[Drug therapy of type-2-diabetes-is metformin dispensable now?].

Metformin has been recommended as first-line pharmacological therapy in type‑2 diabetes (T2D) since 1998. It was the first medication that demonstrated cardiovascular benefits in obese subjects with T2D. Efficacy and safety of metformin have since been demonstrated in further studies and in real-world data on its use in practice.

[Gastrointestinal hormones: their increasing pharmacotherapeutic relevance in metabolic diseases].

Gastrointestinal hormones play an important role in the endocrine communication between the intestine, the pancreas, the liver and the brain. Glucagon-like peptide‑1 receptor agonists (GLP-1RA) are established therapeutic agents in the treatment of type‑2 diabetes. Multiple agonists acting as ligands on various gastrointestinal hormone receptors are a novel pharmacological development.

Clinical perspectives on the use of the GIP/GLP-1 receptor agonist tirzepatide for the treatment of type-2 diabetes and obesity.

Incretin-based therapies with glucagon-like peptide-1 receptor agonists (GLP-1RA) are already established in the treatment of type 2 diabetes (T2D). The development of novel dual- or triple-receptor agonists that bind to the receptors not only for GLP-1 but also to the receptors for glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon is intended to address different metabolic pathways for carbohydrate, lipid, and protein metabolism simultaneously. Dual- and triple-receptor agonists acting different receptors and postreceptor pathways seem attractive in view of potentially additive or synergistic effects in the treatment of T2D and obesity.

Obesity and Impaired Metabolic Health Increase Risk of COVID-19-Related Mortality in Young and Middle-Aged Adults to the Level Observed in Older People: The LEOSS Registry.

Advanced age, followed by male sex, by far poses the greatest risk for severe COVID-19. An unresolved question is the extent to which modifiable comorbidities increase the risk of COVID-19-related mortality among younger patients, in whom COVID-19-related hospitalization strongly increased in 2021. A total of 3,163 patients with SARS-COV-2 diagnosis in the Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort were studied.

The incretin/glucagon system as a target for pharmacotherapy of obesity.

Obesity is a chronic, multifactorial, relapsing disease. Despite multicomponent lifestyle interventions, including pharmacotherapy, maintaining bodyweight loss is challenging for many people. The pathophysiology of obesity is complex, and currently approved pharmacotherapies only target a few of the many pathways involved; thus, single-targeting agents have limited efficacy.

Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide.

Early and effective glycemic control can prevent or delay the complications associated with type 2 diabetes (T2D). The benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming increasingly recognized and they now feature prominently in international T2D treatment recommendations and guidelines across the disease continuum. However, despite providing effective glycemic control, weight loss, and a low risk of hypoglycemia, GLP-1RAs are currently underutilized in clinical practice.

Considering Insulin Secretory Capacity as Measured by a Fasting C-Peptide/Glucose Ratio in Selecting Glucose-Lowering Medications.

Type 2 diabetes mellitus is a heterogeneous disease. Recently introduced new subclassifications promise more efficacious, tailored treatments which could complement current guidelines. In the differentiation of the new diabetes subphenotypes, assessment of insulin secretion is one of the essential components.

Clinical Use of DPP-4 Inhibitors.

DPP-4 inhibitors were introduced for the treatment of type 2 diabetes in 2006. They stimulate insulin secretion and inhibit glucagon secretion by elevating endogenous GLP-1 concentrations without an intrinsic hypoglycaemia risk. Their efficacy potential to lower HbA1c is in the range between 0.

The Cardiovascular Benefits Associated with the Use of Sodium-Glucose Cotransporter 2 Inhibitors - Real-World Data.

Type 2 diabetes (T2D) is associated with numerous comorbidities that significantly reduce quality of life, increase mortality and complicate treatment decisions. In a recent cardiovascular outcomes trial, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME), the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin was shown to reduce cardiovascular (CV) mortality and heart failure in high-risk patients with T2D with a previous CV event or with established CV disease (CVD). Recently published data from the Canagliflozin Cardiovascular Assessment Study (CANVAS-PROGRAM) study suggested that the cardiovascular benefits of empagliflozin are also seen with the SGLT2-inhibitor canagliflozin, indicating a class effect of SGLT2 inhibitors.

Efficacy and safety of MK-1293 insulin glargine compared with originator insulin glargine (Lantus) in type 1 diabetes: A randomized, open-label clinical trial.

