Drugs stimulating insulin secretion in early clinical development for the treatment of type 1 diabetes: what's new?

Introduction: Type 1 diabetes is a chronic autoimmune condition characterized by the selective destruction of insulin-producing beta cells in the pancreas. The etiology of T1D is multifactorial, with a combination of genetic susceptibility and environmental triggers believed to underlie beta-cell destruction. Preserving and prolonging beta-cell function in T1D is a pivotal therapeutic objective that can mitigate disease progression and improve glycemic control.

Evaluating semaglutide + LAI-287 (IcoSema) for the treatment of diabetes mellitus type II.

Introduction: A stepwise coordinated multiple therapeutic targeted approach to the treatment of type 2 diabetes includes starting with lifestyle modification, oral antihyperglycemic agents, non-insulin injectables (Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and both short and long-acting insulins. Ultra-long-acting insulins offer more convenient administration. As in any chronic disease, the introduction of a novel medication must balance safety, efficacy, financial cost, as well as improved patient convenience and adherence.

Assessing the therapeutic and toxicological profile of novel GLP-1 receptor agonists for type 2 diabetes.

Introduction: GLP-1 receptor agonists provide multiple benefits for patients with type 2 diabetes. Nonetheless, there are also several significant adverse effects associated with these agents. A thorough understanding of both therapeutic and toxicological profiles of GLP-1 receptor agonists is crucial for appropriate utilization of this medication class.

Type 1 diabetes: key drug targets and how they could influence future therapeutics.

Introduction: Despite significant strides made in the management of T1DM, standard management is still insulin analog therapy. Some non-insulin therapies traditionally reserved for the treatment of T2DM have been explored in caring for patients with T1DM, and pancreas transplant is an option for few. However, T1DM remains a challenging disease to manage, encouraging development of novel pharmacologic agents.

Emerging drugs for the treatment of diabetic nephropathy.

Introduction: Diabetic nephropathy remains a significant economic and social burden on both the individual patient and health-care systems as the prevalence of diabetes increases in the general population. The complex pathophysiology of diabetic kidney disease poses a challenge in the development of effective medical treatments for the disease. However, the multiple facets of diabetic nephropathy also offer a variety of potential strategies to manage this condition.

The role of Recent Pharmacotherapeutic Options on the Management of Treatment Resistant Type 2 Diabetes.

Introduction: Type 2 diabetes mellitus is a complex progressive disease leading to chronic hyperglycemia due to insulin resistance and pancreatic beta-cell failure. Intensification of treatment regimens is often necessary due to the overall decline in insulin secretion. Unfortunately, many patients are unable to achieve optimal glycemic control despite the standard of care and thus may be classified as 'treatment resistant'.

Nocturnal hypoglycemia in type 1 and type 2 diabetes: an update on prevalence, prevention, pathophysiology and patient awareness.

Introduction: Despite considerable progress in diabetes treatment, prevalence of nocturnal hypoglycemia in type 1 diabetes mellitus (T1DM) and advanced insulin treated type 2 diabetes mellitus (T2DM) remains high.

Areas Covered: The present manuscript describes the prevalence of night-time hypoglycemia as reported in observational and randomized controlled trials. Factors that affect the risk of hypoglycemia are highlighted.

Sodium-glucose cotransporter 2 inhibitors for the management of type 2 diabetes.

Introduction: Sodium-glucose cotransporter (SGLT) 2 inhibitors reduce glucose reabsorption in the kidney, increase glucosuria, and improve glycemia. Besides glycemic efficacy, the class also lowers risk of cardiovascular and renal disease.

Areas Covered: The authors describe late phase trials of empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin.

Update on the effects of GLP-1 receptor agonists for the treatment of polycystic ovary syndrome.

: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) offer a unique opportunity to simultaneously address various comorbid associated conditions and phenotypic presentations of polycystic ovary syndrome (PCOS) as these agents improve insulin sensitivity, reduce cardiovascular disease (CVD) risk, result in weight loss, and improve nonalcoholic fatty liver disease.: The authors describe trials conducted during the last 5 years and provide an update on exenatide and liraglutide use in PCOS women. Information from the studies investigating GLP-1 RAs effects on reducing CVD risk in PCOS is also presented.

Effects of anti-diabetic treatments in type 2 diabetes and fatty liver disease.

: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are significant non-communicable diseases that often affect individuals concurrently. In individuals with both T2DM and NAFLD, there is evidence that anti-diabetic therapies may demonstrate potential combined beneficial metabolic and reduced hepatic inflammatory effects.: A PubMed and Google Scholar search was performed to find relevant literature.

