Increased cost of illness among European patients with type 2 diabetes treated with insulin

Objectives: To investigate the association between outcomes and different escalating combinations of non-insulin medications vs. insulin.

Methods: Data were taken from the 2013 5EU NHWS, a cross-sectional survey including 62,000 respondents across France, Germany, Italy, Spain, and the UK. Costs were estimated from self-reported work impairment and healthcare visits using average wages and unit costs. Respondents taking antihyperglycemic medications (n?=?2894) were compared according to treatment type using unadjusted comparisons followed by regression to adjust for confounders.

Results: Insulin users had the highest costs and worse outcomes, a pattern that remained after adjustment for a range of sociodemographic and disease characteristics. Incremental direct costs were approximately €800. Incremental indirect costs, applicable only to the employed, were larger than incremental direct costs, but were statistically significant only relative to non-insulin monotherapy.

Conclusions: Escalation using oral agents rather than insulin is associated with better quality of life and lower costs, though these relationships may not be causal. Further research is warranted on escalation using oral agents among patients for whom insulin is not required.     

Basal insulin initiation use and experience among people with type 2 diabetes mellitus with different patterns of persistence: results from a multi-national survey

Background and objective: People with type 2 diabetes mellitus (T2DM) often interrupt basal insulin treatment soon after initiation. This study aimed to describe the experiences during and after basal insulin initiation among people with T2DM with different persistence patterns.

Methods: Adults with T2DM from France, Germany, Spain, UK, US, Brazil, and Japan were identified from consumer panels for an online survey. Respondents who initiated basal insulin 3–24 months prior to survey date were categorized as continuers (no gaps of ≥7 days in insulin treatment); interrupters (first gap ≥7 days within 6 months of initiation and restarted insulin); and discontinuers (stopped insulin for ≥7 days within 6 months of initiation without restarting).

Results: Among 942 participants, continuers were older than interrupters and discontinuers (46, 37, and 38 years, respectively, p?p?Conclusion: Among people with T2DM with different persistence patterns after basal insulin initiation there were significant differences in patient characteristics and experience during and after insulin initiation. Interrupters and discontinuers more frequently reported having concerns and challenges during the initiation process, negative impacts after initiation, and less improvement in glycemic control than continuers.     

Cardiovascular safety of therapies for type 2 diabetes

Introduction: Dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP-1) analogs and sodium-glucose cotransporter 2 (SGLT2) inhibitors are relatively new therapies for the treatment of type 2 diabetes mellitus. Given the high prevalence of cardiovascular complications in patients with type 2 diabetes and recent concerns questioning CV safety of newer antidiabetic medications, cardiovascular safety of these medications requires evaluation.

Areas covered: Cardiovascular effects of these drug classes from preclinical and clinical data as well as non-cardiovascular safety issues are delineated from literature searches covering the last decade and up to June 2016. Major clinical trials assessing the cardiovascular safety of GLP-1 agonists (ELIXA and LEADER), DPP-4 inhibitors (SAVOR-TIMI 53, EXAMINE, and TECOS) and SGLT2 inhibitors (EMPA-REG OUTCOME) are reviewed and interpreted.

Expert opinion: Based on review of the present evidence, these 3 classes of antihyperglycemic therapies have acceptably safe CV safety profiles for patients with type 2 diabetes. The latest evidence from LEADER and EMPA-REG OUTCOME trials indicate that liraglutide and empagliflozin have cardiovascular benefits that may prove to be of clinical importance in the management of type 2 DM.     

Strategies to prevent type 2 diabetes

ABSTRACT

Type 2 diabetes mellitus is a public health problem of epidemic proportions and its prevalence is on the rise. The typical American born today has a one in three chance of developing type 2 diabetes. This diagnosis is associated with an adverse cardiovascular prognosis and is considered the risk equivalent of established coronary disease. Many risk factors, including the metabolic syndrome, have been implicated in its development. Even in high-risk individuals, type 2 diabetes is a preventable disease. Diet and exercise have been consistently shown to decrease the incidence of diabetes in large randomized controlled studies. Additionally, new-onset diabetes was reduced by several oral pharmacologic anti-diabetic agents including metformin, acarbose and troglitazone in randomized trials which studied patients with impaired glucose tolerance. More interestingly, multiple large prospective studies have also reported a reduction in the development of type 2 diabetes in patients treated with anti-hypertensive agents, predominantly angiotensin converting enzyme inhibitors and angiotensin receptor blockers.