Aim: To compare the efficacy and safety of MK-1293 insulin glargine (Mk-Gla; 100 U/mL) with originator insulin glargine, Lantus (Sa-Gla), in people with type 1 diabetes mellitus (T1DM).

Materials And Methods: This phase 3, randomized, active-controlled, open-label, 52-week study (ClinicalTrials.gov NCT02059161) enrolled 508 people with T1DM (HbA1c ≤11.

Efficacy and safety of MK-1293 insulin glargine compared with originator insulin glargine (Lantus) in type 2 diabetes: A randomized, open-label clinical trial.

Aim: To compare the efficacy and safety of MK-1293 insulin glargine (Mk-Gla) and Lantus (Sa-Gla) in people with type 2 diabetes mellitus (T2DM).

Materials And Methods: This Phase 3, randomized, active-controlled, open-label, 24-week clinical trial (ClinicalTrials.gov number NCT02059187) enrolled 531 participants with T2DM (HbA1c ≤11.

A safety evaluation of empagliflozin plus linagliptin for treating type 2 diabetes.

Dipeptidyl-peptidase-IV inhibitors (DPP-4i) and sodium-glucose-transporter-2 inhibitors (SGLT-2i) are oral antidiabetic drugs that improve glycemic parameters and possess a very low intrinsic hypoglycemia risk and favorable cardiovascular data. Areas covered: An overview on the clinical studies investigating the combination therapy with the DPP-4i linagliptin and the SGLT-2i empagliflozin is given. The clinical evidence for the efficacy and safety of free combinations as well as for their fixed dose combinations is presented.

Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: Subgroup analysis of a randomized clinical trial.

Aims/introduction: Type 2 diabetes mellitus is an epidemic in Asia, yet clinical trials of glucose-lowering therapies often enroll predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in newly diagnosed type 2 diabetes mellitus patients in Asia with marked hyperglycemia.

Materials And Methods: This was a post-hoc subgroup analysis of a multinational, parallel-group clinical trial in which 316 newly diagnosed type 2 diabetes mellitus patients with glycated hemoglobin A1c (HbA1c) 8.

Effect of once-weekly dulaglutide on glycated haemoglobin (HbA1c) and fasting blood glucose in patient subpopulations by gender, duration of diabetes and baseline HbA1c.

Aims: To evaluate the efficacy and safety of dulaglutide 1.5 and 0.75 mg in patients with type 2 diabetes by subgroups of gender, duration of diabetes and baseline glycated haemoglobin (HbA1c) in the dulaglutide clinical development programme (AWARD-1 to -6 and -8 clinical trials).

DPP4 gene variation affects GLP-1 secretion, insulin secretion, and glucose tolerance in humans with high body adiposity.

Objective: Dipeptidyl-peptidase 4 (DPP-4) cleaves and inactivates the insulinotropic hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide, collectively termed incretins. DPP-4 inhibitors entered clinical practice as approved therapeutics for type-2 diabetes in 2006. However, inter-individual variance in the responsiveness to DPP-4 inhibitors was reported.

Variability in and predictors of glycaemic responses after 24 weeks of treatment with exenatide twice daily and exenatide once weekly.

The range of glycated haemoglobin (HbA1c) responses and characteristics associated with above-average response to exenatide twice daily and once weekly were examined. Data were pooled from 8 exenatide-twice-daily and 5 exenatide-once-weekly studies. A baseline HbA1c-corrected measure of change in HbA1c after 24 weeks identified high, average and low responses.

Nonsuppressed Glucagon After Glucose Challenge as a Potential Predictor for Glucose Tolerance.

Glucagon levels are classically suppressed after glucose challenge. It is still not clear as to whether a lack of suppression contributes to hyperglycemia and thus to the development of diabetes. We investigated the association of postchallenge change in glucagon during oral glucose tolerance tests (OGTTs), hypothesizing that higher postchallenge glucagon levels are observed in subjects with impaired glucose tolerance (IGT).

Linagliptin as add-on to empagliflozin and metformin in patients with type 2 diabetes: Two 24-week randomized, double-blind, double-dummy, parallel-group trials.

Aim: To evaluate the efficacy and safety of linagliptin vs placebo as add-on to empagliflozin and metformin in patients with type 2 diabetes.

Materials And Methods: Patients with inadequate glycaemic control despite stable-dose metformin received open-label empagliflozin 10 mg (study 1) or 25 mg (study 2) as add-on therapy for 16 weeks. Subsequently, those with HbA1c ≥7.