall thickness were measured at baseline and at 1 and 3 months of treatment. Blood viscosity was measured with a viscometer, and shear stress was calculated using a validated formula. Intima-media thickness (IMT) of the carotid artery was detected by ultrasound and was measured with dedicated software.. Blood viscosity (4.87 ± 0.57 vs 5.32 ± 0.66 cP, p < 0.02) and shear stress significantly increased in the Empagliflozin group while no change was detected in the Control group (4.66 ± 0.56 vs 4.98 ± 0.73 cP, p = NS). IMT significantly decreased in the Empagliflozin group after 1 and 3 months (baseline: 831 ± 156, 1-month 793 ± 150, 3-month 766 ± 127 μm; p < 0.0001), while in the liraglutide group, IMT significantly decreased only after 3 months (baseline 879 ± 120; 1-month 861 ± 163; 3-month 802 ± 114 μm; p < 0.001). In the sitagliptin group, IMT remained almost unchanged (baseline 901 ± 135; 1-month 902 ± 129; 3-month 880 ± 140 μm; p = NS).. This study is the first to describe a direct effect of empagliflozin on blood viscosity and wall shear stress. Furthermore, IMT was markedly reduced early on in the Empagliflozin group.

Topics: Aged; Benzhydryl Compounds; Blood Viscosity; Carotid Artery, Common; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Female; Glucosides; Humans; Incretins; Liraglutide; Male; Middle Aged; Prospective Studies; Regional Blood Flow; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Stress, Mechanical; Time Factors; Treatment Outcome

Diabetic ketoacidosis has been described as a rare complication of acromegaly and may be observed in 1% of affected patients. The well-described direct lipolytic effect of growth hormone results in increased availability of free fatty acids (FFAs) for hepatic ketogenesis and is an important pathogenic event. More recently, ketoacidosis has been identified as an important complication of sodium-glucose-transport-protein 2 inhibitors (SGLT2i). Increased pancreatic glucagon secretion, impaired renal ketone body clearance, and an increase in FFA concentrations secondary to decreased insulin concentrations are likely precipitating factors.. We report a case of rapid-onset severe ketoacidosis within 2 days after adding empagliflozin to metformin, sitagliptin, and gliclazide in a presumably type 2 diabetic patient with unrecognized acromegaly and chronic hyperglycemia. Transsphenoidal resection of the growth-hormone secreting macroadenoma restored normal growth-hormone and insulinlike growth factor 1 concentrations and the diabetes was well controlled thereafter.. We hypothesize that SGLT2i, through their intrinsic effects on ketone body metabolism, may possibly precipitate ketoacidosis in patients with active acromegaly and diabetes mellitus.

Topics: Adenoma; Benzhydryl Compounds; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Drug Therapy, Combination; Fatty Acids, Nonesterified; Gliclazide; Glucagon; Glucosides; Growth Hormone-Secreting Pituitary Adenoma; Humans; Hypoglycemic Agents; Insulin; Ketone Bodies; Male; Metformin; Middle Aged; Severity of Illness Index; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors

Topics: Adamantane; Benzhydryl Compounds; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Glucosides; Humans; Hypoglycemic Agents; Liraglutide; Peptides; Piperidines; Risk; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Uracil

Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Female; Glucosides; Humans; Male; Pyrazines; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Triazoles