In this review, we will discuss some of these important trials and the speculative mechanisms whereby those medications prevent type 2 diabetes. Such observations, if proven to be true, may represent preventive strategies which can be considered in patients with pre-diabetic conditions such as the metabolic syndrome, hypertension, impaired fasting glucose, family history of diabetes, obesity, congestive heart failure or other risks for the development of type 2 diabetes     

The power of two: an update on fixed-dose combinations for type 2 diabetes

Introduction: Patients with type 2 diabetes mellitus (T2DM) are unlikely to maintain glycemic control with monotherapy, and will eventually require therapy with multiple antihyperglycemic agents (AHAs). Combination therapy regimens with multiple AHAs may be complex and negatively impact patient adherence. Fixed-dose combinations (FDCs) are used successfully for management of numerous chronic diseases.

Areas covered: This article includes a brief overview of the add-on approach of current treatment guidelines for T2DM and reviews the evidence supporting the utility of oral FDCs in the treatment of T2DM, including recently developed oral FDCs (2010–2016). Benefits regarding safety and tolerability, adherence and cost are also discussed. Finally, the barriers limiting the use of FDCs and how these barriers may be overcome are addressed.

Expert commentary: Therapeutic strategies including FDCs need to be implemented on a larger scale. FDCs have the potential to simplify treatment regimens, improve adherence and provide long-term glycemic control.     

Time to initiation of oral antihyperglycemic and statin therapy in previously untreated patients with type 2 diabetes in the United States

Abstract

Objective:

To assess the time from the first observed diagnosis of type 2 diabetes (T2DM) to initiation of an oral antihyperglycemic agent (OAHA) and statin.     

An overview of new GLP-1 receptor agonists for type 2 diabetes

Introduction: The increasing prevalence of type 2 diabetes mellitus (T2DM) and the eventual need for multiple medications in most patients stimulated the development of new drug classes to reduce plasma glucose levels. The GLP-1 receptor agonists (GLP-1RAs) are established as an option for treatment of T2DM after metformin. They are also effective in reducing body weight but current GLP-1RAs have to be given by subcutaneous injection daily or once weekly.

Areas covered: This review focuses on the new GLP-1RAs currently undergoing development, some of which require less frequent subcutaneous administration and others that are being developed in oral formulations that may favor patient adherence.

Expert opinion: The new GLP-1RAs may have the benefit of requiring less frequent subcutaneous dosing or being active by oral administration. However, cardiovascular outcome trials have shown that DPP4 inhibitors are neutral for cardiovascular events and the first cardiovascular outcome trial with lixisenatide reported similar results, whereas the trial with the SGLT2 inhibitor empagliflozin showed a reduction in cardiovascular events. These findings in patients with high cardiovascular risk may favor the use of SGLT2 inhibitors as a second line treatment after metformin but there should still be an important role for novel GLP-1RAs, especially when weight reduction is required.     

Hypoglycemic and Antihyperglycemic Activity of Nymphaea stellata Flowers in Normal and Alloxan Diabetic Rats

Abstract

Flowers of Nymphaea stellata Willd. (Nymphaeaceae) are used in the Indian traditional system of medicine to treat diabetes mellitus but have not been scientifically investigated. Hence, the current study was aimed to evaluate the hypoglycemic and antihyperglycemic effect on normal and alloxan-induced diabetic rats. Hydroethanol extract (HEE) of Nymphaea stellata at an oral dose of 200, 300, and 400 mg/kg was given, and blood glucose level (BGL) on normoglycemic and, diabetic rats and oral glucose tolerance test (OGTT) were evaluated. HEE of the flowers did not show significant reduction on BGL in normoglycemic rats but significantly (p < 0.001) reduced the BGL in hyperglycemic animals by improving OGTT. These results clearly show that flowers of N. stellata do not have hypoglycemic activity in normoglycemic rats but have an antihyperglycemic activity in alloxan-induced diabetic rats.     

Physician perceptions of GLP-1 receptor agonists in the UK

Objectives Glucagon-like peptide-1 (GLP-1) receptor agonists have been used to treat type 2 diabetes for almost a decade, and new treatments in this class have recently been introduced. The purpose of this study was to examine perceptions of GLP-1 receptor agonists among physicians who treat patients with type 2 diabetes in the UK.

Methods A total of 670 physicians (226 diabetes specialists; 444 general practice [GP] physicians) completed a survey in 2014.