Considerations when using alpha-glucosidase inhibitors in the treatment of type 2 diabetes.

: Alpha-glucosidase inhibitors (AGIs) - oral antihyperglycemic drugs, inhibit upper gastrointestinal enzymes that break down complex carbohydrates into glucose. As a result, the absorption of glucose is delayed, postprandial glucose reduced, and glycemic control improved.: In this review, the authors describe the current recommendations on the use of the three major approved AGIs (acarbose, miglitol, voglibose).

An update on the safety and efficacy of oral antidiabetic drugs: DPP-4 inhibitors and SGLT-2 inhibitors.

Introduction: Oral antidiabetic medications are important in many type 2 diabetes care plans.

Areas Covered: The article summarizes the cardiovascular and renal safety data for DPP-4 inhibitors and SGLT-2 inhibitors and specific safety data particular to each class.

Expert Opinion: DPP-4 and SGLT-2 inhibitors provide unique anti-hyperglycemic mechanisms.

Using DPP-4 inhibitors to modulate beta cell function in type 1 diabetes and in the treatment of diabetic kidney disease.

Introduction: DPP-4 inhibitors have pleomorphic effects that extend beyond the anti-hyperglycemic labeled use of the drug. DPP-4 inhibitors have demonstrated promising renal protective effects in T2DM and T1DM and protective effects against immune destruction of pancreatic beta-cells in T1DM.

Areas Covered: The efficacy of DPP-4 inhibitors in the treatment of diabetic kidney disease and possible adjunct with insulin in the treatment of T1DM to preserve beta-cell function.

Oral semaglutide for the treatment of type 2 diabetes.

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.

Effects of Severe Hypoglycemia on Cardiovascular Outcomes and Death in the Veterans Affairs Diabetes Trial.

Objective: To determine the risk factors for severe hypoglycemia and the association between severe hypoglycemia and serious cardiovascular adverse events and cardiovascular and all-cause mortality in the Veterans Affairs Diabetes Trial (VADT).

Research Design And Methods: This post hoc analysis of data from the VADT included 1,791 military veterans (age 60.5 ± 9.

Peroxisome proliferator-activated receptor alpha-mediated drug toxicity in the liver.

Drug-induced hepatic injury is the most common cause of acute liver failure in the United States. Peroxisome proliferator-activated receptor alpha (PPARα)-mediated drugs are included among the approximately 900 natural and synthetic substances, which have shown hepatotoxicity. Areas covered: This review will focus on fibrates - PPARα agonists and their implication in causing liver injury.

Subcutaneous semaglutide (NN9535) for the treatment of type 2 diabetes.

It is critical for individuals with type 2 diabetes mellitus (T2DM) to maintain optimal glycemia while avoiding hypoglycemia, control body weight, and reduce cardiovascular risk. The GLP-1 receptor agonists stimulate glucose-dependent insulin release (low risk of hypoglycemia), inhibit glucagon secretion, slow gastric emptying and suppress appetite (weight loss). The new members of the class are available as once daily or weekly injections.

Understanding the impact of hypoglycemia on the cardiovascular system.

Introduction: Hypoglycemia occurs commonly in insulin requiring individuals with either Type 1 or Type 2 Diabetes.

Areas Covered: This article will review recent information on the pro-inflammatory and pro-atherothrombotic effects of hypoglycemia. Additionally, effects of hypoglycemia on arrhythmogenic potential and arterial endothelial dysfunction will be discussed.

The care of pregestational and gestational diabetes and drug metabolism considerations.

Normal pregnancy development involves gradual decline in insulin sensitivity, which sometimes requires pharmacotherapy. Insulin is the drug of choice for gestational and pregestational diabetes. Metabolism of traditional insulins results in inadequate onset and duration of action and marked peak activity.

GLP-1 receptor agonists in the treatment of polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) affects many women of child-bearing age and is characterized by hyperandrogenism, ovulatory and metabolic dysfunction. A primary treatment goal is weight reduction. The weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to PCOS patients.

Discontinued drug therapies to treat diabetes in 2015.

This manuscript describes 21 drug targets in the area of diabetes and related conditions that were discontinued in 2015. Areas covered: The material for this paper was obtained by contacting biopharmaceutical companies, reviewing their pipelines, press releases and annual reports. Additionally, the authors searched clinicaltrials.