Results Almost all physicians had prescribed GLP-1 receptor agonists (95.4% total sample; 99.1% specialists; 93.5% GP), most frequently to patients whose glucose levels are not adequately controlled with oral medications (85.9% of physicians) and obese/overweight patients (83.7%). Physicians’ most common reasons for prescribing a GLP-1 receptor agonist were: associated with weight loss (65.8%), good efficacy (55.7%), less hypoglycemia risk than insulin (55.2%), not associated with weight gain (34.5%), and better efficacy than oral medications (32.7%). Factors that most commonly cause hesitation when prescribing this class were: not considered first line therapy according to guidelines (56.9%), injectable administration (44.6%), cost (36.7%), gastrointestinal side effects (33.4%), and risk of pancreatitis (26.7%). Almost all specialists (99.1%) believed they had sufficient knowledge to prescribe a GLP-1 receptor agonist, compared with 76.1% of GPs.

Conclusions Results highlight the widespread use of GLP-1 receptor agonists for treatment of type 2 diabetes in the UK. However, almost a quarter of GPs reported that they do not have enough knowledge to prescribe GLP-1s, suggesting a need for increased dissemination of information to targeted groups of physicians. Study limitations were that the generalizability of the clinician sample is unknown; survey questions required clinicians to select answers from multiple response options rather than generating the responses themselves; and responses to this survey conducted in 2014 do not reflect perceptions of the most recently introduced GLP-1 receptor agonists.     

Baseline characteristic differences between patients prescribed sitagliptin vs. other oral antihyperglycemic agents: analysis of a US electronic medical record database

Abstract

Aims:

This study examined the relationship of baseline characteristics and medication use in patients with type 2 diabetes who were prescribed sitagliptin versus other oral antihyperglycemic agents in clinical practice settings in the United States.     

Pharmacokinetic,pharmacodynamic and clinical evaluation of saxagliptin in type 2 diabetes

Introduction: Dipeptide peptidase-4 (DPP-4) inhibitors such as saxagliptin are established and efficacious oral therapies in the management of type 2 diabetes. These agents have the potential to confer significant benefits in glycemic control without the risk of weight gain and hypoglycemia, which may be associated with other medications used to treat type 2 diabetes.

Areas covered: This review examines the pharmacokinetics, efficacy and tolerability of saxagliptin for the management of type 2 diabetes.

Expert opinion: Saxagliptin is routinely used in the management of type 2 diabetes as monotherapy, and in combination with other oral agents and insulin. Robust clinical trials have shown consistent improvements in glycated hemoglobin, fasting and postprandial glucose levels, with few adverse effects. The agent is well tolerated with low rates of hypoglycemia in the absence of insulin or sulphonylurea therapy.     

Antihyperglycemic Activity of the Aqueous Stem Extract of Coscinium fenestratum. in Non–insulin Dependent Diabetic Rats

Abstract

The antihyperglycemic potential of the aqueous stem extract of Coscinium fenestratum. Colebr. (Menispermaceae), a medicinal plant widely used in traditional Ayurveda and Siddha systems of medicine for the treatment of diabetes mellitus, was evaluated in the streptozotocin-nicotinamide–induced type 2 diabetic model. Graded doses of the aqueous stem extract were administered to normal and experimental diabetic rats for 12 days. In extract-treated diabetic rats, an insulin-independent action with significant reduction in blood glucose, serum triglyceride, and cholesterol levels was observed. In addition, other parameters like change in body weight, thiobarbituric acid reactive substance levels, glycosylated hemoglobin and liver glycogen levels, assessed in the extract-treated diabetic rats, were compared with diabetic control and normal animals. Significant results were observed in the above parameters thereby justifying the use of the plant in the indigenous system of medicine.     

Tyrosine kinase inhibitors as novel drugs for the treatment of diabetes

Introduction: Some inhibitors of tyrosine kinase, as imatinib, erlotinib and sunitinib have antihyperglycemic effects but the mechanisms are not totally clear.

Areas covered: It is well established that insulin resistance and beta-cell failure are hallmarks of type 2 diabetes mellitus (DM2). The present review will discuss the molecular mechanisms that account for insulin resistance and beta-cell failure in DM2, and also the effect of tyrosine kinase inhibitors in these processes.

Expert opinion: A better understanding of how these drugs improve the two most important mechanisms of DM2 associated with suggestions of clinical studies will lead to improve the treatment of this disease.     

Effect of mulberry leaf (Folium Mori) on insulin resistance via IRS-1/PI3K/Glut-4 signalling pathway in type 2 diabetes mellitus rats

Context: Folium Mori, the leaf of Morus alba L. (Moraceae), has been used in traditional Chinese medicine (TCM) for treating diabetes. However, it is unclear which components in the mulberry leaf are effective for the treatment of type 2 diabetes mellitus (T2DM).

Objective: To investigate the flavonoids and polyphenols in mulberry leaves and their antihyperglycemic and antihyperlipidemic effects in T2DM rats.

Materials and methods: Male Sprague-Dawley rats were divided into five groups: normal control (NC), diabetic control (DBC), diabetic group with 0.3?mg/kg b.w./day rosiglitazone (RSG), diabetic group with 7?g/kg b.w./day TCM formula and diabetic group with 2?g/kg b.w./day Folium Mori extract (FME). After 4 weeks, the rats were sacrificed; biochemical parameters, gene and protein expression were measured.

Results: The FBG level was significantly lower in the FME group than in the DBC group (p?<?0.05). In oral glucose tolerance test, the AUC was significantly lower in the FME group (p?<?0.05). The HOMA-IR level was significantly decreased in the FME group (p?<?0.05). FME decreased the total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) levels (p?<?0.05). FME increased the mRNA and protein expression of IRS-1, PI3K p85α and Glut-4 increased significantly (p?<?0.05). Histological analysis revealed amelioration of lipid accumulation following FME treatment. Additionally, immunohistochemical analysis displayed stronger staining of Glut-4 in the FME group compared to the DBC group.

Discussion and conclusion: FME could decrease the body weight, blood glucose, TG, TC and LDL levels, and improve insulin resistance. FME possessed significant antihyperglycemic and antihyperlipidemic activities via the IRS-1/PI3K/Glut-4 signalling pathway.     

Treatment options for paediatric diabetes

Importance of the field: Diabetes mellitus is the most common endocrine disease in childhood. The global incidence of diabetes emphasizes the health, social and financial magnitude of this disease and the importance of optimizing disease management and prevention.

Areas covered in this review: This article reviews the treatments options for type 1 and 2 diabetes in children, focusing on insulin regimens and new alternative therapies.

What the reader will gain: The treatment goals for children with diabetes mellitus are to achieve normal development with prevention of complications. Insulin is the primary medication in the treatment of type 1 diabetes. New therapeutic options and prevention strategies (cellular therapies, immunomodulation and vaccination) aim to preserve residual beta-cell function. There are limited data about the effectiveness and safety of treatment strategies for type 2 diabetes. Many oral agents are approved only for use in adults and have not been yet studied in children.

Take-home message: Therapy regimens should be adapted to the lifestyle of individual patients to achieve optimal blood glucose control. The replacement of beta-cells, preservation of the residual beta-cell function and investigation of additional oral treatment options, present a hope for a cure.     

Prescription medication burden in patients with newly diagnosed diabetes: A SUrveillance,PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) study

ObjectiveTo understand the burden of medication use for patients with newly diagnosed diabetes both before and after diabetes diagnosis and to identify subpopulations of patients with newly diagnosed diabetes who face a relatively high drug burden.DesignRetrospective cohort study.Setting11 integrated health systems in the United States.Participants196,654 insured adults 20 years of age or older newly diagnosed with type 1 or type 2 diabetes from January 2005 through December 2009.Main outcome measuresNumber of unique therapeutic classes of drugs dispensed in the 12 months before and 12 months after diagnosis of diabetes in five categories: overall, antihypertensive agents, antihyperlipidemic agents, mental health agents, and antihyperglycemic agents (in the postdiagnosis period only).ResultsThe mean number of drug classes used by newly diagnosed patients with diabetes is high before diagnosis (5.0) and increases significantly afterward (6.6). Of this increase, 81% is due to antihyperglycemic initiation and increased use of medications to control hypertension and lipid levels. Multivariate analyses showed that overall drug burden after diabetes diagnosis was higher in women, older, white, and obese patients, as well as among those with higher glycosylated hemoglobin concentrations and comorbidity levels (significant for all comparisons). The overall number of drug classes used by newly diagnosed patients with diabetes after diagnosis decreased slightly but significantly between 2005 and 2009.ConclusionPatients newly diagnosed with diabetes face a substantially increased burden of medications used to control diabetes and other comorbidities. This study shows an increased focus on cardiovascular disease risk factor control after diagnosis of diabetes. However, total drug burden may be slightly decreasing over time.